Introduction to Histopathology

Bela Szende and Zsuzsanna Suba

Introduction
to Histopathology
Bela Szende and Zsuzsanna Suba

M ED I CINA P U BLISHING co., B U DAPEST, 1999

O rigi nal H u ngarian Title:

Bevezetes a hisztopatol6giiiba

Bela Szende a n d Zsuzsa n n a S u ba , 1998

ISBN 963 242 509 X

Respo n s i b l e for p u b l i s h i n g : d i rector of Med i c i n a Pu b l i s h i ng House Co.

Typographer: Zoltan Szasz

S ize : 20,5 (N5) sheets - Nu m ber of figures : 246
Ide ntity No . : 1523
Typeset by abc stud i 6 , Szeged
Printed in Hungary
Szechenyi Printing House - Gy6r 98.
Director: Ivan Nagy

Contents

Preface t o the First Edition ................................... .

Preface to the Second Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
Translator's Note .......................................... .
A Guide to the Examination and Interpretation of Histologic Sections ....... .
General Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Degeneration
1 . Vacuolar degen e ratio n of renal t u b u lar epithel i u m
2 . Fatty degenerati o n of the l iver . . . . . . . . . . . . . .
3 . Renal amyl o i dosis . . . . . . . . . . . . . . . . . . . . . . .
Storage D iseases
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4. Liver i n Niel]a n n -pick disease . . . . . . . . . . . . . .
" 5 . B ra i n i n Tay-'S iiCh s-Schaffer disease . . . . . . . . . . .
Pigmentation and Metabolic D iseases.
6. C h ro n i c passive congestion of l u n g . . . . . . . . . .
7. Hepatic hemosiderosis . . . . . . . . . . . . . . . . . . .
8. H epatic cholestasi s . . . . . . . . . . . . . . . . . . . . . .
9. Pigmented nevus . . . . . . . . . . . . . . . . . . . . . . .
Atrophy
1 0. P u l monary e m p hysema . . . . . . . . . . . . . . . . . . .
1 1 . Polycystic k i dn ey disease . . . . . . . . . . . . . . . . . .
1 2 . Testicu lar atrophy . . . . . . . . . . . . . . . . . . . . . . .
Necrosis
1 3 . Anemic i n farct of k i dn ey . . . . . . . . . . . . . . . . . .
1 4. Hemorrhagic i n farct of l u n g . . . . . . . . . . . . . . . .
1 5 . Ischemic i n farct of b ra i n . . . . . . . . . . . . . . . . . .
1 6 . Centrilobular necro s i s of l iver . . . . . . . . . . . . . .
Hyperplasia
17. S i mp l e hyperpl asia of e n do m etri u m . . . . . . . . . .
1 8 . Nodu lar hyperplasia of p rostate . . . . . . . . . . . . .
Hemodynamic Disorders
1 9 . P u l m o n ary edema . . . . . . . . . . . . . . . . . . . . . .
20. T h rombosis . . . . . . . . . . . . . . . . . . . . . . . . . . .
I nflammation
21 . F i b r i n o u s pericarditis . . . . . . . . . . . . . . . . . . . .
22. P u l monary and cerebral abscess . . . . . . . . . . . . .
23. Cervicofacial act i n omycosis . . . . . . . . . . . . . . . .
24. M i l iary t u b e rcu losis i n l u n g . . . . . . . . . . . . . . . .
25. Tubercu l o u s lymphadenitis . . . . . . . . . . . . . . . .

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26. Mycobacteri u m tubercu losis . .

27. Candidal esophagitis . . . . . . . .
G ra n u lation and Wou n d H ea l i n g
2 8 . G ra n u loma . . . . . . . . . . . . . .
29. Peri pheral giant cel l gran u loma
30. Wo u n d h ea l i n g by fi rst i ntention

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Neoplasms

Epithel ial Neoplasms

31 . Verruca v u l garis . . . . . . . . . . . . . . . . . . . . . . . . . .
32. M o l l u s c u m contagi o s u m . . . . . . . . . . . . . . . . . . . .
33. S q u a m o u s cel l papi l loma of larynx . . . . . . . . . . . . .
34. Sq uamous cel l carc i n o m a of l u n g . . . . . . . . . . . . . .
35 . Basal cel l carcinoma of s k i n . . . . . . . . . . . . . . . . . .
36. Adenocarci noma of colon . . . . . . . . . . . . . . . . . . .
37. Cystadenocarc i n o m a of ovary . . . . . . . . . . . . . . . . .
38. I nvasive ductal carci n o m a of b reast . . . . . . . . . . . . .
39. Metastatic carci n o m a i n lym p h n ode . . . . . . . . . . . .
40. Tumor ce l l s i n p l e u ral f l u i d . . . . . . . . . . . . . . . . . .
Mesenchymal Neoplasms
41 . Myxo ma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42 . Capi l l a ry hemangioma and cavernous hemangioma . .
43. Uterine l e i o myoma . . . . . . . . . . . . . . . . . . . . . . . .
44. Rhabdo myosarcoma . . . . . . . . . . . . . . . . . . . . . . .
45 . C h o n drosarcoma . . . . . . . . . . . . . . . . . . . . . . . . .
M ixed T u m o rs
46. Pleomorph i c adenoma (m ixed t u m o r) of paroti d gland
47. W i l ms' t u m o r ( n e p h roblastom a) . . . . . . . . . . . . . . .
Other Neoplasms
48 . Mal i gnant melanoma . . . . . . . . . . . . . . . . . . . . . .
49 . Choriocarci noma . . . . . . . . . . . . . . . . . . . . . . . . .
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Systemic Pathology

Cardiovascu l a r System
50. F i b ro s i s and fatty i nfi l t ratio n of myocardi u m
51 . Acute myocardial i n fa rct . . . . . . . . . . . . .
52. Rheu mat i c myocarditis . . . . . . . . . . . . . .
5 3. E n docardial f i b roelastosi s . . . . . . . . . . . . .
54. Atherosclerosis of aorta . . . . . . . . . . . . . .
5 5 . Cysti c medial necrosis of the aorta . . . . . .
56. B u e rger's disease . . . . . . . . . . . . . . . . . .
57. Periarteritis n odosa . . . . . . . . . . . . . . . . .
58. Kaposi's sarcoma . . . . . . . . . . . . . . . . .
Resp i ratory System
59. Lobar p n e u m o n i a . . . . . . . . . . . . . . . . . .
60. B ronch p n e u m o n i a . . . . . . . . . . . . . . . . .
61 . P n e u mocystis cari n i i p n e u m o n i a . . . . . . . .
62 . Hyal i n e m e m b rane disease . . . . . . . . . . .
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63. P u l monary s i l i cosis . . . . . . . . . . . . . . . . . . . . . . . .

64. B ronchoge n i c s m a l l cel l carcinoma . . . . . . . . . . . . .
65 . B ronch i o l oalveolar carc i noma . . . . . . . . . . . . . . . .
Blood and Lym phoid O rgans
66. S i n u s h i stiocytosis of lymph node . . . . . . . . . . . . . .
67. Leu ke m i c i nf i ltrate i n the l iver . . . . . . . . . . . . . . . .
68. Hodg k i n 's disease . . . . . . . . . . . . . . . . . . . . . . . .
69. Non-Hodgki n ' s lymphoma . . . . . . . . . . . . . . . . . . .
70. M u ltiple myeloma . . . . . . . . . . . . . . . . . . . . . . . .
O ral Pathology
71 . Cytomegalovi ral i n fection of paroti d gland . . . . . . .
72 . Chronic s ialade n i t i s . . . . . . . . . . . . . . . . . . . . . . .
73. Radicu lar cyst . . . . . . . . . . . . . . . . . . . . . . . . . . .
74. Benign Iymphoepithel ial lesion . . . . . . . . . . . . . . .
75. O ral l e u koplakia . . . . . . . . . . . . . . . . . . . . . . . . .
76. G ra n u lar cel l t u m o r . . . . . . . . . . . . . . . . . . . . . . .
77. Ameloblastoma . . . . . . . . . . . . . . . . . . . . . . . . . .
78. Warth i n 's t u m o r . . . . . . . . . . . . . . . . . . . . . . . . . .
79. Adenoid cystic carci noma . . . . . . . . . . . . . . . . . . .
Gastroi ntesti nal Tract
80. Chronic gastritis . . . . . . . . . . . . . . . . . . . . . . . . . .
81 . Chronic peptic u l cer . . . . . . . . . . . . . . . . . . . . . . .
82. I ntram ucosal carci noma of sto mach . . . . . . . . . . . .
83. M u c i n o u s adenocarcinoma of stomach . . . . . . . . . .
84. Regional enteriti s (Cro h n ' s disease) . . . . . . . . . . . .
85 . Acute appe n dicitis . . . . . . . . . . . . . . . . . . . . . . . .
86. Enterobi u s vermicu laris i n appendix . . . . . . . . . . . .
87. U lcerative col itis . . . . . . . . . . . . . . . . . . . . . . . . .
88. Tubular adenoma of colon . . . . . . . . . . . . . . . . . .
Liver and B i l iary Tract
89. Acute vi ral hepatitis . . . . . . . . . . . . . . . . . . . . . . .
90. Chronic hepatitis . . . . . . . . . . . . . . . . . . . . . . . . .
91 . Alco h o l i c hepatitis . . . . . . . . . . . . . . . . . . . . . . . .
92 . M icronodular ci rrhosis . . . . . . . . . . . . . . . . . . . . .
93. Hepatoce l l u lar carcinoma . . . . . . . . . . . . . . . . . . .
Kidney and Uri nary Tract
94. Benign nephrosclero s i s . . . . . . . . . . . . . . . . . . . . .
95. Acute diffuse p ro l i ferative glomeru l o n eph ritis . . . . .
96. Mem branoprol ife rative glomerulonephritis . . . . . . .
97. Chronic pye l o n ep h ritis . . . . . . . . . . . . . . . . . . . . .
98. D iabetic glomeru l o pathy . . . . . . . . . . . . . . . . . . . .
99. Renal tuberc u l o s i s . . . . . . . . . . . . . . . . . . . . . . . .
1 00 . End-stage renal disease . . . . . . . . . . . . . . . . . . . . .
1 01 . Renal cel l carc i n oma . . . . . . . . . . . . . . . . . . . . . . .
1 02 . Pap i l lary tran sitional ce l l carci noma o f u ri nary b ladder

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Male Reproductive System

1 03. Seminoma
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1 04 . E m b ryonal carc i n o m a of testis .
1 05 . Adenocarc i n oma of p rostate . . . . . . . . . . . . . . . . . . . . .
Female Reproductive System and B reast
1 06 . Pregnancy . .
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1 07 . Hydat i diform mole . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 08 . E rosion and pse u doerosion of uterine cervix . .
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1 09 . S q u am o u s cel l carcinoma of ute r i n e cervix . . . . . . . . . . .
1 1 0 . Sero u s and m u c i n o u s cystadenomas of ovary . . . . . . . . . .
1 1 1 . G ran u losa-theca cel l t u m o r of ovary . . . . . . . . . . . . . . . .
1 1 2 . F i b rocystic disease of b reast . . . . . . . . . . . . . . . . . . . . . .
1 1 3. F i b roadenoma of b reast . . . . . . . . . . . . . . . . . . . . . . . . .
1 1 4 . Paget's disease of n i pp l e
Bones
1 1 5 . Paget's disease of bone . . . . . . . . . . . . . . . . . . . . . . . . .
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1 1 6. C h o n droma
1 1 7. Osteosarcoma . .
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Endocri ne System
1 1 8 . Nodu lar goiter
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1 1 9 . P r i mary thyro i d hyperp lasia (G raves' disease)
1 20 . S u bacute gra n u l omatou s thyro i ditis of De Q u e rvai n
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1 21 . Pap i l lary adenocarcinoma of thyro i d gland . . . . . . . . . . .
1 22 . Adrenal cortical adenoma . . . . . . . . . . . . . . . . . . . . . . .
Nervo u s System
1 23. Postvacc i n al encephalomye l itis . . . . . . . . . . . . . . . . . . .
1 24 . Acute p u ru lent m e n i ngitis
1 25 . Men i n gioma
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1 26 . Astrocyto ma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 27 . Ne u roblasto ma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 28 . G l ioblastom a m u ltiforme . . . . . . . . . . . . . . . . . . . . . . . .
1 29 . Schwa n n o m a
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Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
I m m u n o h i stochemistry
I m m u no h i stochem ical diffe rentiation o f t u m o rs of mesenchymal
I.
and m u scular origin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 1. Amelan otic fo rm of mal ignant melanoma diagnosed with
i m m u n o h i stochem ical methods . . . . . . . . . . . . . . . . . . . . . . . .
I ll . I m m u no h i stoc h e m i cal reactions i dentifyi ng mal ignant tumor
as epithelial a n d of p rostatic origin
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I V . Diagnosis and s u btypi n g of malignant lymphomas with
i m m u no h i stochemical methods . . . . . . . . . . . . . . . . . . . . . . . . .
V . I m m u no h i stochem ical dem o n stration of estrogen and p rogeste ro ne
receptor p rote i n s in carci noma of the b reast . . . . . . . . . . . . . . .
B i b l i ography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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287

Preface to the Fi rst Ed ition

The primary aim o f t h i s book i s t o p rovide gu idance i n t h e study of h istologic

sl ides of the pathol ogy co u rse. For this reason we are fol lowi ng the o u t l ines of the
pathology co u rse; the topic is divided into two parts , a general and a special patholo
gy sectio n . The book also p resents exam ples of h i stologic s l ides which are part of
the pathology cou rse fo r medical and dental stu dents. We are introduc i n g
pathologic entities which a r e characteristic and shou l d assist i n m o re effective learn
ing of the theoretical part of the cou rse. H owever, space does not permit the p resen
tation of many im portant lesio n s .
The explanatory text i n c l u des t h e defin ition o f i n dividual pathologic entities, a
brief description of the gross findings fol lowed by an analysis of the m icroscopic
changes, sometimes i n greater detail than seen o n the m icrophotograph s . Where
needed, m icrophotos of lower and h igher mag n ification have been p rovided. Beside
the standard hematoxy l i n -eosin stain we have u sed, where particu larly h e l pfu l , spe
cial stains. For better orientatio n , certa i n m icroscopic struct u res have been pointed
out by lette rs . We hope that t h is book wil l accom p l is h its goal and wi l l not o n l y
gu ide t h e stu dents i n their laboratory cou rse but w i l l also s u pplement the pathology
textbook.
At this place we thank Ms. E. Val6czy and Mrs. B . Baj usz fo r the p reparation of the
h isto l ogic s l i des. We gratef u l ly acknowl edge the h e l p of D r . T . Marton and Ms. Z.
Nemes i n the p reparation of the man u script for p u b l icatio n .
T h e Authors

Preface to the Second Ed ition

The fi rst edition of " I ntroduction t o H i stopathology" was wel l received a n d con
t i n u o u s demand for a book of this type has become evident. When Medici n a Pub
l ishers p roposed a new, e n l arged editi o n , the opport u n ity arose fo r a revised and
expanded boo k .
Because o f the great p rogress i n pathology, w e h ave i ntroduced some i m m u nohis
tochemi cal stai ns in an Appendix. These stai ns h ave becom e i n di spensab le today fo r
the p ract i c i n g patho l ogist.
We reco m m e n d this e n l arged edition m ai n ly to medical students and to you n g
pathologi sts i n trai n i n g .
B. S . , Z. S .

10

Translator's Note

Medical texts are rel atively straightforward and can be read i ly tran s l ated .
Nevertheless, d i fferences i n nomenclatu re and sometimes i n c l assifi catio n of d i s
eases have to be taken i nto consideratio n . The H u n garian text (2nd edition) was
translated u s i n g cu rrent American med ical terms. Whereve r feas i b l e , the Lat i n d i ag
noses were retai ned and i n d i cated in parentheses, in o rd e r to h e l p students fam i l i ar
with the classical term i no l ogy. Eponyms and tech n ical terms com mo n l y u sed i n
E u rope also h ave been mento i ned, e . g . , G raves' ( Basedow's) d i sease. The ai m h as
been to p reserve the l ucid ity of the orig i n al text and to avoi d am b i g u ities i n the
translatio n . Hopefu l ly , en deavo u rs of this kind wi l l contri b ute to the real ization of
o u r common goal , better health care in every cou ntry.

11

A Gu ide to the Exam ination

and I nterpretation of Histologic Sections

I t i s u sefu l at fi rst t o scan a m icroscopic s l i de u n de r l ow m agnification an d t o look

for n o rm al tissue (if p resent) . The extent and borders of the patho logic process
s h o u l d also be assessed u n de r low power. The i nvolved cel l popu l ation an d its
cytopatho logic feat u res can be exam i ned u n de r h i gher m agn ification . H i gh magnifi
cation i s n eeded to i dentify m i c roo rgan is m s .
H i sto logic s l i des can be studied w i t h n u mero u s stai n i n g tech n i q u es . With t h e most
bas i c an d routi nely e m p loyed hematoxyl i n-eosi n stai n cel l n uclei , m u ci n , calcifi ca
tion and m icroo rgan i s m s appear dark b l u e , the cyto p l as m of cel l s , hyal i n , kerat i n ,
necrotic t i s s u e , etc . , appear red. Special methods are u sed t o demon strate certain
s u bstances, e. g. l i p i ds are stai ned with O i l red 0 (on frozen sections), amyloid is
stai ned with Congo red, i ro n -contai n i ng pigme nts are i dentified with Perls' Prussian
b l u e reactio n . Certai n p athogens ( e . g. Act i n omyces israe l i i , Candida al bicans) stai n
m agenta red with the periodic acid-Schiff (PAS) reaction . Mycobacteri u m tuber
culosis is dem o n strated with the Ziehl-Neelsen method. Connective tissue can be
diffe rentiated from m uscle an d epithel i u m , respectively, with a tri chrome stain such
as Mal l o ry's, H e i de n h ai n ' s " azan " ( Azo karm i n B an d Ani l i n b lau W) , Endes' etc. modi
ficat i o n s . E l astic fibers can be demonstrated with Van G i eson's elasti n stai n , which is
h e l pfu l in the study of vascu l ar diseases. Other, less often u sed stai n i ng methods
are i ntroduced when employed.
In the Appe n dix we p resent some of the m o re i m portant i m m u no h i stochemical
stai n s . These demonstrate special components of cel l s and may be helpful diagnostic
tool s .

12

GENERAL PATHOLOGY

1. Vacuolar degeneration of renal tubular epithelium

(DEG E N E RATI O VACU O LARIS REN I S)
H e m atoxyl i n-eosi n
The distu rbance of e lectrolyte an d water metabolism of cel ls p l ays an i m portant
rol e i n the development of vac u o l ar degene ration of cel l s . The chan ges are most
conspicuous i n the epithel i al cel l s of the ren al t u b u les. They m ay be associ ated with
diseases of the gastro- i ntesti n al tract which cause significant loss of water an d potas
s i u m (e. g. dysente ry, u lce rative co l itis) . Con n ' s syndrome, hypoxi a or poi so n i ng
(e. g. diethylene glyco l ) , i nt rave n o u s mann itol i nf u s i o n m ay cau se s i m i l ar damage.
If the i n j u ri o u s i nfl u ence ceases an d h as n ot cau sed profo u n d alterations i n the
chemical composition and in the f i n e structu res ( m e m b ranes an d organ e l l es) of the
cel l s , then the t u b u l ar vac u o l ation is reversi b l e .
Gross Findings. The k i dn eys appear swo l l e n , thei r co rtex i s widened, pale b rown .
The pyram i ds of the medu l l a show dusky streaks as a res u l t of passive congesti o n .
Microscopic Findings. S i gn ifi cant ch anges are s e e n i n the renal cortex, mai n ly i n the
epithel i u m of the p ro x i m al convo l u ted t u b u les. The epith e l i al cel l s are swo l l e n , de
fo rmed and the i r cyto p l as m contai n s a l arge, e m pty appear i n g vacuole which pu shes
the n uc l e u s asi de , thus making the cel l s ig n et-ring l i ke . The res i du al thin rim of
cytop l as m is pale and eosi noph i l ic . The vacuoles do not contai n l i p i d, glycogen or
othe r s u bstances, they are f i l l e d with t h i n f l u id. The n uclei of the epithel i al cel l s
retai n the i r stai n i n g . Sometimes a hydropic vacuole a l s o can b e seen i n t h e n u cleus.
In cases of severe vac u o l ar degene ration the p l as m al e m m a of the m arkedly swo l l en
cel l r u ptu res and the cel l dies .
Electron microscopic examination demonstrates that the l arge i ntracytop l asmic va
cuo les are bordered by a s i m p l e m e m b rane and they correspon d to a h uge p i nocyto
t i c vacuole.

14

Fig. 1 . N

n u cleu s ; C

cytoplasm ; V

vacuole

2 . Fatty degeneration of the l iver

(STEATOS I S H EPATIS, DEG E N E RAT I O AD I POSA H EPATIS)
H e m atoxy l i n-eo s i n , O i l red 0
Li p i d m ay accu m u l ate i n l iver cel ls if an excessive amo unt of fat is to be
metabol ized (as i n overeat i n g) or if the f u n ction of the l iver cel l s is i m p ai red. The
l atter mechan i s m accou nts for fatty degene ration due to hypoxia, toxic damage (al
coh o l , c h lorofo r m , carbon tetrac h l o r i de , arsenic etc. ) o r certain i nfectious diseases.
Gross findings. The l iver i s e n l arged, has a smooth s u rface, tense capsule an d
ro u n ded edges. Its parenchyma is soil, yel lowis h ; the cut s u rface is greasy an d the
l o b u l ar arch itect u re i s i n disti n ct .
Microscopic findings. T h e damage m ay be focal; i n s u c h cases gro u ps o f fatty l ive r
cel l s are i rregu l arly distributed, i n dependent of the l o b u l ar architect u re . Zonal fatty
changes occ u r i n al l lobu les, diffusely affecti n g the same zone. I n this category we
recogn ize centrilobular steatosis, i n which the fatty degeneration occu rs i n the l iver
cel l s aro u n d the central vei n s . T h i s type of zonal steatosis freq u ently develops as a
res u l t of c h ro n ic hypoxi a. Midzonal an d peripheral lobularfatty degeneration is seen
in poison i ng (phosphorus) o r in yel l ow feve r; in such cases the m i d-zonal an d
peri pheral l o b u l ar hepatocytes, respectively, are damaged. I n the early phase of
fatty degenerat i o n , vacuoles appear i n the cytop l asm aro u n d the n ucleus; because
thei r l i pi d content i s dissolved in the cou rse of em beddi ng. The vacuoles appear
e m pty. As the damage to the cel ls p rogresses, the hepatocytes become swo l l en an d
a s i ngle l arge vac u o l e wi l l occu py thei r e nti re cytop l as m , p u s h i n g asi de the n u cleus
an d making the hepatocyte s ignet-ring shaped. The degenerated hepatocytes form
wide trabecu l ae which com p ress and n arrow the l u me n of the s i n u so i ds . The fat can
m icroscopi cal ly be v i s u al ized on frozen sections with one of several special stai ns
( S u dan I l l , S u dan IV, osm i u m tetroxide, N i l e blue s u l fate, Oil red 0) .

16

Fig. 2. Top: He matoxylin-eosin; Bottom: O i l red O.

C - central vein; V - vacuole; H - intact hepatocyte; L l i pid droplets .
-

L
c

3 . Renal amyloidosis
(AMYLO I DOSIS R E N I S)
H e m atoxyl i n -eos i n , Co n g o red
Amyl o i d i s a generic des i g n ation of a ch aracte ristic p rote i n aceou s deposit i n the
i n terstit i u m of o rgans an d tissues. Various amyl oid p rote i n s exist, their common
components i n c l u de glycosam i noglycans and p roteoglycan s . Several diseases
c h aracterized by necro s i s of tissues or destruction of p rote i n s (e.g. chronic os
teomye l itis, tu bercu losis, cachex i a due to neoplasms, etc . ) can be associated with
system i c amylo i dos i s . Advanced amyl o i dosis of the k i dneys can lead to renal i n suffi
ciency.
Gross Findings. In ren al amy l o i do s i s the ki dneys are l arge, pale, tan to yel low, feel
stiff. The cortex i s con s i de rably swo l l e n , w i dened an d on cut s u rface it appears waxy;
on t h i n sections it h as a g l assy trans l u cency.
Microscopic Findings. Amyl o i d appears as an eos i nop h i l i c homogeneo u s ace l l u l ar
s u bstance, w h i ch affects m ai n ly the glomeruli. Amy l o i d deposits u n der the en
dothel i u m of the loops of the glome r u l u s and causes an i rregu l ar thicke n i ng of the
basement membrane. Becau se of the s i m u ltaneous deposition of amyloid, the
mesangium becomes widened an d homogeneo u s l y eosi noph i l i c . As this process
p rogresses the cap i l l ary wal l s t h i cken an d t h e i r l u men n arrows; eventually the
glomeru l u s is no l o n ge r perfu sed, its cel l u l ar components disappear an d it becomes
rep l aced by b u n dles of homogeneous eos i noph i l i c amyl o i d. I n the cortex an d in the
medu l l a the small arteries and arterioles become thicker due to deposits of amyl oid
wit h i n the i r wal l an d stai n homogeneously eos i n o p h i l i c . In advanced cases deposits
of amyl o i d can also be observed in the basement membrane of the renal tubules an d
i n the interstitium along the co n nective tissue fi bers . Amy l o i d can be demo nstrated
m icroscop ical l y with speci al stai n s . Congo red (bottom , left) metac h romatical ly
stai n s amyl o i d a vivid o range, wh i l e the u n i nvolved areas are pale yel l ow. The pre
sence of amy l o i d can be verified with pol arized l i ght, s i nce amy l o i d deposits stai ned
with Congo red give an apple-green b i refri ngence (bottom , right) .

18

Fig. 3. Top : Hematoxy l i n-eos i n ;

Bottom left : Congo red ;
Bottom right: same field u nder polarized l i ght.
G - glomeru l u s ; M mesangi u m ; A - artery; T - t u b u les.
-

G
M

4.

Liver in Niemann-Pick disease

(MORBUS NIEMANN-PICK)

Hematoxylin-eosin, Woeleke's myelin

Niemann-Pick disease is a recessively hereditary disease due to an inborn error of
metabolism, namely the lack or reduced activity of an enzyme, sphingomyelinase.
Characteristically, sphingomyelin accumulates throughout the body in the cells of
the reticuloendothelial system, in the parenchymal cells and in the ganglion cells of
the central nervous system. Its most severe, infantile form, damages the nervous
system and causes early death.
Gross Findings. The liver is moderately enlarged, pale red to yellow. On cut surface
its lobular architecture is indistinct.
Microscopic Findings. The lobular architecture of the liver is recognizable. Swollen
hepatocytes with small, round, eccentric nuclei can be seen scattered or in larger
groups in parenchyma. The volume of the swollen cells is several times that of nor
mal hepatocytes, their cytoplasm is faintly eosinophilic and has a foamy appearance
due to small vacuoles. Some cells have larger cytoplasmic vacuoles which were left
by dissolved lipid droplets. The affected hepatocytes are aligned in deformed cords
which compress the lumen of the sinuses. Similar changes suggestive of an abnormal
lipid content are also seen in the Kupffer cells and in the epithelium of the bile
ducts. On frozen sections stained for sphingomyelin the foam cells give a positive
reaction.

20

Fig. 4. Top: Hematoxylin-eosin;

Bottom: Woelcke's myelin stain.
H - normal hepatocytes; L - lipid-laden hepatocytes.

5 . B rain i n Tay-Sachs-Schaffer disease

( I DI OTIA AMA U ROT I CA FAMILlAR I S)
H em atoxyl i n -eos i n , O i l red 0
T h i s disease i s o n e of several h ereditary diso rders characterized by accu m u l ation
of abn o r m al l i p i ds . The acc u m u l ation of G M2 gan g l i os i de with i n the gan g l i o n cel l s
of the central n e rvo u s sytem , i ncluding t h e ret i n a as wel l as other o rgans ( heart,
l iver, spleen), occ u rs as a resu lt of deficiency of the aci d hydrol ase, hexosam i n i dase
A. These c h anges cause b l i n dn ess and severe m e ntal retardation . The patients die
in the i r i nfancy, at ages 1 -2 years.
Gross Findings. The vol u me of the b rai n i s s i g n ificantly i n creased, u p to 50% . The
gyri are widened an d the su lci n arrowed. The b rainstem and cerebe l l u m are atrophic.
Microscopic Findings. The gan g l i o n cel l s of the cereb ral co rtex are bal loo n i ng. I n
paraff i n embedded tissue the cyto p l as m of some cel l s contai n s s m al l , empty appear
i n g vac u o l es , which are the s ites of dissolved l i p i ds . The stored l i p i ds can be visual
i z e d i n frozen sections stai ned with O i l r e d O . As a resu lt of the conti n u o u s acc u m u
l ation o f G M2 gangl i o s i de the cel ls of the n e rvo u s system are damaged a n d l ater
destroyed. The n uclear c h ro mati n of the dyi n g cel l s u n dergoes karyolysis an d no
l o n ge r stai n s . The l i p i d escap i n g the destroyed n e u ro n s i s removed by phagocytes
( l i pi d-l aden cel l s) . S i m u ltaneous to the disappearance of the neu rons there is a pro
l i feration of m ic rog l i al cel l s and g l i al scars wi l l devel o p .

22

swo l len ganglion c e l l s ; P

Fig. 5 . Top : H ematoxyli n-eosi n .

d i sappearing damaged neuron .
Bottom : O i l red o.
L l i p i d droplets .
-

6. Chronic passive congestion of lung

(lNDU RATIO B R U N EA PULMO N I S)
H e m atoxyl i n -eo s i n , Prus s i a n blue react i o n
C h ro n i c passive co ngestion o f the l u n g is a serious con dition ; most often m itral
ste nosis and/o r i n s ufficiency causes sign ifi cant congestion i n the p u l mon ary c i rc u l a
tion .
Gross Findings. The l u n gs are e n l arged, feel co n s i de rab ly firmer and are tan to
rusty b rown . Copio u s amou nts of frothy reddi s h b rown fl u i d can be expressed from
t h e i r cut s u rface .
Microscopic Findings. Evi dence of m arked passive congestion can be observed i n
the l u n g parenchyma. The i n te ralveol ar septa are widened, the cap i l laries are dis
ten ded with den sely p acked red blood cel l s . F l u i d leak i n g from the cap i l l aries ac
c u m u l ates i n the septa and there is an i n crease i n con n ective tissue fibers. Red
blood cel l s pass t h ro u gh the wal l of the disten ded cap i l l aries i nto the i n te rstiti u m ,
res u l t i n g i n small foci of i nterstitial hemo rrhage. The disi ntegrat i n g eryth rocytes also
get i nto the alveolar l u men where they are p h agocytized by cel l s m i g rati n g from the
alveolar septa. These alveol ar m acrophages are l arge, ro u n d o r polygonal cel ls with
ro u n d n uclei an d am p l e cytop l as m which contai ns fine o r coarser tan to brown
gran u l es of hemosideri n . This i ron-contai n i ng pigment stai n s dark b l u e with the
Pruss i an b l u e reacti o n . T h ro u g h the b ro n c h i the hemoside r i n - I aden phagocytes may
get i nto the s p u t u m of patients with p rotracted congestive heart fai l u re, an d calor it
b rown ; the refore, they are referred to as " heart-fai l u re ce l l s " . H emosiderin-Iaden
m acrophages can also be observed i n the i nteralveol ar septa and p u l mo n ary Iym
phatics.

24

Fig. 6. Top : Hematoxy l i n -eos i n ; Bottom : Prussian blue reacti o n .

i nteralveolar sept u m ; L alveolar l u me n ; P h - alveolar p h agocytes ;
H - hemosiderin depos its.
-

7. H epatic hemosiderosis
( HAEM OSIDEROSIS H EPAT IS)
Prus s i a n blue reacti o n
H emosiderosis, the acc u m u l ation of hemoside ri n , i s due to destruction of red
b lood cel l s . Excessive hemoside r i n deposits in parenchymal cel l s m ay lead in the
long run to cel l i n j u ry . Generalized hemoside rosis can devel o p in severe chro n i c
passive congest i o n , o r i n protracted hemo lytic conditions ( h em olytic anem i as, seps i s
d u e t o hemolytic streptococcu s , poiso n s) . An i atroge n i c fo rm of hemoside rosis can
occ u r after m u lt i p l e blood transfusions which l ead to the deposition of large
amo u nts of hemoside ri n .
Gross Findings. The l iver i s mode rately e n l arged, ru sty b rown an d feel s firm.
Microscopic Findings. I ro n-contai n i n g pigment i s zonally deposited in the l iver
l o b u l es . As a consequence of severe passive congestion around the central veins, the
adj ace nt s i n u ses are q u ite disten ded with b lood; here an i ncreased dis i n tegration of
eryth rocytes an d deposition of hemosideri n can be see n . I n case of hemolysis the
periphery of the lobulest i . e. the periportal hepatocytes, meet with l arger amou nts
of damaged e ryth rocytes ; co nsequently, it is here t h at sign ificant amou nts of
hemo s i deri n are deposited. I n sections stai ned with hematoxy l i n-eo s i n hemosiderin
appears in its n atu ral , gol den b rown col o r . The i ron contai n i ng pigment stai ns deep
b l u e with the Prussian b l u e reaction . Deep b l u e gran u les i n dicate the accu m u l ated
deposits of hemoside r i n in the cytop l as m of hepatocytes . S i m i l ar pigment gran u les
can also be seen in the ste l l ate Ku pffer cel l s which are p h agocytic an d l i ne the
s i n u so i ds . I n cases of l o n g-stan di n g hemosiderosis one m ay observe coarse gran u l es
of hemosideri n extracel l u l arly, m ai n ly i n the peri portal connective tissue.

26

Fig. 7. Prussian blue react i o n .

V - central vei n ; H hepatocyte; P - pigment.
-

8. H epatic cholestasis
(CH O L ESTASI S H EPAT I S)
H e m atoxy l i n -eos i n
Cholestas i s co n n otes a distu rbance i n the n o rm al b i l e secretory mechan i s m s ac
companied by acc u m u l ation of b i l e i n the l iver. S i m u ltaneously the serum level of
b i l e p i gments becomes elevated and causes jau n dice (icterus) . Hepatocellular ic
terus (i ntrahepatic cholestas i s) is see n , most often i n vi ral hepatitis or p rovoked by
drugs, alco hol or othe r toxic s u b stan ce s . Obstructive (mechanical) icterus occ u rs
when the extrahepatic b i l e ducts are obstructed by a sto ne, tumor or cicatrical stric
ture.
Gross Findings. The cholestatic l iver i s swo l l e n , i t s free edges are rou n ded, an d it
i s tan to b rown o r yel lowish-gree n . I n prolonged obstructive j au n dice the l ive r i s
dark green and on i t s cut s u rface the di l ated l arger b i l e ducts are p rom i n ently dis
tended.
Microscopic Findings. H e p atoce l l u l ar i cterus ( i ntrah epatic chol estasis) u s u al ly can
be di st i n g u i s hed from obstructive (mechan ical) icterus, which is of great i m portance
in estab l i s h i n g the correct diagnosis i n l iver biopsies. I n hepatocellular icterus the
most m arked c h anges are seen in the center of the lobu les, where the bile flow is
the s l owest . H ere the swo l l e n hepatocytes h ave a f l u ffy cytop l asm which is stai ned
yel low to b rown by cholestas i s . The acc u m u l ated b i l e fo rms yel l ow to green fine
gran u les and c l u mps in the cytop l asm of the hepatocytes . S i m i l ar bile pigment can
be observed i n the cytop l as m of the Kupffer cells. The b i l e canal icu l i are markedly
di l ated by yel lowi s h green cyl i n de rs of b i l e . I n p ro l o n ged icte rus the toxic effect of
b i l e acids and r u pt u re of the disten ded bile canaliculi leads to destruction of some
hepatocytes . I n the peri portal area there i s f i b rosis and b i l e duct u l ar p ro l ife ratio n .
Mechanical obstruction of t h e m ajor b i l e ducts also l eads t o acc u m u l ation o f b i l e i n
t h e cytop l as m of hepatocytes an d i n t h e b i l e cap i l l aries, but t h e ch aracte ristic
chan ges are in the portal areas. The epithel i u m of the l arge r bile ducts becomes flat
an d thei r di l ated l u men is chock-f u l l of yel l owish green b i l e . The peri ductal con n ec
tive tissue is edem atou s and p ro l i ferating b i l e duct u l es can be recognized. Beside
the i n c rease i n f i b ro b l asts and co n n ective tissue fi bers o n e can al so observe an i n
f l am m ato ry i nfi ltrate of Iymphocytes, h i stiocytes and neutroph i l ic polymorpho n u c
lear l e u kocytes. I n p ro l onged obstruction the wal l of the disten ded b i l e ducts rup
t u res an d bile escapes i nto the con n ective tissue of the peri portal tract. The extrava
sated b i l e forms b i l e l akes which give rise to a phagocytic react i o n , occasion ally
accompanied by a foreign body giant cel l reaction .

Fig. BA . Top : Hepatoce l l u lar icterus.

bile canal i c u l u s ; H - i nj u red h epatocytes.
Fig. BB. Bottom: Mech a n i cal icte r u s .
B - portobi l i a r area ; U - bile d u cts; I
i nflam matory i n fi ltrate.

E - bile pigment; C

28

9. Pigmented nevus
( NAEVUS P I G M E N TOSUS)
H e m atoxyl i n -eo s i n
A n ev u s i s a pigmented lesion of the s k i n or a m u co u s membrane an d can be
p resent at b i rth or devel o p l ater in l ife.
Gross Findings. Nevi can be flat, c i rcu mscri bed pigmented lesions with a smooth
s u rface, or p rotruding, wart- l i ke, hairy an d someti mes pedu n c u l ated. Dependi n g on
the content of pigment they m ay vary in col o r from flesh col o r to dark brown o r
b l ac k .
Microscopic Findings. Nevi can be c l assified acco rdi n g t o the l ocation o f the tumor
( nevu s) cel l s , thus we disti n g u i s h intraepidermal, intradermal, and compound (com
plex dermoepidermal) nevi. In intraepidermal nevi the rou n ded, wel l-defined nests
of n ev u s cel l s are seated in the basal l ayers of the epiderm is, pri m arily at the tips of
the p ap i l l ae . The n evu s ce l l s produ c i n g m e l an i n (mel anocytes) are cuboidal or poly
go nal, den sely p acked cel l s . Their n uclei are rou n d an d m itotic figu res are o n ly
occas i o n al ly e ncou ntered. The cytop l asm of the t u m o r cel ls stai n s pale and co ntai ns
a fai ntly b rown i s h cloud of m e l an i n o r m o re coarsely gran u l ar dark b rown pigment.
Intradermal nevi are l i m ited to the der m i s and are composed of i s l an ds of nevus cel l s
s u rrou n ded by del i cate b u n dles of co n n ective tissue. T h e t u m o r p ro l i fe rates i n the
der m i s an d l i fts the overlyi n g atro p h i c epiderm i s above the level of the u n i nvolved
s k i n . The amo u n t of pigment in the den sely arranged u n iform cel l s varies an d
ame l anotic areas can also occ u r . Dark brown, coarse gran u les of pigment are seen
in the cytoplas m of p h agocytic h istiocytes (melanophages) an d also among the fibers
of the i nterce l l u l ar con nective tissu e . Compound (complex dermoepidermal) nevi show
h i stologic ch aracteristics of both of the above types. Prol iferat i n g nevus cel l s can be
observed in the epiderm is as wel l as i n the der m i s .

30

epi derm i s ;

derm i s ; N

Fig. 9A . Top: I ntradermal nevus.

pi losebaceous u n i t ( s k i n appendage) .
Fig. 98. Bottom : Compound nevu s .
dermal nevus cells; M mela n i n in melanophages .

nevus cel l s ; F

nests of i n traepide rmal nevus cel l s ; D

1 0. Pul monary emphysema

( EMPHYSEMA PU LMO N U M )
H e m atoxyl i n -eos i n
Em physema i s a gro u p of p u l mo n ary diseases ch aracterized by abn o rmal e n l arge
ment of the ai r spaces distal to term i n al b ronchioles with destructi on of the alveolar
wal l s . Chronic e m physema can res u l t in any con dition in which expiration is protrac
tively difficult (ch ro n i c b ronch itis, b ro n c h i al asth ma, etc . ) . Occupational abuse (e. g.
g l ass b lowi ng, w i n d i n stru ments) and constitutional o r acq u i red weakness of the
pulmonary elastic network can l i kewise lead to p u l m o n ary em physema.
Gross Findings. The l u ngs are e n l arged and do not col l apse after open i n g the chest.
Their free edges are rou n ded; the pale gray parenchyma fee l s fluffy. On p ress u re
the l u ngs give a pecu l i ar fine crac k l i n g s o u n d due to tearing of the weakened alveo
l ar wal l s . I n centr i l o b u l ar em physema the disten ded ai r spaces appear as 0.1 to 0.3
cm . small blebs an d the cut s u rface resem bles a fine honeyco m b .
Microscopic Findings. O n e sees thinning, tearing and destruction o f i nteralveol ar
septa. The po res of Ko h n are widened, coalesce an d adjacent alveol i form a common
airspace . I n stead of the po lygon al o r rou n ded alveo l i , meas u ri n g 0.15 to 0.35 m m i n
diameter, o n e f i n ds l arge r, i rreg u l arly-shaped, sacc u l ar ai r-fi l led hollow spaces, with
rem n ants of destroyed alveo l ar septa occas i o n al ly p rotruding i nto them. With prog
ressi o n of the disease the parenchyma of entire aci n i , even lobules, can disappear
to fo rm a s i ngle com m o n cavity. Most resistant to this destructive p rocess are the
blood vessels and b ronch i ; they span the e n l arged ai rspaces as b ranch i n g b u ndles.
In overexpan s i o n thei r l u me n becomes o b l i te rated, they ruptu re an d their stumps
u n dergo atrophy. The q u antity of e l astic fi bers di m i n ishes, the i r rem n ants are t h i n
ner and fragmented.

32

Fig. 10. A

i ntact alveol i ; K

anth racotic pigment; E emphysematous ai rspaces;

5
remnants of damaged alveolar septa.
-

1 1 . Polycystic kidney disease

( R E N POlYCYSTICUS)
H e m atoxyl i n-eo s i n
Polycystic k i d n ey d i sease is a developmental ano m aly with an ad u l t and an i nfanti l e
fo r m . Its pathogenesis i s d u e to the fact that t h e upper a n d lower n e p h ro n fai l to
fuse, resu lt i n g i n cystic d i l atation of the proxi m al nephron by the u ri n e fo rmed i n
t h e glomer u l i . T h e infantile form of t h e d isease is very serio u s and , if extensively
d i ffuse, i ncom pati b l e with l ife. The adult fo rm r u n s a better c l i n ical cou rse and may
become symptom atic o n l y at the age of 50 to 60 years.
Gross Findings. The kid neys m ay attai n an extraordi narily l arge size, sometimes
weigh i n g more than 4,000 gm each in the ad u l t fo r m . Their s u rface i s studded with
i n n u me rabl e f l u id-fi l led cysts which have a m e m b raneous t h i n wal l . Rem n ants of the
ren al parenchyma are p resent o n ly as th i n septa. The cysts vary in size, in advanced
stages of the d i sease they m ay h ave a d i ameter of 1 .0 to 3 . 0 c m .
Microscopic Findings. Large cysts are con s p i c u o u s a m o n g the t h i n col u m n s of p re
served renal parenchyma. I ntact n e p h ro n s may be seen in the u n i nvolved paren
chyma. The cysts contai n homogeneous, fai ntly eos i nop h i l i c fl u id in which occasion
al ly e ryth rocytes m ay be see n . Any part of the n e p h ro n m ay fo rm the cyst wal l . The
cysts m ay be l i n ed by the f l at epithel i u m of Bowman's caps u l e o r by the cuboidal
epithel i u m of the ren al t u b u l es. Where the f l attened epithel i u m of Bowm an 's cap
s u l e fo rms the l i n i ng , occas i o n al ly atrop h i c glomeru l ar loops can be seen p rotrud i n g
i nto the l u men of the cysts. A s the cysts grow, t h e i r epithel i al l i n i ng becomes at
rop h i c and u lt i m ately d i s appears. The b lood s u pply of the i nterve n i ng renal paren
c h y m a grad u al ly d i m i n i s hes and the i n tact n e p h rons al so u ndergo atrophy, t o be
s u bstituted by fibrous co n nective tissue. The i n te rstit i u m is i nfiltrated by chronic
i nf l am m ato ry cel l s , p redom i n antly Iymphocytes .

34

Fig. 1 1 . G

glome r u l u s ; T t u b u l e ; C cystic spaces;

V co mpressed renal parenchyma.
-

1 2 . Testicular atrophy
(ATROPHIA TESTIS)
H e m atoxy l i n-eo s i n
Atrophy of the testes can b e seen i n o l d age, as the en dstage o f orch itis of vario u s
etiologies, i n cryptorch i di s m , a s wel l a s i n e n docri ne ab n o rm al ities, i n mal n utrition,
fol lowing i rradi ati o n o r after treatment with anti neoplastic dru gs . Testicu lar atrophy
is always associated with reduced fert i l ity. I n the study of m al e i nfert i l i ty, beside
cytologic exam i n ation of the ejac u l ate, testic u l ar biopsy is an i mportant sou rce of
informati o n .
Gross Findings. T h e atro p h ic testis is always smal l e r than no rmal . I t s capsu l e, the
t u n ica al b u g i nea, i s g ray to white, somewhat thickened an d wri n k l ed.
Microscopic Findings. The germ cell population in the seminiferous tubules is sig
nificantly reduced in number; spermatogenesis i s m arkedly di m i n i shed. I n m arked
atrophy o n l y a few spermatogo n i a, l arge cel l s with spherical n uclei, and the s u pport
i n g Serto l i cel l s with the base of the i r triangu l ar body on the basement memb rane,
are l i n i n g the sem i n ifero u s t u b u les. D u e to f i b rosis of the t u b u l ar basement mem
brane the wal l of the sem i n ifero u s t u b u les i s thickened, hyal i n ized an d homogene
o u s l y eos i n op h i l ic. The l u men of some t u b u les m ay be completely obl ite rated by
f i b ro u s hyal i n e con nective tissue. The interstitium is markedly increased and i s rich
in co n nective tissue fi bers . Some atrop h i c t u b u l es are s u rro u n ded by rings of co n
n ective tissue fibers (peritubular fibrosis). Concom itant with the i ncrease of connec
tive tissue there is a proliferation of the interstitial Leydig cells. These cel l s form
smal l e r o r l arge r gro u ps in the i nterstiti u m ; the ce l l s have ample, eosinoph i l ic cyto
p l as m and ro u n ded n uclei .

36

Fig. 12. B

thickened, hya l i n ized basal membrane; T

t u b u les ; I

i ntersti t i u m .

1 3 . Anemic infarct of kidney

( I N FA RCTU S ANAEM I C US REN IS)
H e m atoxyl i n-eo s i n
The arter i al s u pply of the k i dneys is p rovided by e n d-arte ries; consequently, i n s uf
ficient arter i al b l oo d flow to the k i dneys can l ead to formation of i n farcts. N u merous
system i c conditions as wel l as specific vascu l ar diseases i nc l u di n g t h ro m boem
b o l i s m , polyarte ritis n odosa, vi sceral Buerger's disease (thrombangitis obl iterans)
and other arte rial diseases can l ead to renal i nfarcts.
Gross Findings. Ren al i nfarcts are con i cal areas which on cut s u rface appear wedge
s h aped, with t h e i r base towards the s u rface of the ki dney and their tip pointing
towards the renal pelvis . The necrotic area i s pale, yel low-white, dry and firm, yet
frag i l e ; the architect u re of the n ecrotic area is i n di st i n ct . The i n farct h as a n arrow
. red r i m of hypere m i a and hemorrhage .
Micrpscopic Findings. I n a typi cal case a triangle-shaped area of necrosis can be
seen i n the ren al pare nchyma. The n ecrotic tissue can eas i ly be distingu ished from
the n o rm al parenchyma becau se it is pale and eosi noph i l ic : o n ly ghosts of glomeru l i
an d t u b u les can b e recogn ized, thei r co nto u rs are obscu red. N o n u clei stai n i n the
n ecrotic tissue. The i nfarcted area i s sharply demarcated from the adj acent u n i n
volved pare nchyma. At its b o u n dary a zone of demarcation is visible where the
m icroscopic structu res are sti l l recogn izab l e and there i s a heavy i n terstitial i nfi ltrate
of polymorphon u cl ear leu kocytes. T h i s m argi n al i nf l am m atory response of polymor
p h o n uclear l e u kocytes is cal led the yellow rim. More towards the u n i nvolved tissues
is the so-cal led red rim which m i c roscopi cal ly s h ows m asses of extravasated erythro
cytes an d m arkedly disten ded cap i l l aries.

Fig. 13A. Top : I

i nfarct; D - zo n e of demarcation ; P - u n i nvolved parenchyma.
Fig. 138. Bottom: T - n ecrotic t u b u les; L - rim of leu kocyt i c i nfi ltrate; G glom eru l u s .
-

38

1 4. H emorrhagic i nfarct of lung

(lN FARCT U S HAEMO R RHAG I CUS PULMO N I S)
H e m atoxyl i n-eo s i n
Hemorrhagic i n farcts of the l u n g develop when an e m bol u s occ l u des a b ranch (or
b ranches) of the p u l mo n ary artery. A p u l mo n ary embol u s will cause an i n farct only
when the p u l mo nary ci rcu l ation i s i m pai red (e. g. i n con gestive heart fai l u re, by a
malignant t u m o r o r othe r c h ro n i c disease) .
Gross Findings. A p u l mo n ary i nfarct is con ical ; on cut s u rface its base poi nts to
wards the p l e u ra and its tip towards the h i l u m . The lesion i s sharply ci rcu mscribed,
s l ightly e l evated above the level of the adjacent parenchyma an d is dark red to pur
p l e an d f i r m , but somewhat frag i l e on palpat i o n . At the tip of the lesion one can
generally f i n d a b ranch of the p u l mo n ary artery occ l u ded by an embolus.
Microscopic Findings. Adjacent to the n o rmal l u n g parenchyma is a necrotic area in
which the architectu re of the l u ng i s i n di sti nct. The n ecrotic tissue shows no n u clear
stai n i n g an d is flooded by e rythrocytes. I n t h i s n ecrotic area the alveol ar septa have
been destroyed and o n l y t h e i r ghosts are recognizab l e . The alveoli are stuffed with
red b l ood cel l s . Towards the edge of the i n farct the n u clei are more percepti ble as
n uclear stai n i ng i nten s i fies i n the bo rder zone. I n the bordering alveoli the desquam
ated p n e u m o n ocytes, as wel l as alveolar m acrophages an d polymorphon uclear
leu kocytes are m i xed with red blood cel l s . An i nf i ltrate of neutrop h i l s is seen at the
edges of the n ecrotic area (demarcation). At the border of the necrotic an d u n i n
volved area t h e alveo l ar septa are widened, t h e cap i l l aries i n them are di lated an d
f i l led with eryth rocytes .

40

Fig. 14. P - l u ng parenchyma; 1- hemo rrhagic i nfarct; 5 - remnants o f alveolar septa;

0 edema fl u i d ; L l u m e n of alveo l u s .
-

1 5 . I schemic i nfarct of brain (encephalomalacia)

( EMOLLlT I O C E R E B R I )
H e m atoxy l i n-eosi n , O i l red 0
C i rc u m scribed l i q uefaction necrosis of the b rai n is due to m arked redu ction o r
cessation of blood f l o w . T h i s m ay be caused by generalized c i rc u l atory i n s ufficiency
(e. g. tem po rary cardi ac arrest) o r fol lowi n g occ l u s io n of the arte rial s u pply by
t h ro m bosi s or an e m bo l u s .
Gross Findings. The foci o f l i q u efacti o n necrosis i n the gray matter are s l ightly dis
colored an d softer t h an the adj acent n o n -n ecrotic tiss u e . I n itial ly the necrotic wh ite
m atte r appears gray an d l ate r yel low as a res u l t of l i p i d droplets acc u m u l ati n g from
the dis i n tegrat i n g mye l i n s heat h s . In l arge r o l d i n farcts a cystic cavity w i l l remain
after di s i ntegration of the n ecrotic brai n tissue.
Microscopic Findings. Cel l u l ar deb ri s an d h omogeneously eosi noph i l ic necrotic
cel l s can be seen at the site of ischemic i nfarctio n . At the rim of the u n i nvolved b rai n
one f i n ds ro u n ded, monon u c lear cel l s which have i ntracytoplas m i c fine vacuoles
from w h i ch the l i p i d was dissolved du r i n g p reparation of the sect i o n . These fat-f i l led
foamy m acrophages (G itterze l l e n o r gitter cel l s) h ave p h agocytized mye l i n debris
which i s then transported i n to the Iymphatics. The l i pi d-laden m acrophages are
p ro m i nent on frozen secti o n s stai ned with O i l red 0, becau se the i r l i pi d-fi l l ed cyto
p l as m is b ri ght red. Bes i de these cel l s there are also phagocytes which contai n
b rown g ran u les of h emosiderin (hemosiderophages) . The u n i nvolved adj acent b rain
i s e de m ato u s ; n o i n flammatory i nf i ltrate ( l e u kocytes, Iymphocytes) are seen i n it. At
a l ater stage there i s a g l i al proliferation ( reactive astrocytosis) aro u n d the i n farct,
fol lowed by an exten sive formation of astrocytic g l i al f i l aments, leaving a firm "gl iotic
scar " .

Fig. 15. Top : Hematoxyli n-eosi n .

E - necrotic area; T - tissue debr i s ; A u n i nvolved bra i n tissue.
Bottom : O i l red O.
Zs - foamy macrophages fil led with l i pi d ; A u n i nvolved brain tissue.
-

42

4)

,.

': .

t
"

,.

'.

.,.

\.

..

... ,

\1

Zs

1 6. Centrilobular necrosis of liver

( N ECROS IS CENTROLO BULA R I S H EPAT IS)
H e m atoxyl i n -eos i n
Vario u s i n j u ri o u s agents o r i nfl uences can p roduce zonal necrosis i n the l iver .
C h aracte ristical ly, zonal n ecrosis diffu sely affects the entire l iver an d sel ectively
damages ce rtai n zones of the hepatic l o b u l e . Correspondi ngly, we di stinguish cen
trilobular, midzonal and peripheral lobular (peri portal) necros i s . Centri l o b u l ar nec
ros is i s caused by chronic passive congestion in severe congestive heart fai l u re, by
drugs (e. g. acetam i n ophen), toxic agents (carbon tetrachloride, c h l o rofo rm, tan n i c
acid) as wel l as hypere mesis gravidaru m .
Microscopic Findings. Changes are seen i n al l lobu les t h roughout the l ive r, and to
the same degree . I n the center of the lobu les, i n the vicin ity of the central vei ns,
there are i rreg u l ar, poorly stai n i ng areas. In these pale, central zones the radial ar
ran gement of l ive r cel l p l ates is l ost; the hepatocytes are pale eosi noph i l ic, have
i n di sti nct ce l l bo rders and their n u clei are s h r u n ke n ( py knotic) or have com pletely
disappeared. These changes are those of coagulation necrosis. In the debris of dam
aged cel l s o n e m ay see erythrocytes and rou n d cel l s (lymphocytes). Occasional l y the
necrotic central area i s s u rro u n ded by a t h i n rim of i nj u red, hydropic hepatocytes
with swo l l e n cyto p l as m . The hepatocytes at the peri phery of the lobu les are i ntact .
The Ku pffer cel l s and e n dothel i al cel l s m ic roscopically appear p reserved.

44

Fig. 16. V

central ve i n ; N

necrotic zone ; H

zone of i n tact he patocytes .

1 7. Simple hyperplasia of endometri um

( HYPE RPLASI A GLA N D U LA R I S CYST I CA E NDOM ETR I I )
H e m atoxyl i n -eo s i n
Endometrial hyperp l as i a i s a pathologic non-i nvasive p ro l i feration of e n dometri u m
i n which t h e e n do m etri u m i s diffusely thickened. I t occu rs as a p ro l i fe rative re
sponse to estroge n i c sti m u l atio n .
Gross Findings. The e n do metri u m m ay b e co n s i derably t h i ckened; i t u s u al ly p re
sents an u n even l y knobby velvety s u rface of soft, red tissue with foci of hemorrhage.
With the u n ai ded eye someti mes small cysts can be observed on its cut su rface .
Microscopic Findings. Stri ki ngly, al l ce l l u l ar components of the e n dometri u m are
hyperplastic. The architectu re differs from that of any phase of the menstrual cycle,
although some m i croscopic feat u res of both proliferative and secretory phase are
p resent. The n ormal l ayers of the e n dometri u m (basal, spongy and compact) are not
recog n izab l e an d the glandular component (gland to stro m a ratio) i s significantly i n
creased. T h e hyperp l astic g l an ds vary i n s ize a n d shape; o n e can see to rtuous,
strai ght and b ranch i n g g l an ds ; some are cystically di l ated with g l an du l ar i nfol di ngs
and outpo u c h i ngs. The l i n i ng of the g l an ds is co l u m n ar epithel i u m , s i m i l ar to that
of secretory p h ase, though the m uc u s p roduction is absent. The g l an du l ar cel l n uclei
are oval an d have u n iform o u t l i n es, l ac k i n g cytologic atypia. The basement mem
b rane of the g l an ds i s recogn izab l e . The stroma i s also hyperplastic, cel l u l ar an d rich
in fine col l agen fibers s i m i l ar to those of prolife rative e n dometri u m . Focal ly the
stro m a i s ede m atou s . The stro m al cel l s are elo ngate, s p i n dl e-shaped; occas i on al
m itoses are n oted. The blood vessels are di l ated, someti mes contai n i n g a t h ro m b u s .

46

Fig. 17. C

cyst ically d i l ated gland ; L l u me n of bra n c h i n g gland ;

H co l u m na r epithel i u m of gla n d ; 5 stroma.
-

1 8 . N odular hyperplasia of prostate

( HYPE RPLAS I A N O DOSA PROSTATAE)
H e m atoxy l i n -eos i n
E n l argement of the p rostate i s a com m o n fi n d i n g i n men over 50 years of age . The
ch anges begi n in the periu reth ral glands. Pres u m ably an i m bal ance in the reg u l ation
of m al e and female (and roge n i c and estrogen ic) hormones plays a ro l e in the
pathogenes i s .
Gross Findings. T h e e n l arged p ro state can be the size of a smal l apple; it e levates
the f u n d u s of the u ri n ary b l adder and n arrows the i nter n al o rifice cif the u reth ra to
a s l it- l i ke ope n i n g . O n cut s u rface m u lt i p l e rou nded yel low to gray nodu les of vary
i n g s izes are seen i n the u nvi nvolved parenchyma which is somewhat firmer and less
succulent.
Microscopic Findings. There i s an i n crease in the g l and u l ar component (adenomat
ous hyperplasia) together with an i n crease i n smooth m u scle and f i b ro u s stroma (fib
romuscular hyperplasia). The g l an d u l ar and f i b ro m u scu l ar components are p resent i n
variab l e p roportions. T h e c l u sters o f closely packed glands con s i st o f cystical ly d i
l ated a s wel l a s n o rm al g l an d s . T h e l u m e n of the g l ands i s l i ned b y a s i ngle l ayer or
pseudostratified cyl i n d rical epithel i u m which h as rou n d central ly positioned n uclei
and pale eos i noph i l i c cytop l as m . This epithel i u m may fo rm small to l arger or branch
i n g short b u d s . The cystical ly d i l ated glands are l i n ed by low cubo idal epithel i u m
(pseudometaplasia). T h e g l an d s do not i nvade t h e stro m a, t h e i r basement mem
b rane i s read i ly recogn izab l e . The l u men of the glan d s contai ns gran u l ar, pale
eos i n o p h i l i c secretion, desqu amated epith e l i al ce l l s with foamy cyto p l as m and l arge
rou nd, concentrical l y l amel l ar struct u res (corpora amylacea), which are ace l l u l ar and
eos i noph i l i c or baso p h i l i c . The con n ective tissue septa between the lobu les are
widened. The i n te rstiti u m contai n s connective tissue fibers and, to vary i n g degrees,
an i n c rease of s p i n d l e-shaped fibroblasts and e l o ngated smooth muscle cells.

48

Fig. 18. 5

sept u m of con nective tissue; L l u m e n of gland ; C cystically d i lated gland ;

A corpus amylace u m ; H
hyperplastic gla n d u lar epithel i u m .
-

1 9. Pul monary edema

( O EDEMA P U L M O N I S)
H e m atoxyl i n-eosi n
C l i n i cally, p u l m o n ary ede m a is a serio u s , l i fe-th reate n i n g condition because the
alveoli of the l u ngs are f i l led with tran s u date which i m pedes gas exchange. Its
pathogenesis m ay be due to increased hydrostatic pressure in the p u l m on ary cap i l
l ary c i rcu l ation and m ay h ave vario u s causes ( left ventric u l ar fai l u re, renal disease,
shock, etc . ) . Dam age of the alveolar capillaries and their i n c reased permeab i l i ty
cau ses p u l mo n ary ede m a i n b acte rial and vi ral p n e u m o n ia. I n h al ation of i rritant,
toxic fu mes or gases (e. g. c h l o r i n e) w i l l also i n c rease the permeab i l ity of alveolar
cap i l l aries and l ead to p u l m o n ary edema.
Gross Findings. Ede m atou s l u ngs are heavy, swo l l e n , pale and feel doughy. The cut
s u rface exudes abu n dant frothy fl u i d.
Microscopic Findings. The alveo l ar spaces are not aerated an d the i nte ralveo l ar
septa appear widened. The di l ated alveoli are f i l led with homogeneou s or finely
gran u l ar, p al e eos i noph i l ic sero u s f l u id. In p rotracted edema the i ntraalveol ar f l u i d
also contai n s des q u am ated p n e u m ocytes. T h e wal l of t h e alveol ar septa i s edemat
o u s an d loose, the cap i l l aries appear com p ressed an d devoi d of b l ood. As a resu lt
of i n c reased cap i l l ary permeab i l ity there are small col lectio n s of extravasated red
b l ood cel l s in the i nterstiti u m .

50

Fig. 19. 5

alveolar septa; 0 edema fl u i d ; C cap i l l a ry;

A desq u amated alveolar pneu mocytes.
-

20. Thrombosis
Mal l o ry's trich ro m e , Wei g e rt's fi bri n sta i n

A thrombus fo rms when blood coag u l ates i n the b l ood vessel s o r i n the heart of
a l iv i n g perso n . The changes in the composition of b lood, i n j u ry of the endothe l ial
l i n i n g of b l ood vessel s , as well as s l ower blood flow o r distu rbance in the lami nar
flow patte rn may p l ay a rol e in the format i o n of a thrombus (th rombosis).
Gross Findings. One can distinguish a white, red and lami nated thrombus. White
thrombi develop when they are superi mposed on a damaged i ntima; they usual ly are
parietal throm b i i n large arteries. These thrombi are tightly attached to the arte rial wal l
and are dry, friable, gray-white with a finely rippled su rface. Red or coagulation
thrombi develop when the blood flow slows down o r stagnates. Red thrombi occur
mai n ly in the vei n s , tightly f i l l i n g thei r l u men. Genera l ly, they are loosely attached to
the wal l of the vei n , are succulent, soft, dark and l ivid. Laminated thrombi occur most
frequently in cardiac and aortic aneurysms. The cut su rface of these thrombi shows
gray-wh ite and dark red streaks ( l i nes of Zah n ) .
Microscopic Findings. Developing (freshly formed) white thrombi consist o f platelets,
leu kocytes and fibri n filaments. The aggregated platelets are faintly eosinophi l ic and
form i rregu larly-shaped, branch i n g trabecu lae which are bordered by a zone of leuko
cytes with dark nuclei. A fine network of fibrin fi laments is recogn izable between these
trabecu lae. O n ly a few scattered red blood cells are seen in white th rombi . The entire
col u m n of blood coagulates in red thrombi; therefore they contain all components of
blood. The fresh red thrombus f i l ls the entire l u men of the blood vessel and consists of
concentrically oriented fine fi laments of fibri n ; between these fibrin filaments one sees
all the cel l u lar elements of blood, but mostly red blood cells. The m icroscopic structure
of thrombi can be conven iently studied with Weigert's fibrin stain which renders fibrin
fi laments violet and conspicuous between yel low-stained eryth rocytes. After a few days
the thrombus begins to break down, its disi ntegrating cel l ular component forms granu
lar debris. From the vessel wal l macrophages enter i nto the debris and dispose of it. The
breakdown of erythrocytes leads to the formation and accu m u lation of hemosiderin in
the organizing blood clot which i s tightly attached to the endothelial l i n ing of the blood
vessel. Proliferating buds of capi l laries and fibroblasts enter the blood clot and a
meshwork of connective tissue fibers develops in the throm bus (organization). Later the
newly formed di lated capi l laries in the th rombus wil l transform i nto larger vessels with
a thicker wal l and endothel ial l i ning. These newly formed blood vessels partly reestablish
the blood flow in the completely occluded segment (recanalization) . With time the sub
stance of the thrombus may hyalinize or calcify.

52

Fig. 20. Top : Mallory's trichrome sta i n ; Bottom : Weigert's fibrin sta i n .
V - wal l of vei n ; Th - th rombu s ; E - eryth rocyte; F - fibrin filaments; 0 - orga n izati o n .

' /.
\
't '

, _....

Th

E
E

2 1 . Fibrinous pericarditis
(PE R I CA RD I T I S FIBR I N OSA)
H e m atoxyl i n-eosi n
F i b r i n o u s exu date m ay be seen on the visceral pericardi u m i n several pathologic
con ditions ( u re m i a, r h e u m atic carditis, auto i m m u ne diseases, myocardial i n farc
tion ) . If the p rocess becomes chron ic, the f i b r i n o rgan i zes and it m ay cause del i cate,
stri n gy adhesions between the visce ral and parietal peri cardi u m or more extensive
i n teradhere nce with com p l ete o b l iteration of the pericardial sac. These m assive
adhesions m ay becom e calcified as if the heart was enclosed with i n a p l aster mold
(concretio cordi s ) , thereby sign ificantly i m pedi n g cardiac fu nctio n .
Gross Findings. T h e pericardi u m appears du l l , it i s covered b y friab l e gray t o tan
exu date , which can be e as i ly w i ped off. If the exu date is vol u m i no u s the fibrin de
posits m at together on the visce ral pericardi u m of the vigoro u sly moving heart an d
give it a ch aracteristic s h aggy appearance resem b l i ng a hairy s u rface (cor v i l l os u m ) ,
also k n own a s " b read an d b u tter" pericarditis.
Microscopic Findings. The myocardi u m an d s u bpericardial fat tissue are u n remark
abl e . The mesothe l i al l i n i n g of the pericardi u m h as been partially destroyed an d is
o n ly focal ly p resent. The pericardial s u rface i s covered by a thick l ayer of
eosi no p h i l ic f i b r i n which focal ly can be recognized as a n etwork of f i n e f i l aments,
e l sewhere it forms c l u mps o r homogeneous m asses. In t h i cker deposits coarse b u n
dles of fibrin are arranged i n l ayers paral lel to the s u rface . U n der the mesothe l i al
l i n i n g there are di l ated and congested cap i l l aries an d ven u les with a scattered inflam
m atory i nf i l t rate of Iymphocytes an d some neutrop h i l ic polymorphonuclear l e u ko
cytes .

54

Fig. 2 1 . P

pericard i u m ; F

fibri n ; C

ven u l e ; I
L

i nflam matory i nfi ltrate;

fat tissue; M
m u scle.
-

p
c

2 2 . Pul monary and cerebral abscess

(ABSCESSUS PULM O N I S ET CE REBRI)
H e m atoxyl i n -eo s i n
Pu ru lent i nf l am m ation can lead to coalescence, that i s , to the development of a
ci rcu mscribed abscess. The most com m o n m icroorgan i s m s i nvolved are
staphylococc i , streptococci and p n e u mococci . M icroorgan i s m s m ay reach the s ite
of abscess fo rmation by di rect trau m atic i nocu l ation or t h rough the b lood stream .
Aspi rat i o n , bronchiectas i a or coalescence of a focus of p n e u m o n i a m ay also lead to
formation of a p u l mo n ary abscess. A b rai n abscess m ay form by di rect i m p l antation
of o rgan isms ( u sually trau m atic) , by exten s i o n of a contiguous p u ru lent i nflamma
tion (e. g. otitis medi a, m astoi ditis) or t h rough hematogenous spread.
Gross Findings. A n abscess is a c i rc u m scribed cavitary lesion which contai n s green
to yellow p u s . The wal l of a recent abscess is del i neated by a grumous, friable mem
b rane; c h ro n i c abscesses h ave a f i r m , fibrous thick wal l .
Microscopic Findings. There i s compl ete destruction o f the u n derlyi n g tissue with
formation of a cavity which contai n s pus cells (polymorp h o n u cl ears an d some mac
rop h ages) , eos i n o ph i l ic cellular debris an d small baso p h i l i c colonies of bacteria. The
cavity is l i ned by a basoph i l ic zone of n ecrosi s , in which eosi noph i l ic f i l aments of
f i b r i n and m any neutrop h i l ic g ran u l ocytes are recogn izab l e . Bes i de these changes,
in the wal l of a c h ro n i c abscess there is a prol iferation of fibrob l asts an d cap i l l aries,
res u l t i n g in the formation of a t h i ck f i b ro u s cap s u l e rich in col l agen fibers . In a brai n
abscess the l i p i ds from the n ecrotic b rai n tissue are p h agocytized by m icrogl i al cel l s
w h i c h become rou n d and h ave foamy cytop l as m after the i r l i pi d content has been
dissolved (so-cal led gitter cel l s) .

56

Fig. 22A . Top : Lung.

A - abscess; G - pus cel l s ; T - l u n g tissue.
Fig. B. Botto m : Brai n .
A - abscess; N - debris o f necrotic tissue; G - p u s cells; Ag - brai n tissue; C ve n u l es.
-

2 3 . Cervicofacial actinomycosis
(ACTINOMYCOSIS CE RVICO FACIALlS)
H em atoxy l i n -eos i n , Pe r i o d i c aci d -Sch i ff react i o n
Act i nomycosis i s a c h ro n i c s u pp u rative disease which occ u rs ch iefly i n its cervico
fac i al , thoracic an d abdo m i n al for m s . Its causative agent is Act i n omyces israe l i i , a
G ram-positive bacteri u m . It i s a com mo n constituent of the n o rm al bacterial flora of
the mouth and can become pathogen i c fol lowi n g local trau m a, operation or i m
m u nosu ppress i o n .
Gross Findings. The re i s a board- l i ke i n du ration i n the region of the mandi b l e o r
neck, respectively. The p rocess u s ually l eads to the fo rmation of a n abscess, which
ch aracteristical ly fl u ct u ates o n p al p ati o n . Later the p u s breaks t h rough to the su rface
of the s k i n or m u cosa by creat i n g a fist u l a. Ch aracte ri stical ly the p u s contai ns grossly
v i s i b l e small ( 1 -2 m m ) yel low gran u l es ( " s u l f u r gran u les"), which are the typical col
o n i e s of Act i n omyce s .
Microscopic Findings. O n e sees an abscess cavity, w i t h i t s wal l an d the s u rro u n di ng
gran u l ation tissue with i nf l am m atio n . The pathogen i n the abscess appears as an
oval to rou n d gran u l e and from its periphery fi l am e ntous struct u res are radiating;
these are eos i noph i l ic an d stai n deep red with the PAS reaction . The gran u les are
e nveloped by p u r u lent exu date an d debris of tissue. The abscess cavity is del i neated
by g ran u l ation tissue wh ich contai ns f i b ro b l asts, ro u n d cel l s and h i stiocytes, the
l atter partly with foamy cyto p l asm ( m acrophages) . On fortu ito u s p l anes of sectio n i ng
the ope n i n g of the fist u l o u s tract can be see n ; it is l i n ed by s q u amous epithel i u m
which i s conti n u o u s with t h e s u rro u n di n g epide r m i s . T h rough the fist u l a colon ies
of bacteria an d p u r u l ent exu date is e m ptyi n g o n the s u rface .

58

Fig. 23. Top : H ematoxyli n-eosi n ; Botto m : Periodic acid Schiff reaction.
actinomyces gran u l e ; 0 debris of tissue and cel l s ; E epiderm i s ; F fistu la;
I
i nflam matory infiltrate; L leu kocytes .
-

24. Mil iary tuberculosis i n lung

(TU BE RCULOSIS MILlARIS PULM O N IS)
H e m atoxyl i n -eo s i n
M i l iary tuberc u losis can deve l o p at any stage of tubercu losis a s a resu l t of
hematogen o u s s p read . If the resi stance of the o rga n i s m i s tem porari l y o r c h ron ica l ly
d i m i n ished, large n u m bers of acid-fast baci l l i may get i nto the bloodstream from
o l der, e ncaps u l ated tubercu l o u s foci and t h u s m i l l et seed size ( m i l i ary) tu bercles
wi l l deve l o p in vari o u s o rgan s .
Gross Findings. T h e l u ngs appear d a r k red t o p u rple, swo l l e n , m oi st a n d heavy.
N u mero u s f i r m , gray-wh ite somewhat transl u cent, very small (1 mm in d iameter)
tubercles can be observed on thei r s u rface u nd e r the p l e u ra or on cut s u rface. Small
tubercles are parti c u larly n u m erou s in the ap ical reg i o n .
Microscopic Findings. The alveol a r arch itectu re o f the l u n g c a n be recogn ized. The
b lood vessels in the septa are congeste d . Scattered in the i ntersti t i u m are rou nded,
c i rcu mscribed gran u lomas which d isplay a characte ristic struct u re . The center of
these gran u lomas i s homoge n o u s , faintly eos i no ph i l ic and ace l l u lar, typical of case
o u s n ecros i s . The n ecrotic center is s u rro u nded by a zone of epithelioid cel l s and
Langhans type giant cel l s . The epith e l i o i d cel l s are elongate, and have a pale sta i n i n g
oval n u c l e u s . T h e Langhans type giant cel l s have a d iameter of 1 50-200 f.L a n d their
smal l , ves i c u l a r n u clei tend to form a wreath at the periphery of the cel l . O utside
the zone of epithe l i oi d cel l s and Langhans type giant cel l s , in the o utermost part of
the tu bercle, there i s a zone of rou nd cel l s , pred o m i nantly Iymphocytes and also
some plasma cel l s .

Fig. 24A. 5 alveolar septa; G - tu bercles.

epithelioid cel l s ; K - rou n d cel l s ; N - necrosis.
-

60

Fig. 24B. L - Langhans type giant cel l s ; E

2 5 . Tuberculous lymphadenitis
( LYMPHADENIT I S T U BE RCULOSA)
H e m atoxy l i n -eos i n
As a r u l e , some lymph n odes are also i n volved i n tubercu losis. Specific lym
phade n i t i s is most often seen in the regional (cervical , b ro n c h i al o r mesenteric)
lymph nodes, depe nding on the l ocation of the p r i m ary i n fecti o n .
Gross Findings. The tubercu l o u s lymph n odes are s i g n ificantly e n l arged an d may
be greater than 1 .0 c m . i n diameter. Their congested cut s u rface reveal s gray to
yel l ow, putty- l i ke areas of variable size. These areas of caseat i n g necros i s may u n
dergo l i q u efaction a n d thei r contents can b reak i nto the l u m e n o f adjacent organs
(e. g. b ronch u s ) , o r can drain through a fistu l o u s tract to the s u rface of the s k i n . The
l atter com mo n l y occ u rs in the cervical region (scroph u lo derma) an d heals with dis
f i g u r i n g scars .
Microscopic Findings. The n o rm al arch itectu re of the lymph n ode can not be recog
n i zed, it is rep l aced by tu bercles of vary i n g sizes and n u m bers. The center of a
typ ical t u bercle h as an eosinoph i l ic center of caseat i n g n ecrosis s u rrou nded by a
zone of epithelioid cells and Langhans-type giant cells. The n uclei of the epithelioid
cel l s are oval , pale stai n i n g and t h e i r body i s e l o ngate. The Langhan s-type g i ant cel l s
h ave a diamete r of 1 50-200 ft , are generally rou n d an d thei r n u mero u s smal l n uclei
are at the periphery of the cel l in a wreath-l i ke arrangement. The tu bercle i s s u r
ro u n ded by Iymphocytes an d p l asma cel l s which represent a tran s itional zone to
ward the cel l popu l ation of the lymph node .

62

Fig. 25A . C - capsule o f lymph node; Ly - lymphoid tissue; N - necros i s ;

E L - epithelioid and Langhan s-type g i a n t ce l l s ; K - rou n d cel l s .
Fig. 258. N - necros i s ; L - Langhans-type giant cells; E - epithelioid cel l s ; K - rou n d cel l s .

Ly

;.:.-

_
_
_
_

26. Mycobacterium tu berculosis

Zieh l-Neelsen

Tuberc u l o s i s i s caused b y Mycobacter i u m tu bercu l o s i s ; th ree m ai n species of

tubercle baci l l i ( h u man, bovi ne, avi an ) are e q u al l y pathoge n i c to man . The h u man
strai n cau ses tubercu losis p r i m arily i n the res p i ratory system , the bov i n e mai n ly i n
t h e al i m e n tary tract, a n d t h e avi an-co mplex typically causes a generalized i nfection
in A I DS patients.
Mycobacte r i a stai n red with the Zie h l - N eelsen stai n , the avi an strai n also gives a
positive PAS-reaction . S i n ce other m icroorgan i s m s m ay also cause lesions h istologi
cal ly s i m i l ar to tubercles, the demonstration of aci d-fast b ac i l l i i s diagnostic. Some
times o n ly after a l o n g search of several specimens can a si ngle or a few aci d-fast
baci l l i be fou n d.
Microscopically, aci d-fast baci l l i are most freq uently fo u n d i n the finely gran u l ar
n ecrotic debris of the caseous center of the t u be rc l e . The baci l l i are scattered or
occ u r in small i rregu l ar gro u p s ; they are 1 -2 long an d 0.4 th i n straight rods,
which stai n red i n a pale b l u e backgro u n d. C h aracteristic aci d-fast baci l l i are some
ti mes e ncou ntered in the cytop l asm of Langhans-type g i ant cel l s .

64

Fig. 26. M

mycobacteria; T

debris o f necrotic ce l l s .

_
_
.-:-

T
____

/M

2 7. Candidal esophagitis
( CA N D I D I ASIS ESOPHAG I )
Pe r i o d i c aci d -Sch i ff react i o n
Can dida al b i cans, a n o rm al i n h abitant o f the mouth, i s the most frequent agent of
fu ngal i nfections in the u pper digestive tract (o ral cavity, esophagus) . Predisposing
factors are long treatment with antib iotics and i m m u nosu p p ression (e. g. acq u i red
i m m u nodeficiency syndrome).
Gross Findings. The lesion o n the m ucosal s u rface appears as a thick, creamy,
pearly wh ite to gray pse u domem b rane wh ich can be wi ped away, leaving a red ooz
i n g s u rface . C l i n ical ly, chron i c can didias i s h as a hyperplastic and an atrophic form .
I n the former, the m u cosa appears thickened, edem ato u s and red; i n the atrophic
fo rm the m ucosa i s e rythematou s , thin and eas i ly rubs off.
Microscopic Findings. The sq u am o u s epithel i u m of the esophagus is u lcerated, the
adj acent stro m a is ede m atou s an d congested. The u lcer is covered by a mass of
f i l amentous structu res (can di da) form i n g a dense tangle of fine th reads which stai n
m agenta with the PAS-reaction .

66

Fig. 27. U

u lcerat i o n ; K

necrotic debri s ; C

filame nts of candida.

28. G ranuloma
(G RAN ULOMA)
H e m atoxy l i n -eo s i n
If fo reign m aterial (e. g. g l ass o r wooden s p l i nters, metal particles, s u rgical s u
t u res, etc . ) gets i nto l iving t i s s u e s o r if deposits of e n dogenous s u bstances which
are i ns o l u b l e i n body f l u i ds (e. g. cho lesterol crystals, u rate crystals, cal c i u m salts)
can not be e l i m i n ated, then they are wal led off by a so-cal led foreign body
gran u loma. L i p i d s u bstances which get i nto the i nterstiti u m by i n j u ry of adipose
tissue ( e . g. b reast) are e l iciting the fo rmation of a so-cal led l i pogran u loma.
Gross Findings. These gran u l o m as are firm, ci rcu m scribed structu res varying from
0.1 to 1 .0 cm . in di ameter. On cut s u rface a fo reign body is someti mes recogn izable.
The center of l i pogran u l om as contai ns yel l ow to tan , poorly c i rcu mscribed fat tissue.
Li pogran u l o m as freq uently are f i rm ly adhe rent to skin scars and can be m i staken for
a tumor.
Microscopic Findings. In the center of the foreign body granuloma there are re
m n ants of s u rgical sutu res cut longitudi n al ly or on cross sectio n . In the i m medi ate
vicin ity of the fo reign body there are i rreg u l arly-sh aped, m u lti n u cleated fo reign
body type g i ant cel l s which have a wide rim of eos i noph i l ic cyto p l as m . These giant
cel l s s u rrou n d the foreign m aterial. In thei r vicin ity there are i nflam m atory cel l s
(Iymphocytes, p l asma cel l s), cap i l l aries a n d p rol iferating yo u n g mesenchymal cel l s
(fibroblasts), t h e l atte r with a n e l ongated cell body a n d oval n u cleus. I f t h e fo reign
body i s not removed, the gran u l o m a wi l l become paucice l l u l ar, f i b rous, wi l l shri n k
and fo rm a scar. T h e lipogranuloma demarcates necrotic fat tissue which, i f l i q u ified,
leaves cavities l i ned by l i p i d- l aden m acro p h ages ( l i pophages, xanthoma cel l s) an d by
the so-cal led To uton-type giant cel l s . The cytoplas m of both cel l types appears foamy
due to the l i p i d which h as been dissolved.

Fig. 28A. Top : S u t u re gran u loma.

M - remnants of su rgical sutu re ;

6'8

0 - foreign body giant cel l ; F - fibroblasts;

K - connective tissue,
Fig. 288. Bottom : L i pogran u l oma.
L - necrotic adipose tissue; T - Touton -type giant cel l s ; X - xanthoma cel l s .

2 9. Peripheral giant cell granuloma

( EP U LIS GIGANTOCE L L U LA R I S)
H e m atoxyl i n-eosi n
T h i s lesion, forme rly called giant cel l e p u l i s, does not rep resent a true neoplasm
but rather is a n exu berant response to i n j u ry of the gi ngiva . Rec u r rance can occu r
after i ncom pl ete s u rgical remova l .
Gross Findings. T h e lesion appears a s a 0 . 5 t o 1 .0 c m . i n diameter, l ivid red, easi ly
b l eedi n g tu mor-l i k e growth of the g u m . The m u cosa coveri n g the lesion i s some
ti mes u lcerated.
Microscopic Findings. N ext to the reg u l ar squamous epithel i u m of the gi ngiva there
i s a cel l u lar a n d vasc u l a r gra n u lation tissue. T h i s is composed of mesenchymal cel l s
with e l ongated n u clei a n d a m o n g them are scattered i rreg u larly-shaped m u ltin uc
leated giant cel l s which resem b l e osteoclasts . The stroma conta i n s small foci of
hemorrhage and macrophages fi l led with b rown coarse gran u les of hemoside rin
(siderophags) . Sometimes remnants of bone trabecu les can be seen res u lting of the
destructio n of parodontal bone.

70

Fig. 29. E

squamous epithel i u m of gu m ; 0

giant c e l l s ; F

fi b roblasts; C

cap i l l aries.

30. Wound healing by fi rst intention

(SA N AT I O P E R P R I MAM I NTENTI O N EM)
H e m atoxyl i n -eo s i n
S u rg ical s k i n i n cisions and non-i nfected cut wou n ds of s k i n heal by fi rst i ntention.
This means that the edges of the wo u n d heal without a sign ificant i nf l am m atory
reacti o n and with the formation of a t h i n l i n ear scar at the site of the wou n d.
Gross Findings. The scar of the wo u n d healed by fi rst i ntention appears l ighter an d
feel s f i rmer than the s u rro u nding s ki n . Scars contain no s k i n appendages (hai rs,
sebaceou s g l an ds) . Recent scars s l i ghtly p rotrude above the s u rface, o l der scars re
tract an d are s l i ghtly s u n ken i n .
Microscopic Findings. The epide r m i s overlyi n g the scar i s o f no rmal thickness as it
h as com pl etely regenerated. S k i n appendages (hair fol l i cles, sebaceo u s gl an ds an d
sweat g l an ds) are absent i n the l i ne of the former i ncision wou n d. No rmal ly, the
col l agen fi bers of the deep ( reti c u l ar) de r m i s are u n ited i nto thick b u n dles which
i nter l ace and are arranged paral l e l to the s u rface of the s k i n . H owever, in the l i n e
of t h e fo rmer i ncision wo u n d t h e col l agen fi bers o f t h e de rmis are thickened and
occas i onally hyal i n ized; here o n l y a few f i b ro b l asts are see n . With the polarizi n g
m icroscope the norm al de r m i s shows a meshwork of b i refringent paral lel arranged
col l agen fibers; in the l i n e of the scar these fi bers are not optical ly ori ented an d
therefore the scar appears as a dark gap . I n the scar no i nflam m atory i nfiltrate is
see n , o n ly a few Iymphocytes. A deve l o p i n g scar h as more cap i l l aries and ven u les,
but with time the n u mber of b lood vessels decreases.

Fig. 30A . Top : E

epiderm i s ; C

l i ne of scar ; A s k i n appendage;
I
i nf l a m m atory i nfiltrate.
normal d e r m i s ; C scar tissue.
-

72

Fig. 308. Bottom (same field with polarized l i ght) :

3 1 . Verruca vulgaris
(VE R R U CA VU LGAR I S)
H e m atoxyl i n -eo s i n
This s k i n lesion i s caused by the h u m an papi l l o m a v i r u s . I t mostly occu rs o n the
f i n gers and the back of the h and of c h i l d re n and you n g ad u lts . The benign lesion
freq uently heals ( d isappears) spo ntaneo u s ly.
Gross Findings. The lesion flatly protrudes above the l evel of the s k i n , has an un
even gray-wh ite to tan-brown s u rface and meas u res 0.2 to 0 . 6 cm i n d i amete r.
Microscopic Findings. The e levated lesion i s covered by a thick hyperpl astic epider
m i s wh ich fo rms pointed p ap i l l ae . The epiderm i s shows i ncreased keratin ization
(hyperke ratosis) res u lt i n g in a s i g n ificant amo u n t of l am e l l ated, someti mes frag
m ented eos i noph i l i c ace l l u l ar kerat i n which covers the papi l l ary s u rface . Th i s hyper
ke ratosi s is o rderly, i . e . no n uc l e i are seen in the kerat i n ( hyperorthokeratosis). The
epiderm al cel l s of the gran u l ar l ayer contai n i n tracytop l as m i c eosinoph i l ic gran u l es,
thei r s h ru n ke n n uclei are d eeply basoph i l i c and are s u rro u nded by an em pty appear
i n g space ( ko i l ocyto s i s) . The vac u o l ated cel l s are referred to as koilocytes. With the
l i ght m i c roscope, someti mes i nc l u s i o n bodies can be seen in the n uclei, suggestive
of a vi ral i n fecti o n . The strat u m mal pi g h i i (the basal , s q u amous and gran u l ar cel l
l ayer o f the epiderm i s) i s i n c reased i n thickness, this ch ange i s referred t o as acan
thos i s . The t h i ckened epidermis extends downward f i n ge r-l i ke e l ongations (cal led
rete ridges) i nto the u pper d e r m i s . The lower ends of these rete ridges tend to point
toward the geometric center of the base of the verruca. The rete ridges are separated
by the papi l l ary derm i s which is u pward ly e l o ngated (pap i l lomatosis) . The basement
membrane i s recognizable and s h arply separates the epid erm i s from the derm i s .
Often there i s a c h ro n i c i nflam m ato ry i nfiltrate i n t h e adjacent derm i s .

Fig. 31A. V verruca; E epider m i s ; D dermis.

hyperke ratosis; G stratum g ra n u los u m ; 5 strat u m spinos u m ;
P rete ridge o f epiderm i s .
Fig. 3 1 C. G stratum gran u l os u m ; K koilocytos i s .
-

Fig. 318. H

74

3 2 . Molluscum contagiosum
H e m atoxyl i n -eo s i n

Mol l u sc u m contagio s u m i s an affecti o n of the s k i n and m ucous memb ranes

caused by a pox v i r u s . I t occu rs in c h i l dren an d you n g i n dividuals m ai n ly on the face
and anoge n ital regi o n . T h i s ben i gn lesion spontaneously i nvol u tes an d heals with i n
a few months.
Gross Findings. The lesion appears as a smal l , 0 . 2 to 0 . 4 cm., dome-shaped pap u l e
above the level of the s ki n . The l e s i o n is waxy, s k i n-colo red an d h as a n u m b i l icated
center from which a small amou n t of gray-white kerat i n debris can be expresssed.
Microscopic Findings. The epide r m i s is extraordi narily t h ickened. The hyperplastic
epithel i u m grows down i nto the de r m i s as m u ltiple, often closely packed lobu l es,
ove ral l fo r m i n g a cu p-shaped lesi o n . The chal i ce- l i ke center of this structu re con
tai n s l arge amo u nts of l am i n ated eos i no p h i l i c kerati n aceo u s mate rial . The basal cel l s
an d t h e strat u m s p i n o s u m do not s h ow stri k i n g abn o rmalities. The cel l s o f the
strat u m gran u l o s u m and strat u m co rneu m are swo l len and contain large (30-35 fl in
diameter) i ntracyto p l as m i c rou n d i n c l u s i o n bodies which become l arger towards the
s u rface of the epiderm i s . The i nc l u s io n bodies swel l up the cel l s and push the n u clei
to the peri phery, n ext to the cel l m e m b rane. The i nc l u s ion bodies are brightly
eos i nop h i l ic an d f i n e ly gran u l ar.

76

Fig. 32. E

i ntact epiderm i s ; K

kerat i n ; I

i nc l u s i o n bod ies; 5 stratum s p i n os u m ;

M basement mem brane.
-

E
E

3 3 . Squamous cel l papilloma of larynx

( pAP I LLOMA LARYN G I S)
H e m atoxyl i n -eos i n
S q u am o u s pap i l l om as are benign neoplastic growths of p roven vi ral etio logy. I n
yo u n g ch i l dren the lesions often are m u lt i p l e (pap i l l o m atos i s ) , the adu lt type i s more
often s i ng l e .
Gross Findings. Pap i l l o m as are exophytic, wart-l i ke growths which are friable, have
a t h i n stal k and meas u re 0 . 1 to 0.5 cm . i n diameter. They are tan-white to red, de
pending o n the t h i ckness of the cove r i n g s q u am o u s epithel i u m . Pap i l l omas occ u r
o n the l aryngeal m ucosa, pri m ari ly a l o n g the true and false vocal cords .
Microscopic Findings. Pap i l l ary fronds are seen which are s u p po rted by f i b rovascu
l ar cores with a tree- l i ke b ranch i n g struct u re . The s u rface of the pap i l lomas i s co
vered by m u lt i l aye red benign s q u am o u s epithel i u m which shows regu l ar stratifica
tion . I n the i r respective l ayers the s q u amous cel l s are oriented, u n iform and stai n
s i m i l arly. The strat u m s p i n o s u m is conspicuou sly wide r (acanthos i s ) . N o rmal mitotic
f i g u res are occas i onally see n . Abnorm al kerat i n ization is not seen among the i m m a
t u re sq u am o u s cel l s . Dependi n g on thei r location, s q u amous papi l lomas m ay focal ly
kerat i n ize; s u ch foci s h ow l am e l l ar caps of eos i n op h i l ic, ace l l u l ar kerat i n . The
epithel i u m is always s h arply separated from the u n derlying con n ective tissue by an
i ntact basement m e m b rane . Foci of lymphocytic i nfi ltrati o n may be seen i n the fib
rovascu l ar cores.

78

Fig. 33. 5

stroma; H

hyperke ratos i s ; A

acanthosi s ; M

basement mem brane.

34. Squamous cell carcinoma of lung

(CA RC I N O MA PLA N O CELLULARE BRO N CH I )
H e m atoxyl i n -eos i n
S q u am o u s cel l carc i n o m as of the l u n gs are freq uent t u m o rs, primarily seen i n
o l de r m e n . The t u m o r orig i n ates from m aj o r b ronchi i n which the m u cosa h as u n der
gone s q u amous metap l as i a fo l l owed by dys p l as i a and carcinoma-i n-situ . C igarette
s m o k i n g is the n u mber one etiologic facto r. The t u m o r is u sually located central ly
an d i s freq uently accompanied by p n e u m o n i a, caused by obstruction of the b ron
c h i al l u men by the t u m o r (obstruction p n e u m o n i a) .
Gross Findings. The t u m o r i s i nt i m ately associated with a b ro n c h u s . I n its early
stage the t u m o r i s a small growth ( l ess than 1 .0 cm) which b u lges i nto the bronchial
l u me n . I n its advanced stage the t u m o r m ay h ave a diameter u p to 1 0 .0 cm or more,
i s poorly c i rcu m scribed and i nfi ltrates the adjacent l u n g parenchyma. Cut s u rface of
the t u m o r is f i r m , g ray-wh ite with scattered yel low foci of necros i s an d dark red
areas of hemorrhage. More extens ive portions of n ecrosis freq uently lead to the
fo rmation of cavities.
Microscopic Findings. S q u amous ce l l carc i n o m as of the l u ng can be wel l , moder
ately o r poorly differen t i ated. Well-differentiated s q u amous cel l carci nomas form
l arger groups an d n ests of cel l s which are arranged in l ayers o r whorl s . The n uclei
of these cel l s are ro u n d, thei r ch romat i n i s loosely distrib uted and stai ns u n evenly.
Occas i o nally mitoses are see n . The t u m o r cel l s h ave ab u n dant, eos i no p h i l i c cyto
p l asm and i n some cel l s den sely eos i no p h i l i c kerat i n aceou s m aterial can be fou n d
(dyskeratosis). Kerat i n pearls typ i cal fo r sq u am o u s ce l l carci noma are n o t frequent.
Moderately differentiated s q u amous cel l carci n o m as do not form cel l nests; the cells
are arranged in i rreg u l ar groups and b u n dles. Kerat i n ization i s rarely see n ; however,
the p resence of i ntercel l u l ar b r i dges (desmosomes) is evidence of a squamous cel l
carc i n o m a. El ectron m icroscopy m ay b e helpful i n i dentify i n g desmosomes. Poorly
differentiated s q u am o u s cel l carc i n o m as are composed of i rreg u l ar, often polygonal
l arge cel l s wh ich h ave lost thei r o ri e ntatio n . The ce l l s have a fai r amo u nt of cyto
p l as m an d p l eomorph ic n u clei . M i toses are fre q uent and often atypical .

80

Fig. 34A. Top : Wel l-diffe rentiated squamous ce l l carcinoma.

K - keratin pearl ; T - nests of tumor cel l s .
Fig. 348. Botto m : Poorly d i fferentiated squamous c e l l carcinoma.
T - tumor cel l s ; M - mitosis.

3 5 . Basal cell carci noma of skin

( BASALlOMA CUTIS)
H e m atoxyl i n -eos i n
Tu mors ari s i n g from the basal cel ls of stratified s q u am o u s epithel i u m were fi rst
descri bed by O d b n Kro m pecher ( 1 902 ) , a H u n garian pathologi st who n amed them
carc i n o m a basocel l u l are . C h aracte ri stical ly, it is a s k i n t u m o r ; it freq uently occu rs
on the face, partic u l arly aro u n d the n ose and u pper l i p , less com mo n ly on the upper
extre m ities and bac k . The tumor i s local ly aggressive and recu rs after i n complete
s u rgical removal . It seldom metastasizes .
Gross Findings. The t u m o r is poorly c i rc u m scribed, flat o r s l i ghtly raised , i n d u rated ,
5 . 0 to 1 5 .0 m m i n d i ameter, o r l arger; it h as an u neven s u rface which freq uently
u lcerates. The tumor grows u n d e r the normal epidermis, cau s i n g its n ecrosi s and
u lceration as if someth i n g was gnaw i n g the s k i n ( u lcus rodens) .
Microscopic Findings. The basal l aye r of the stratified s q u amous epithe l i u m is con
tiguous with cel l gro u ps exte n d i n g i nto the d e r m i s , for m i n g cel l nests which branch
out l i ke f i n gers of a glove. In some cases the t u m o r shows sol i d cel l nests o r smal l
cyst-l i ke struct u res. The outer l ayer o f these cel l nests i s fo rmed by e l ongate basal
cel l s with a pal isade of n uclei . The t u m o r cel l s with i n these n ests are also of the basal
cell type or resem b l e those of the strat u m s p i n os u m . The tumor cel l s stai n d arkly,
d i splay m i ld pleomorp h i s m o r polych rom as i a; m i toses are rare . Adjacent to the
tumor there i s a lymp hocytic i nfi ltrate . The tumor u s u al ly does not extend beyond
the derm i s .

Fig. 35A . E epiderm i s ; T cell nests o f t u m o r ; 5 stroma.

Fig. 358. B basa l type cel l s ; 5 cells of the stratum spinosum type.
-

82

36. Adenocarcinoma of colon

(AD E N O CARCI N O MA CO L I )
H e m atoxyl i n-eosi n
Carci noma of the col o n h as beco me one of the most freq uent malignant tumors
i n m an y i n d u strial ized cou ntries. Precancerous conditions lead i n g to the develop
ment of colon carc i n o m a i nc l u d e v i l lo u s , t u b u lo-vi l l o u s and t u b u l ar adenomas of
col o n , fam i l i al polyposis col i as wel l as ce rtai n cases of c h ro n i c u lcerative col itis.
Gross Findings. The tumor often p resents as a cau l i fl ower- l i ke exophytic growth on
the m ucosa of the l arge bowe l ; its s u rface i s u l ce rated and its edges are i rreg u l arly
heaped u p . On cut s u rface the t u m o r appears f i r m , gray-white. I n its advanced stages
the t u m o r e n c i rcles the l u men which may cause obstructio n (mechanical ileus).
Colon carc i nomas metastasize to the mesoco l ic an d periao rtic lymph nodes and via
the po rtal vei n to the l iver .
Microscopic Findings. T h e adenoma from w h i c h t h e t u m o r arose freq u ently can be
fou n d . I n itially colon carc i n o m as are often polypoid and may i n fi ltrate the lam i n a
p ropria and s u b m u cosa, but do n o t exte nd beyo nd the t u n ica m u scu l aris propria
( D u kes A case) . At a l ater stage the tumor h as grown in cont i n u ity beyond the m us
c u l ar wal l i nto the perico l i c tissues ( D u kes B case) . When the tumor extends through
the serosa o r h as metastasized to lymph nodes it i s a D u kes C case. The tumor forms
i rregu l ar g l an d s which are l i ned by a s i n gle row o r several l ayers of pleomorph ic,
darkly stai n i ng, cyl i nd ri cal epithel i al cel l s . Many m itotic figu res can be observed .
Freq u e ntly the t u m o r cel l s are poorly oriented and are p i l ed upon each other o r
fo rm cel l n ests altogether l ac k i n g a l u me n . Some t u m o rs show no m i croscopic evi
dence of secretory activity , t h e cytop l as m of the i r cel l s stai ns with a basooph i l i c h u e .
I n m any cases, however, the t u m o r cel ls secrete m u cus and may resemble a signet
ring ( "signet r i n g cel l s " ) . Depen d i n g on the amo u nt of secretion such tu mors are
cal l ed m ucu s-secret i n g adenocarc i n o m as (carc i n o m a m uciparu m) or colloid car
c i n o m as (carc i n o m a gel ati nosu m ) .

84

Fig. 36A. M

non- neoplastic glan d s ; T t u m o r with gland-l i ke structu res ; 5

Fig. 368. T tumor cel l s ; M m i tosis; L
-

stroma.
lumen.

3 7. Cystadenocarcinoma of ovary
( CYSTOCARCI N O MA OVARII)
H e m atoxyl i n -eosi n
T h i s t u m o r freq uently arises i n pre-exi stent benign cystadenoma of the ovary by
malignant t ransfo r m at i o n .
Gross Findings. The ovary c a n be enorm o u s , reach i n g a diameter of 1 5 cm o r more .
O n c u t s u rface the t u m o r i s m u lti cystic con s i st i n g of n u mero u s cham bers of varyi n g
s izes and s h apes. These com partments are partly o r al most completely f i l led with
polypoid o r p ap i l l ary cel l growt h s ; sol i d portions m ay also be seen . The cysts are
f i l led with blood-stai ned f l u i d. The wal l s of the cysts are thick , firm an d gray-white
on c u t s u rface. When the t u m o r extends to the periton eal s u rface, it wi l l spread by
i m p l ants an d metastases, cau s i n g sero u s and hemorrhagic ascites .
Microscopic Findings. The t u m o r contai n s cystic spaces which are l i ned by atypical
cyl i n drical epithe l i u m . These t u m o r cel l s can appear i rregu l arly pseudostratified o r
m u lt i l ayered. N u merous m itoses are seen amo n g the darkly stai ned mal i g n ant
epithe l i al cel l s . S i m i l ar epithel i u m covers the pap i l l ary and polypoid growths which
are s u p po rted by bran c h i n g cords of f i b rovascu l ar stroma. The tumor cel l s i nfi ltrate
the stro m a an d also the wal l of the cysts where they form n ests of p ro l i ferating
epithe l i u m an d abortive g l an ds .

86

Fig. 37. C

cyst wal l ; L

l u men o f cysts; 5

stroma o f papill ary growt h ; E b lood vessels;

H carci noma cel l s l i n i n g cyst wal l .
-

H
c

5
E
L

38. I nvasive ductal carcinoma of breast

(CARCI N O MA DU CTAL E MAMMAE)
H e m atoxyl i n -e o s i n
D u ctal carc i n o m a is the most com mon type of b reast cancer. It appears mostly
aro u n d the m en opause, but more recently it h as i n creas i ngly becom e a disease of
you nger women . I ts p rognos i s is favo rab l e in cases in wh ich it i s recogn ized early
and p ro perly treated. I n its more advanced stages the tumor metastasizes mai n ly via
the Iymphatics to the axi l l ary and periclav i c u l ar lymph nodes , sometimes also to the
contral ateral b reast. The tumor m ay di rectly exten d to the chest wal l an d the pleu ra,
an d spreads by the blood stream to the bones.
Gross Findings. I t appears as a firm o r h ard n odu le, most often l ocated i n the u pper
o uter q u adrant of the b reast. It u su al ly is i nfi ltrati n g adj acent tissues and is adherent
to them ; freq uently it i s firmly attached to the overlyi n g ski n , which can become
u l cerated. Cut s u rface s h ows a gray-wh ite nodu l e with spider-leg l i ke extensions
i nto the s u rro u nding tissues.
Microscopic Findings. There i s u sually abu n dant f i b ro u s stroma in which polygonal
t u m o r cel ls rese m b l i n g g l an du l ar epithel i u m are fo r m i n g s m al l e r or l arger cel l nests
an d b u n dles. Sometimes g l an ds with an i rreg u l ar l u men can be seen (adenocar
cinoma fibrosum). I n other types the dense stro m a is more b u l ky and the tu mor cel l s
are scattered si ngly o r i n small gro u ps amon g t h e fibro u s bands o f con n ective tissue
( scirrhous carcinoma o r carcinoma scirrhosum) . Some t u m o rs are extraordi narily
cel l u l ar and fo rm l arge confl uent cel l gro u ps separated only by sparse stroma
( medullary carcinoma o r carcinoma medullare) . Another special form i s the so-cal led
comedo-carcinoma. As the n ame i n dicates, i n this type of carcinoma comedo - l i ke
p l u gs of n ecrotic t u m o r cel l s can be p ressed out on the cut s u rface . Such tumors
contai n i n traductal carci n o m a cel l s an d have a homogeneous, eosi noph i l ic or fai ntly
baso p h i l i c n ecrotic cente r.

88

Fig. 38. T

t u m o r' cel l s ; 5

stroma; N

necrosis.

3 9. Metastatic carcinoma in lymph node

(CA RC I N OMA M ETASTATI CU M LYMPH O G LANDU LAE)
H e m atoxyl i n -eos i n
Mal i g n ant t u m o rs of epithe l i al o r i g i n m etastasize pri m arily by i nvadi n g the reg
i o n al Iymphatics and lymph n odes . The appearance of metastases is always an u n
favo rab l e p rognostic s i g n .
Gross Findings. The l y m p h n odes h arbori n g metastatic carci noma m ay b e signific
antly e n l arged, even up to several centimeters in diameter. On cut s u rface the tumor
appears gray-wh ite an d firm, disti n ctly different from the soft, b rown ish-red
hyperp l astic lymphoid tissue. F r i ab l e coag u l ation necrosi s m ay be seen in the center
of l arge r metastases.
Microscopic Findings. In the e n l arged lymph node the resi du al lymphoid tissue
with hyper p l astic fol l icles can be recogn i zed. In early metastases the tumor cel l s
appear i n t h e s u bcapsu l ar s i n u se s . T h e t u m o r cel l s are con s i derably l arger than Iym
phocytes, h ave more cytop l as m an d stai n l i ghter. In general, the tumor cel l s are
stri k i ngly pleomorphic, the i r n uclei stai n var i ab ly, normal an d ab normal m itoses are
p resent. I n l ater stages gro u p s of t u m o r cel l s i nfi ltrate and rep l ace the lymphoid
tissue and then i nvade the caps u le of the lymph n ode. In advanced stages the tumor
penet rates the caps u l e an d i nfiltrates the adj acent tissues, mostly fat an d m u scle,
without a s h arp bou n dary. H i stologi cal l y metastati c t u m o rs freq uently resemble the
p r i m ary t u m o r ; however, the metastatic tumor m ay al so be less or, seldo m , more
differen t i at i ated t h an the p r i m ary neoplas m . Often i n c l i n ical p racti ce a metastasis i s
fi rst discovered and i t s origi n h as to be estab l ished f r o m the h istologic pict u re .

90

Fig. 39. L - fat t i s s u e ; C - capsule o f lymph node; Ly - lymphoid tissu e ;

T t u m o r nests .
-

40. Tumor cel ls i n pleu ral fluid

H e m atoxy l i n-eosi n

Mal ignant tu mors grow i n g i n body cavities freq u e ntly shed cel l s which can be
fou n d i n the b loody p l e u ral fl u i d, ascites, u ri ne, sputu m , etc. Ben ign and mal i g n ant
cel l s exfo l i ated from the uteri n e cerv i x can be exam i ned in vag i n al smears with the
Papan i co l ao u tech n i q u e . More recently fine n eedle asp i rates from suspicious lesions
of vario u s o rgan s (thyro i d, b reast, lymph nodes, l iver, pancreas, etc . ) are exam i ned
for cyto logic diagnos i s . Cytologic mate rial can be studied on s mears o r on sections
of cel l b locks (after centrifu gation and paraff i n e m beddi ng) . The preparations can
be stai ned with hematoxyl i n -eosi n , G i e msa's or Papan ico l ao u ' s stai n, but can also
be studied with i m m u n o h i stochemical methods o r with the e lectron m i croscope.
A cytologic diagnosis i s often difficult because the exfo l i ated cel l s are eas i ly damaged
before or du ring p reparation of the m i c roscopic specimen . The res u lts of cytologic
exam i n ation always h ave to be corre l ated with the c l i n i cal f i n di n gs an d often a biopsy
is needed to confirm them .
Microscopic Findings. Mal ignant t u m o r cel l s and cel l gro u ps can be seen em bedded
i n fibrin and b loody cel l deb ris. The t u m o r cel l s are of variab l e size and shape
(pleomorphism) and stai n vari ab ly. The n u cleus to cyto p l as m ratio i s i n creased, the
n uclei are l arger an d h ave darkly stai n i n g c h romat i n ( hyperch romasia) . Mitotic fi
gu res m ay be seen, some abnorm al ( e . g . tripolar) m i toses are also p resent. Bes ide
the t u m o r cel l s there are also exfo l i ated mesothe l i al cel l s , polymorphonuclear l e u ko
cytes, Iypmhocytes an d red blood cel l s .

92

Fig. 40. F

fibri n ; T

t u m o r ce l l s ; G

polymorp hon uclear gra n u locytes.

4 1 . Myxoma
H e m atoxyl i n -eo s i n

Myxom as are benign t u m o rs o f m u c i n o u s con nective tissue. The h i stogenesis of

myxomas is u n certai n , s i nce m uc i n o u s co n n ective tissue normally occ u rs o n l y in the
fetu s and in the u m b i l ical cord (Wharton ' s jelly). Myxom as general ly occ u r in the
con nective tissue of the s u bcutis and between m u scle b u n dles as wel l as in the
retro pe ritoneal fat tiss u e . Myxom as are freq u e ntly assoc i ated with other benign
mesenchymal t u m o rs (fib romyxom a, l i pomyxoma, chrondromyxoma) .
Gross Findings. The t u m o r i s generally n ot en caps u l ated, i t meas u res from 1 .0 to
15 cm in diameter, is rou n d or l ob u l ated. Its cut s u rface i s m uc i n o u s , soft, jel ly- l i ke,
gray-wh ite to yel l owish-tan .
Microscopic Findings. Myxomas have few cel l s an d a rich m ucinous gro u n d s u b
stance which appears h omogeneous o r fi nely f i b r i l lar. The gro u n d s u bstance stai ns
pale blue with hematoxy l i n-eosi n , red with m u cicar m i n e and p u rple with tol u idine
blue ( m etac h ro m as i a) s i nce it i s com posed m ai n ly of aci d m ucopo lysaccharides. In
t h i s grou n d s u bstance are scattered ste l l ate o r b i po l ar, s p i n dle-shaped tumor cel l s
w h i c h h ave th i n , e l o ngate a n d b ran c h i n g processes. T h e n uclei o f t h e tumor cel l s
are s m al l , o f s i m i l ar size a n d stai n u n iform ly. N o m itoses are see n . T h e tumor i s
div i ded i nto s m al le r o r l arge r l o b u les b y th i n septa of col l agen fibers. T h e scant
stro m a h as few b l ood vessel s i n contrast to its mal i g n ant form ( myxosarcoma), which
i s q u ite vascu l ar .

94

, Fig. 4 1 . A

g ro u n d su bstance ; T

t u m o r cel l s ,

42. Capillary hemangioma and cavernous hamangioma

( HAEMAN G I OMA CAP I L LARE ET CAVERNOSUM)
H e m atoxy l i n -eos i n
H e m angiomas are benign t u m o rs origi n ating from blood vessels . They occ u r most
freq uently in the s k i n , on the l i ps and in the o ral cavity, less com m o n ly in viscera
( l iver, spleen, b rai n ) an d in bones. Congen ital hemangiomas are thought to arise as
a res u l t of ab n o rm al deve lopment of blood vessel s .
Gross Findings. T h e t u m o rs meas u re from a few m m t o 1 5 c m o r more i n exten sion ;
they are bright red or p u rple, soft lesions which are s l ightly raised. Caverno u s
hemangiomas are soft, h ave a spongy architect u re, and l ivid v e n o u s b lood pours
from thei r cut s u rface .
Microscopic Findings. Capillary hemangiomas are composed of groups of thi n-wal l ed
cap i l l aries divided by t h i n septa of con n ective tissue i nto smal l e r or l arger lobu les.
The t u m o rs are del i neated but not encaps u l ated. The blood vessels are of variable
cal i ber, the i r l u men i s f i l l ed with blood o r eosinoph i l ic seru m . The b lood vessels are
l i ned by a s i n g l e l ayer of f l at or cuboidal e n dot h e l i al cel l s which h ave ro u n d or oval
n u clei . The p ro l i ferat i n g e n dothe l i al cel l s occas i o n al ly n arrow the lumen an d can
fo rm sol i d n ests or i s l an ds of cel l s ( haem angioma cap i l l are hypertrophicu m ) . Caver
nous hemangiomas form l arge, i rregu l ar spaces l i ned by a si ngle layer of flat endothe l i al
cel l s . The wal l s of the vascu l ar spaces are general ly t h i n but can vary i n thickness
an d contai n con n ective tissue fibers, but smooth m u scle cel l s may also be p resent.
The b lood flows very s lowly in the vascu l ar spaces, therefore recent an d organ izi ng
t h ro m b i are freq uently encou nte red in them . In both types of hemangiomas one
may see damage to the wal l of p ro l iferating b lood vesse l s ; con seq uently fresh
hemorrhage as wel l as b rown hemoside r i n gran u les can be observed.

Fig. 42A . Top : Cap i l lary hemangioma.

E - e p i d e r m i s ; L - l u men of blood vessel s ; 5 stroma.
Fig. 42B. Botto m : Cave rno u s hemangioma.
epi derm i s ; C - cavernous t h i n -walled ve i n s ; 5 - stroma.
-

96

43. Uterine leiomyoma

( FIBRO MYOMA UTE R I )
H e m atoxyl i n-eos i n
Ute r i n e l e i o myoma i s o n e of the most freq uent n eoplasms of women . I n general
it carries a good p rognosis and very seldo m u n de rgoes malignant transfo rmatio n .
I n c reased estrogen p roduction o r other hormonal i m balances p resumably play a
role i n the pathogenesis of ute r i n e leiomyom as .
Gross Findings. Leiomyomas of t h e uterus m ay b e subserosal, intramural an d sub
mucosal. They m ay beco m e s u bstantially e n l arged, u p to 10 cm in l argest diameter
and on cut s u rface they are wel l demarcated from the s u rro u n di n g myometri u m .
The t u m o r does not have a caps u l e b u t can eas i l y b e s h e l l ed o u t and removed.
M u lt i p l e leiomyo m as are com mon .
Microscopic Findings. The t u m o r can be di sti nctly separated from the myometri u m .
The myometri u m appears as paral l e l , comp ressed o r anastomosi n g bands o f smooth
m u scl e . The t u m o r shows a vari ab l e p roportion of co n nective tissue fibers an d
smooth m u scle b u n dles which are oriented i n vario u s di rections or fo rm occasional
whorl-l i ke struct u res. The ch aracte ristics of the s mooth m u scle cel l s are best studied
on longitudi n al sections. The n uclei of the smooth m u scle cel l s are elongate, ci gar
s h aped or s p i n dle-shaped and h ave b l u nt or ro u n ded e n ds . The s p i n dle-shaped cel l s
h ave i n distinct bo rders a n d ab u n dant eosi noph i l ic cytoplas m . T h e t u m o r cel l s are
u n iform i n size and stai n s i m i l arly. Mitoses are rare, gian t cel l s or atypical cel l s are
n ot see n . O n cross section the m u scle b u n dles appear to be composed of polygonal
or rou n ded cel l s which h ave s m al l rou n d n u clei . Frequ ently the stroma u n dergoes
hyal i n izatio n ; such areas appear h omogeneous, ace l l u l ar and strongly eosi noph i l ic.
In larger t u m o rs degen erative ch anges may occ u r ; these are smaller pseudocysts o r
foci o f calcification w h i c h are i ntensely basoph i l ic.

Fig. 43A . Low power v i e w : M - myomet ri u m ; T tumor.

Fig. 438. H i gh power view : H - longitudinally cut smooth m u scle fascicle;
K - cross section of smooth m u scle fascicles.
-

98

K
H

44. Rhabdomyosarcoma
H e m atoxyl i n -eos i n , i ro n h e m atoxyl i n

Rhabdomyosarcom a i s a rare, h ighly malignant tumor. Based on c l i n ical and

pathologic ch aracte ristics th ree types can be disti n g u i shed: Pleomorphic rhab
domyosarcoma of adu lts arises i n the skeletal m u scles of the extremities. Embryonal
(botryoid) rhabdomyosarcoma occu rs i n c h i l dren an d you n g adu lts, most often i n
t h e head an d neck reg i o n , part i c u l arly i n t h e orbit . Alveolar rhabdomyosarcomas
are also t u m o rs of c h i l dhood and ado lescence; origi n at i n g i n skeletal m uscle.
Gross Findings. Pleomorphic and alveolar rhabdomyosarcomas h ave a s i m i l ar ap
pearan ce. The t u m o rs vary from 1 .0 to 15 cm i n diameter, l ack a capsule, are soft
and fleshy. Thei r cut s u rface is s h i ny, show i n g a l ob u l ated gray to red mass with foci
of hemorrhage and n ecrosi s . Embryonal rhabdomyosarcomas m ay p resent as a
polypo i d o r botryoi d (G reek word fo r grape-l i ke) growth i n m ucosa- l i ned hol low
organs such as the o ral o r n asal cavities, n asoph arynx, u r i n ary bladder o r vag i n a.
Microscopic Findings. Pleomorphic rhabdomyosarcomas are extraordi n arily cel l u l ar,
amo n g the t u m o r cel l s are the ch aracteristic rhabdomyoblasts scattered or in smal l
gro u ps . A com m o n feat u re of the t u m o r cel l s is the i r b right red, strongly
eos i nop h i l i c cytop l as m s i m i l ar to that of m atu re cross-striated m uscl e . There are also
l arge rou n d or oval rhabdomyo b l ast- l i ke t u m o r cel l s with a wide cytoplas m i c rim and
central n uc l e u s . Other cel l s are l arge, elo n gate, strap-shaped o r ribbon-shaped
which h ave several rou n d n uclei . I n the cytop l as m of these cel l s sometimes i ncom
p l ete cross stri atio n s can be seen which are better demonstrable with special stai n
( i ron hematoxy l i n ) . Anothe r ch aracte ri stic cel l type is ten n i s racket or tadpole
shaped with a vesi c u l ar n uc l e u s i n the b roader e n d ( " head") and a long s l en der
cytop l as m i c p rocess ("tai l " ) . Embryonal rhabdomyosarcomas have a loose, m u c i n o u s
gro u n d s u bstance, whereas i n alveolar rhabdomyosarcomas t h e tumor cel l s are l y i n g
i n alveol i s u rro u n ded b y thick septa of f i b ro u s con nective t i s s u e .

Fig. 44A. Top : H ematoxyl i n -eos i n .

R rhabdomyoblast; E tadpole-shaped cel l ; S
ribbon-l i ke cel l ; D u n d i fferentiated cel l .
Fig. 448. Bottom : I ro n he matoxyl i n . Arrow poi nts to cross-str i ations i n cytoplasm of tumor ce l l .
-

1 00

E
o

R
a

45. Chond rosarcoma

H e m atoxy l i n -eosi n ; Ro m e i s ' sta i n

Chon drosarco ma i s a com m o n p r i mary mal i gnant t u m o r o f the skeleto n . I t affects

mostly o l de r men . The t u m o r may develop in p re-existing benign cartilag i n o u s neo
plasms such as sol itary o r m u lt i p l e enchondromas and osteochondromas .
Gross Findings. The t u m o r may grow to be very l a rge, 20 to 25 cm i n diameter. It
has a lobu l ated appearance, can be cut with a kn ife and may be gelati n o u s ; its cut
s u rface i s transl ucent, white to gray. Areas of n ecrosis, calcificatio n and ossification
may be recog n ized i n it with the naked eye.
Microscopic Findings. C h o n drosarcomas can be wel l-differentiated (Iow-grade) or
dedifferentiated. In well-differentiated chondrosarcomas the gro u n d su bstance
( matrix) resembles that of hya l i n e cart i l age : it is homogeneous, eosi noph i l ic or
s l i ghtly basop h i l ic . The chon drocytes are scattered o r in c l u sters in the cartilage
matrix and are often lyi n g in a lacune s u rro u n ded by a caps u l e . The shape and size
of the t u m o r cel l s va ries, some have hyperchromatic, lobu lated, i rreg u l a r n uclei.
Bi n ucleated o r m u lt i n ucl eated cel l s can be see n , m i toses are freq uent. OccaSional ly,
several t u m o r cel ls l i e in o n e lacu n e . I n some areas the gro u n d s u bstance i s myxoid;
here the cel l s are ste l late and have l o n g p rocesses. Calcificatio n and ossification can
also occ u r . The bone is always fo rmed by osteob lasts i n the matrix (endochon dral
ossificat i o n ) , i n contrast to osteosarcomas where bone develops t h rough di rect
transformation of u n differentiated t u m o r cel l s i nto "tumor" bone. I n less differen
tiated and dedifferentiated chondrosarcomas there is a p ro l i feration of s p i n dle
shaped p r i m itive mesenchymal cel l s which are of variable size and shape. Such
t u m o rs h i sto l ogically resem b l e f i b rosarcomas. In genera l , there i s a goo d correlation
between the m i croscopic appearance (grade of diffe rentiation) and c l i n ical behavior
of chon drosarcomas.

1 02

Fig. 45. Top : Hematoxyl i n -eos i n ; Bottom : Romeis's stai n f o r cartilage.

A ground su bstance; T - tumor cells; P lacuna with tumor cel l .
-

46. Pleomorphic adenoma (mixed tumor) of parotid gland

(ADE N O MA PLEOMO RP H OIDES PAROTlD IS)
H e m atoxyl i n -eos i n
Pleomor p h i c adenoma i s the most com m o n neoplasm of sal ivary g l an ds . Mixed
t u m o rs are s l owly growi ng sol i d neoplasms and occ u r m ai n ly in the parotid glan d of
m i ddle-aged person s . The t u m o r arises less freq u ently in the s u bman di b u l ar gland
an d in the m i n o r sal ivary g l an ds t h roughout the o ral cavity. Larger tu mors may
h ave n u mero u s p rotuberances or f i n ge r-l i ke p rojections which m ay make s u rgical
removal difficult. I n com p l etely removed m ixed tumors m ay rec u r, often as m u ltiple
discrete nodu les n ear the s ite of the p revio u s operat i o n . Sometimes mal ignant trans
formation can be seen after repeated rec u r re n ces.
Gross Findings. The tumor i s encaps u l ated, firm, nodu lar; its cut s u rface i s gray
wh ite to tan with s h i ny, myxo i d o r carti l ag i n o u s areas. Cysts f i l led with m ucoid o r
t h i n f l u i d are occas i o n al ly see n .
Microscopic Findings. There i s a n extrao rdi n ary architectu ral an d cytomorphologic
diversity. The essential feat u re i s that the t u m o r i s com posed of both epith e l i al and
mesen chymal tissues in vari ab l e p roportio n s . The com b i ned occu rrence of different
tissues in m ixed t u m o rs is con s i dered to be due to specific diffe rentiation of p l u ri po
tenti al e m b ryon al epithe l i u m . Pro l i ferat i n g epithelial cells are cuboidal or col u m n ar
s i m i l ar to g l an du l ar epithel i u m or m ay resem b l e myoepithel i u m . The epith e l i al cel l s
form i rreg u l arly-s h aped n ests, trabecu l ae o r cords, someti mes duct- l i ke structu res
f i l led with eos i nop h i l ic secretion . Mucoid connective tissue is also present an d i s
n o t sharply dem arcated f r o m the epithe l i al components. T h e myxoi d amorphous
gro u n d s u bstance stai n s fai ntly an d contai n s e l o ngate o r ste l l ate mesenchymal cel l s .
Other areas s how s m al l e r o r l arge r i s l an ds o f e m b ryon al cart i l age which sometimes
resembles hyal i n e cart i l age ; the size of the cart i l age cel l s an d t h e i r capsu le i s vari
abl e .

1 04

Fig. 46. E

epithelial i s l a n d s ; M E

myoepith e l i u m ; M
P

myxomatous tissue;
cart i l agi nous tissue.

4 7. Wil ms' tumor (neph roblastoma)

( N EPH R O BLASTO MA E M B RYO NALE)
H e m atoxyl i n -eosi n
This mal i gnant t u m o r i s most co m m o n i n you n g c h i l dren ; it is frequ ently as
sociated with autosomal c h ro mosomal abnormalities. Occasionally it can be b i lat
eral.
Gross Findings. The t u m o r appears i n the ki dneys as asol itary, rou n ded soft to firm,
gray-wh ite to red mass enclosed by a pse u docaps u l e . The tumor varies i n size, often
it is large and can be u p to 15 cm i n diameter . It metastasizes most com monly to the
regional lymph nodes, l u ngs and l iver.
Microscopic Findings. The t u m o r typically has a triphasic appearance i ncl uding blas
temal, stromal a n d epithelial cel l types. The blastemal pattern shows closely packed
rou n d cel l s of medi u m size, a ves i c u l a r n u cleus and a t h i n rim of fai ntly stai n i n g
cytoplasm. M itotic f i g u res a r e freq uently see n . T h e stromal pattern may exh i b it s i m
p l e , dense o r loose fibrous con n ective tiss u e . Sometimes t h e cel l u l ar, p leomorphic
and hyperch romatic appearance resembles a f i b rosarco m a ; a m ixtu re of i m mature
s mooth m u scle or cross-striated m u scle e lements may also be see n . The epithelial
patte rn resembles i m mat u re renal t u b u les with a narrow l u men i n sol i d cel l groups.
Occas i o n a l l y the t u m o r cel l s form structu res rem i n i scent of i m matu re glomeru l i .
Wil ms' t u m o rs are u s u a l l y characte rized by the ratio o f thei r various components as
wel l as by the cytologic diffe rentiation and atypia of the components. Prepon derance
of the epithelial pattern carries a relatively favo rab l e p rognosis, particularly if there
is cyst fo rmati o n . The l east favo rab l e o utcom e is seen with the sarcomatoi d form s .

Fig. 47A . B b l astema type cel l s ; T t u b u l a r struct u re ; V blood vesse l .

Fig. 47B. G glomeru l u s - l i ke struct u re ; T t u b u l a r struct u re.
Fig. 47C. F fi brob last-type cel l s ; M m u scle-type cel l s .
-

1 06

48. Malignant melanoma

( M ELAN O MA MALl G N U M )
H e m atoxyl i n -eos i n
M al ignant m e l an o m as are t u m o rs evolvi n g from m e l anocytic p recu rsors. Most
often they arise in the s k i n , but they m ay also o ri g i n ate from the uveal tract of the
eye o r from the lepto m e n i n x . The m aj ority of m e l anomas of the s k i n arises from
n ormal s k i n , o n l y a m i no rity beg i n s in an active j u nctio n al component of a com
pou n d n ev u s . C utaneous m al ignant m e l anomas can be of the s u perficial sp readi ng
o r nodu l ar type. The l atter h as a part i c u l arly poor prognosi s ; it grows an d metas
tasizes rap i dly. The p resence of m e l an i n pigment in the u ri n e (melan i n u ria) is of
diagnostic val u e .
Gross Findings. The dark b rown lesion rises s l i ghtly o r con s i de rab ly above the s k i n
s u rface an d i t s borders are n ot sharply demarcated. I f the melanoma is n o t pig
m ented ( am e l anotic) , the correct di agnosis can someti mes o n ly be made after i m
m u no h i stoche m i cal and/or el ectron m icroscopic exam i n ation (see Appen dix, Case

1 1).

Microscopic Findings. T u m o r cells can b e seen i n al l l ayers o f the ski n . The tumor
i nfiltrates the epiderm i s , overflows the de rmis and exten ds i nto the su bcutaneous
fat tiss u e . Conseq u ently the overlyi n g s k i n u lcerates. The size an d p igment content
of the t u m o r cel l s show great variation ; in some cases the t u m o r cel l s have am ple
cytop l as m (epithe l i o i d cel l type) ; in others they are e l o ngate and form streams (spi n
dle-s haped cel l type) . T h e cyto p l asm contai n s varying amo u nts of brown pigment
( m e l an i n ) . In some cel l s there i s no pigment o r only a few small pigment gran ules;
however, i n the same t u m o r heavily pigmented cel l s with a homogeneously dark
b rown cytop l as m can also be observed. A lymphocytic i nfiltrate s u rro u n ds the
tumor.

epiderm i s ; U
u lcer; T - t u m o r cel l s ; Ly - lymp hocytic i n f i ltrate.
Fig. 488. E epithelioid melanoma cel l s ; M - melan i n pigment.
Fig. 48C. 0 - s p i n d le-shaped melanoma cel l s ; M mela n i n pigment.

Fig. 48A . H

1 08

49. Choriocarcinoma
( CH O R I O N EPIT H ELI OMA)
H e m atoxyl i n -eo s i n
This rare m al i gn ant t u m o r i s composed of trophoblast arranged i n a dimorph ic
p attern and l ac k i n g chorionic vi l l i . I t develops i n the uterus fol lowi n g del ivery o r an
abo rt i o n , l ess fre q ue ntly it is anteceded by m o l ar p regn ancy. Ectopic choriocar
c i n o m as m ay occ u r in the ovary and testi s as a component of a malignant germ cel l
t u m o r o r very rarely as a p u re neoplas m . The t u m o r i s fatal without ade q u ate medical
treatment. Choriocarci n o m as , part i c u l arly those of the uteru s , respond wel l to
cytotoxic chemothe rapy an d can be c u red i n a l arge percentage of cases. Choriocar
c i n o m as p roduce h u m an chorion ic gon adotro p i n (hCG) which is also present in the
u ri n e ; t h u s , a positive p regn ancy test m ay be helpful i n the c l i n ical diagnosis.
Gross Findings. The tumor i s soft, spongy, dark red, s i m i l ar to p l acental tissue.
There are p ale, friab l e , necrotic focuses and hemorrhages o n cut s u rface .
Microscopic Findings. Atyp ical p ro l iferation of trophoblastic cel l s is seen without
stro m a. The t u m o r i nfiltrates the myometri u m an d is com posed of two cel l types,
those of the cytotrophoblast ( Langhans cel l) an d those of the syncytiotrophoblast. The
cytotrophoblastic cel l s are prim itive po lygon al m o n o n u cleate smaller cel l s with pale,
eos i n o p h i l i c , s l ightly gran u l ar cytop l asm an d distinct cel l bo rders. The i r n uclei are
rou n d or oval with f i n e ly dispe rsed c h ro m at i n ; m itotic activity i s evident. The syn
cytiotrophoblastic cel l s are l arge, differentiated, m u lt i n ucleated. I n the i r atypi cal ,
neoplastic form they show n u merous hyperchromatic rou n d n uclei which are i rregu
l arly di stributed in the dense eos i noph i l ic cytop l asm. The tumor is vascu l ar, num erous
di l ated b lood vessels are see n . Some b lood vessels have bee n i nvaded by tumor cel l s
which expl ains t h e p ropensity o f t h e t u m o r f o r early hematogenous metastases.

110

Fig. 49. L - cytotrophoblastic (Langhans) cells; 5 - syncyt i otrophoblastic cel l s .

SYSTEM I C PATHOLOGY

5 0. Fibrosis and fatty infi ltration of myocard ium

( F I BROSIS ET L I PO MATOSIS MYOCARDI I )
Mal l o ry ' s trich ro m e
I n myocardial f i b ro s i s a n i ncreased a m o u nt o f co n n ective tissue diffusely o r foca l ly
replaces the heart m u scle o r i s seen between the m u scle fibers. I n l i pomatos i s of
the myocardi u m there is an abnormal acc u m u lation of adipose tissue with i n the
i n te rstiti u m (fatty i nfi ltrati o n ) . Myocardial f i b rosis can be due to i m pa i red b lood s u p
ply of the myocardi u m , due to certai n i n fectious diseases, or poisons, as wel l as the
res u l t of i n terstitial myocarditis. Fatty i nfi ltration of the heart (myocardial
l i pomatosis) occ u rs most com mo n l y in obesity, but adipose tissue may also rep lace
destroyed m u scle fibers.
Gross Findings. The f i b rotic myocardi u m i s tan , to ugh, not elastic. O n cut su rface
scattered gray-wh ite small patches and th read- l i ke septa can be see n . I n fatty i nfi ltra
tion yel l ow streaks and ban ds exten d from the ove rlyi n g epicardial fat i nto the
myocardi u m .
Microscopic Findings. The myocardi u m i s focal l y rep laced by a n etwork o f con n ec
tive tissue septa . With Mal l o ry's trichrome sta i n the co n n ective tissue fibers appear
deep b l u e and are wel l disti n g u i shable from the red m u scle fibers . The i ncreased
co n n ective tissue separates the myocardial fi bers i nto smaller b u n dles o r, occasion
ally, i nto iso lated segments. At the site of the disappeared myocardial fibers, adipose
tissue may fo rm ; characteristic large spherical fat cel l s are seen which have clear
cytoplas m and a small n uc l e u s . Some resi dual myocardial fi bers encl osed by co n nec
tive tissue have a gra n u l ar sarcoplasm due to damage by hypoxia. Other myofibers
show compen satory hypertrophy; their sarco p lasm i s b u l kier and their n u clei are
l a rge, hyperch romatic, box-car sh aped.

114

Fig. 50. M

myoca rdial m u scle fibers; K

con nective tissue; L

adi pose tissue.

5 1 . Acute myocardial infarct

( I N FA RCTU S ANAEMICUS MYO CA RDI I)
H e m atoxyl i n-eosi n
Myocardial i n farcts are the res u l t of i n s ufficient b lood s u pply to cardiac m u scle.
All p rocesses which cause m arked n arrowi n g o r obstruction of the coron ary arteries
m ay lead to myocardial n ec rosis (e. g. atheroscleros i s, t h rombosis an d other dis
eases of arte ries) .
Gross Findings. The heart appears fl abby, its cut s u rface shows an i rreg u l arly
shaped, geograp h i c map- l i ke, clay-colored, mottled area. This necrotic region is bor
dered by a t h i n , i rregu l ar yel l ow zone which in t u rn is separated from the normal
myocardi u m by a t h i n red zon e . I f the com p l ete cross section of the myocardi u m i s
affected (tran s m u ral myocardial i n farction), there m ay b e fibrin deposition o n the
pericardi u m (fi b r i n o u s pericarditis) and m u ral thrombus formation on the u n derly
i n g e n docardial s u rface .
Microscopic Findings. After 1 2 to 24 h o u rs of i n farction there is recogn izab le dam
age to the myocardi u m . The necrotic myocardi u m can be disti n g u i shed without difi
cu lty from the no rmal heart m u scle . The n ecrotic myocardi u m shows "wavy" fi bers,
the myocytes are struct u ral ly h omogeneous, deeply eos i noph i l ic. The fibrils and
cross stri ations becom e i n di sti nct (and in 2 to 3 days have disappeared) . S i m i l arly the
majo rity of n uclei of the affected myocytes have disappeared; some fibers have swol
l e n o r s h ru n ke n ( py k n otic) n u clei, i n dicati n g necrosis of the fibers. Among the nec
rotic myocardial fi bers the con n ective tissue i s loose, edem ato us, and recent hemor
rhage can also be see n . The necrotic region is demarcated from the n o rmal myocar
di u m by an i nfiltrate of polymorphonuclear neutro p h i l i c l e u kocytes . The grossly vis
ible yel low-red border zone of the i nfarct co rrespon ds to this accu m u l ation of
polymorpho n u clear neutro p h i l s an d e ryth rocytes, respectively. After a few days fine
fat dro p l ets appear i n the sarcop l asm of the n ecrotic myocardial fibers . About seven
days after i nfarction the f i b ro b l asts beg i n to p ro l i ferate an d i nfiltrate the necrotic
area from the adj acent i ntact myocardi u m . G radu al ly new co l l agen i s formed to re
p l ace the n ecrotic myocardi u m .

Fig. 51A. Top : I

i nfarct; M no rmal myocard i u m ; L leu kocytic i nfi ltrate; V eryth rocytes .
Fig. 518. Bottom : P recently necrotic myocard ial f i b e r s ; V extravasated eryth rocytes;
L leu kocytic infiltrate.
-

116

5 2 . Rheumatic myocarditis
(MYOCA RDIT I S R H E U MATI CA)
H e m atoxyl i n -eos i n
Rheu m atic myocarditis i s a m an i festation of acute rheumatic fever, a systemic i l l
ness which i s princi p al l y a disease of c h i l dhood. I n the majo rity of cases there is a
h i story of an u pper ai rway i n fection caused by gro u p A, beta-hemo lytic Streptococ
c u s . Rhe u m atic fever is con s i dered to be an i m m u nologic phenomenon i n which
some anti bodies agai n st streptococcal antigens cross- react with heart antige n s .
Gross Findings. T h e myocardi u m i s p a l e b rown to red, flabby, somewhat brittle.
O n the left s i de of the heart, s u be n docardi al ly an d al ong the smal l b ranches of the
co ron ary arteries, small n odu les appear. These nodu l es are barely visible with the
n aked eye an d are gray-tan , rou n d o r oval o n cut s u rface. In l ater stages of the
disease, when the gran u lo m as h ave healed with fibros i s , they appear as small foci
of gray-wh ite fi rm scar tiss u e .
Microscopic Findings. I n t h e interstiti um o f the myocardi u m , there are ch aracteristic
oval nodules (Aschoff bodies), primarily in the perivascu l ar con nective tissue. The
microscopic appearance of Aschoff bodies changes with progression of the di sease :
we di stinguish an exudative, a prol iferative and a heal ing phase of rheumatic myocar
ditis. I n the early, exudative phase, the interstitial co nnective tissue of the myocardi um
i s loose, edem atou s . Homogeneous eosi noph i l i c foci appear in it; these represent fib
rinoid necrosis. Here the col l agen fi bers are swollen, fragmented and proteinaceous
material precipitates on their su rface . Aro u n d these foci of fibrinoid necrosis there is
an infi ltrate of i nflam m atory cel l s , predomi n antly of neutroph i l ic polymorphonuclear
leu kocytes. I n the proliferative phase the characte ristic m icroscopic picture of an
Aschoff body i s see n , its cyto logic featu res are di agnostic. The center of an Aschoff
body is acel l u lar, eos i noph i l ic and necrotic; it is su rrounded by a zone of rou nd cel ls
(lymphocytes , plasma cel ls) elongate fi broblasts an d large, modified mesenchymal cel l s
(Anitchkov cells). T h e l atter have elongate n uclei with a central band o f chromatin
which on longitudi n al sections resembles a caterpi l l ar. O n cross section the chromatin
bar is s u rrounded by a halo- l i ke space so that the nucleus looks l i ke an owl-eye. The
Anitch kov cell has i rreg u l ar ragged cytoplasm ic borders, sometimes shows
pseudopodia. The origi n of these cel l s i n u n clear, acco rdi ng to some authors these are
modified fibroblasts . Ch aracteristic components of the proliferative phase are the
Aschoff-type giant cells (or Aschoff myocytes) . They have basoph i l i c cytoplasm and
lobu l ated, often mu ltiple n uclei with conspicuous nucleo l i . They also appear to be of
mesenchymal origi n by the i r histochemical an d electron microscopic profi le. In thei r
healing phase the earlier cel l u l ar gran u lomas show fibrosis and hyal i n ization.

118

Fig. 52. A - Aschoff nodule; M

m u scle fibers; N

f i b r i n o i d necrosi s ; An - A n i tchkov ce l l ;
As - Aschoff cel l ; Ly - Iymphocytes.

5 3. Endocardial fibroelastosis
( FI BRO ELASTOSI S E N DOCA RD I AL l S)
Van G i eso n 's e lasti n
Fibroe l astosi s of the endocard i u m is a rare d isease of u n k nown etiology. Thicken
i n g of the e ndocard i u m of the l eft ventricle i m pedes card i ac fu nction early i n l ife .
Gross Findings. The heart i s e n l arged and its cham bers are d i l ated . The m u ral en
docard i u m i s s mooth and d iffusely, o r i n a c i rc u m scri bed area, opal escent pearl
wh ite and feel s rubbe ry. On cut s u rface the e ndocard i u m is conside rably th ickened,
sometimes several m m t h i c k ; it fo rms a rigid l i n i n g of the left ventricle, less com
m o n ly of the left au ricu l ar appendage, right ventricle and l eft au ricu l ar appen d age.
Microscopic Findings. The endocard i u m appears markedly th ickened due to an i n
creased n u mber o f both collagen and elastic fibers. The col l agen fibers are coarse
and appear b l u e with Mal l o ry's trichro m e stai n . E l astic fibers are t h i n ner, wavy and
appear d ark b rown with van G i eson ' s stai n . These con n ective tissue fi bers are ar
ranged in b u n d l es paral l e l to the s u rface of the endocard i u m . There is also an i n
crease of cel l s i n t h e e ndocard i u m : s p i n d l e-sh aped f i b ro b l asts and elongate, ribbon
l i ke s mooth m u scle cel l s are scattered in the thickened l i n i ng. Co l l ections of a few
Iymphocytes are also occas i o n al ly see n . S m al l e r or thicker b u nd les of the co n n ective
tissue fibers are reach i n g i nto the adjacent myocard i u m . S i nce the abnormally thic
kened e ndocard i u m i m pedes an ade q u ate oxygen s u pply of the card i ac m uscle,
small foci of necrosis can be seen in the myocard i u m .

1 20

Fig. 53. M

myocard i u m ; E

endocardi u m ; R

elastic f i bers.

54. Atherosclerosis of aorta

(ATH E ROSCLE ROS I S AO RTAE)
H e m atoxy l i n-eo s i n , O i l red 0
Ath e rosclerosis i s a di sease of the l arge an d medi u m-sized arteries ; i n the cou rse
of the di sease lipids deposit in the i nt i m a and this is associated with increase in
connective tissue (hyalinization) an d calcification of the damaged arte rial wal l . Fac
tors p romoting atheroscleros i s i n c l u de i ncreas i ng age, smoki ng, diabetes, hyper
l i p i de m i a an d hyperte n s i o n .
Gross Findings. There are several types of changes on the i nt i m al s u rface. There are
wh ite hyal i ne f i b ro u s p l aq u es (0.5 to 2 . 0 cm) and yel l ow raised flat streaks or oval
areas (atheromas) due to deposition of l i pids i n the vessel wal l . As the p rocess ad
vances, the overlyi n g i nt i m a m ay become eroded, res u lt i n g i n u lcers with i rreg u l ar
z ig-zagg i n g bo rders. The base of these u l ce rs is covered by a dry gruel-l i ke mass
which contai n s t i n y gl itte r i n g cholesterol crystal s . I n several areas the i ntima may
calcify and resemble an eggshel l . It crackles on p ressu re an d can be readi ly sepa
rated from the vessel wal l . The l u m i n al s u rface of the severely damaged blood vessel
is freq uently covered by fresh , dark red b l ood clots an d o rgan izing, fri ab l e pale red
t h ro m b i .
Microscopic Findings. T h e most severe ch anges are i n t h e intima which i s consider
ably thickened. Among its co n n ective tissue fi bers there are fine droplets of lipid
substances deposited which are b right red with O i l red 0 stai n on frozen sections.
A characteristic feat u re i s the p reci pitation of crystal l i ne cholestero l . I t dissolves i n
alcohol a n d o n sections o f paraff i n -e m bedded tissue o n l y t h e spaces forme rly oc
cupied by the crystals rem ai n . These e m pty spaces are s u rrou n ded by amo rphous
cel l debris an d eos i noph i l ic, p reci pitated p l asma p rotei n s . Large ce l l s with foamy
cytoplas m , which are l i p i d- l aden m acrophages, can also be see n . The accu m u l ation
of l i p i ds i s acco m pan ied by p ro l i fe rati o n of smooth muscle and connective tissue
cel l s, i nc rease of co l l agen fibers which m ay hyal i n ize. The atheromato u s i ntima i s
dem arcated b y a fragmented and frayed lamina elastica interna from t h e media,
which is less damaged. The oxygen s u pply of the blood vessel wal l i s i m pai red by
the l i p i d deposits an d by hyal i n izat i o n , t h u s favo ring dystro p h ic calcificatio n . The
deposits of calci u m salts stai n b l u e with hematoxy l i n an d appear as a cloudy patch
i n the affected area.

1 22

Fig. 54. I

intima; M

media; L

lipids; C

gra n u les of cal cium salt.

5 5 . Cystic madial necrosis of the aorta

(M EDIA N ECROSIS AO RTAE I DIOPATHICA CYSTICA E RDH E I M)
van G i eso n 's e l asti n , to l ui d i n e blue
Also kn own as E rdh e i m ' s disease, t h i s degen erative damage of the aortic media
generally i nvolves the ascending aorta. I t is due to hereditary weake n i ng of vario u s
constituents of t h e con n ective t i s s u e , an d a com m o n featu re i n Marfan 's syndrome.
The wal l of the aorta becomes t h i n n e r an d b u lges . T h rough deh iscences of the i n
t i m a t h e c i rcu l ating b l o o d ente rs t h e aortic wal l an d sp reads i n a plane o f t h e media
to form a dissecti n g ane u rysm . A freq uent an d lethal com p l ication i s rupt u re of the
ao rta.
Gross Findings. The asce n di n g aorta is sign ificantly di l ated and an eu rysmally bu l g
i n g . The aortic wall is paper t h i n and tran s l u cent in some areas.
Microscopic Findings. There are smal l e r o r l arger i r regu l arly-shaped foci of necros is
scattered in the media of the aorta. The e le ments of the medi a, n amely the elastic
fibers, collagen fibers an d smooth muscle cells are eq ually destroyed i rreg u l arly and
at ran do m . I n the u n i nvolved ao rti c wal l the e l astic fi bers stai n dark b rown an d r u n
i n paral lel b u n dles . I n the areas of n ecrosis the e l astic fibers are fragmented, present
in small p i eces and in some wel l-ci rcu mscribed foci they have com p l etely disap
peared. The destroyed media becomes weake r, f l at fiss u res and cystic spaces devel
o p . T h e cystic areas contai n p a l e basop h i l ic m uco i d m aterial ( m ucopo lysaccharides)
which stai ns violet with to l u i di n e b l u e (metac h romas i a) .

1 24

Fig. 55. Top : Van G i eson's elast i n sta i n ; Botto m : Tol u i d i ne b l u e .

I - i n t i m a ; M - media; C - cystic degenerat i o n ; E - remnants o f elastic fibers;
M u - m u coid su bstance.

56. Buerger's d isease

(TH ROMBANGIITIS O BL I T E RANS)
Mal l o ry ' s trich ro m e , Va n G i eso n ' s e l asti n
T h ro m bo an g i i t i s o b l ite rans i s a disease accompanied by t h rombosis and i nflamma
tion of the affected blood vessel s . It occ u rs al most exc l u sively i n yo u n g men ; i nten
sive s m o k i n g i s a p redispo s i n g facto r. The blood vessels of the legs are most com
m o n ly affected, but those of the arms an d viscera m ay also be i n volved.
Gross Findings. A segment of the medi u m-sized and smal l arteries and of the con
com i tant vei n s is occ l u ded by thrombosis an d gran u l ation tissue. In advanced cases
the affected segment becomes a f i r m , cord- l i ke struct u re with total obl iteration of
the l u m e n .
Microscopic Findings. I n t h e early, acute phase o f t h e disease al l l ayers o f t h e wal l
of an affected b l ood vessel are i nf i l trated by polymo rpho n u clear l e u kocytes (panar
teritis) and t h i s i nfiltrate also extends to the adj acent tissues. The i nflam m ation i s
accompan ied b y recent th ro m bosis which occasional l y com p l etely occ l u des the
l u men of the vessel . In the late phase of the disease gran u l ation tissue grows i nto
the l u m e n . This granulation tissue is rich i n cap i l l aries an d fibrob l asts; with golden
b rown hemoside r i n gran u l es i dentified. F i b ro u s con n ective tissue i ncreases in the
vessel wal l , at the s ite of p revio u s i n flammat i o n , as wel l as in the organ izing t h rom
b u s (fibrosis). As the scarred segment of the b lood vessel s h ri n ks, the l am i n a elastica
i nter n a beco m es u n u s u al l y wavy . The n arrow l u me n , the thick vessel wal l and wavy
l am i n a e l astica i nterna t h u s resemble a ruffled span ish co l l ar.

1 26

Fig. 56. Top : Mallory's sta i n ; Bottom : V a n G i eson's elastin sta i n .

l u me n ; Th - organ i z i n g t h ro m b u s ; LE - l a m i n a elastica i nterna; M - media; A adventitia.
-

5 7. Periarteritis nodosa
(PO lYART E RI I T I S N ODOSA)
Aza n , Mal l o ry's trich ro m e
Peri arte ritis ( o r polyarte riitis) nodosa i s a severe disease characterized by necrotiz
i n g i nf l am m ation of the blood vesse l s . The p rocess m ai n ly affects small and medi u m
sized arte ries, and presu m ably i m m u nopatho l ogic mechan i sms are respo nsible for
it. The disease l eads to n ecrosis of the areas s u p p l ied by the affected arte ries i n
vario u s o rgans ( e . g . heart, ki dneys, i ntesti nes) .
Gross Findings. Small f i rm nodules are fou n d on the affected arte ries, primarily at
the site of their bran c h i ng. I n typ ical cases the disease i s segmental , alte rnati ng
wel l-demarcated sections of i nvolved an d n ormal wal l . The damaged arterial wal l is
weakened and con seq u e ntly m ay form an aneurysm o r rupture. Often the l u men is
occ l u ded by a t h ro m b u s .
Microscopic Findings. T h e changes vary acco rdi n g t o t h e phase o f t h e disease. I n
t h e acute phase al l l ayers of t h e arte rial wal l show a dense inflammatory infiltrate of
m o n o n u c l ear ce l l s (lymphocytes, mon ocytes) and neutroph i l ic polymorphon uclear
l e u kocytes. The m edia of the severely affected arte ries shows segmental o r c i rcumfe
rential fibrinoid necrosis which sometimes extends to al l l ayers of the vessel wal l .
The necrotic areas appear homogeneous, strongly eos i noph i l ic and l ack n uclear
stai n i ng. Li ke f i b r i n , the necrotic areas appear b ri ght red with the Azan stai n . The
wal l of the arteries weakened by i nf l am m ation and n ecrosis becomes t h i n ner, may
b u l ge and rupt u re, t h u s vary i n g amo u nts of hemorrhage m ay be seen in its vicin ity.
Acute arteritis is often assoc i ated with thrombosis, which occl udes the l u me n . In a
l ater, proliferative phase of the disease the p ro l i ferat i n g f i b ro b l asts and newly formed
con nective tissue fi bers repai r the n ecrotic port i o n s . The arte rial wal l becomes thic
kened an d defo rmed, the l u men n arrow. The i n flammatory i nfi ltrate is no longer
dom i n ant, although m acrop h ages an d p l asma cel l s are see n . In the healing phase the
arteries appear deformed, have thick, scarred wal l s in which the regu l ar l ayers no
longer can be recogn ized; no i nflammation i s see n .

Fig. 57. Top : Aza n ; Bottom : Mallory's trichrome.

G - renal glomeru l i ; V - renal t u b u l e s ; N necrotic wa l l of artery; T - th rombos i s ;
L i nflam matory i nfiltrate.
-

1 28

58. Kaposi's sarcoma

Azan , H e m atoxyl i n -eo s i n

Kaposi's sarcoma i s a m u lticentric t u m o r of u nce rtai n h i stogenesis; p resumably it

arises from p l u ri potential mesen chymal cel l s . Most often it appears on the s k i n of
the hands o r feet, and it progresses to fo rm t u m o r nodu les i n the vi scera (stomach,
l iver, l u n gs, heart) . General ly, the patients are i m m u n odeficient ( H IV i n fection, post
tran s p l antation, etc . ) .
Gross Findings. Separate, dem arcated, raised, 0 . 2 t o 1 .5 c m i n diameter, red-brown
to p u rple n odu les are seen on the s k i n . The t u m o r nodu l es are soft an d have a
spongy cut s u rface .
Microscopic Findings. An early (granulation tissue like) p h ase and a late (tumorous)
phase can be dist i n g u i s hed. I n the early phase the changes are characte ristic of
gran u l ation tissue; there is a p ro l iferation of t h i n -wal led cap i l l aries which are di l ated
and tightly packed with e ryth rocytes . I n the vicin ity of the e n dothe l i u m- l i n ed vascu
l ar spaces there i s an i n c rease of s p i n dl e cel l s rese m b l i n g pericytes. The interstit i u m
s hows a n inflammatory infiltrate of Iym p h ocytes, p l as m a cel ls, h i stiocytes an d
hemosiderin-Iaden m acrophages . The n ewly-fo rmed blood vessels have th i n wal l s
which are eas i ly i nj u red, the refore extravasated e ryth rocytes and gran u les o f
hemoside r i n are s e e n i n the i n te rstices. I n the late, tumorous phase of Kaposi's sar
coma t u m o r cel l s p ro l ife rate which are con s i dered to be partly e n doth e l i al cel l s an d
partly f i b ro b l asts. I n some t u m o rs n u mero u s blood vessels of variable shape an d
cal i ber are seen an d between them are c l u sters of prolife rat i n g s p i n dl e-shaped cel l s
rem i n i scent o f f i b ro b l asts ( angiomatous type o f t u m o r) . I n t h e other form o f the
t u m o r there are predo m i n antly i m m at u re fibro b l ast- l i k e s p i n dle-shaped cells which
s l i ghtly differ in size and shape. Thei r n uc l e i stai n variably and m itoses can be see n .
T h e t u m o r cel l s form i rreg u l ar b u n dles a n d fascicles between them one sees n arrow
or s l it- l i ke spaces f i l led with eryth rocytes ( fibroblastic type of tumor) . The stroma of
the t u m o r is poor in con nective tissue fibers ; due to recent o r old hemo rrhage
gol de n b rown hemosiderin deposits are fre q ue ntly seen in it.

Fig. 58A. Top : Azan.

E - epiderm i s ; T - t u m o r ; S subcutis.
Fig. 588. Botto m : H ematoxyl i n -eos i n .
T - t u m o r cel l s ; V i nterstitial hemorrhage.
-

1 30

59. Lobar pneumonia

(PN E U MO N IA FI B RIN OSA)
H e m atoxyl i n -eos i n
A wel l recogn izab l e form of i nf l am m ation of the l u ng i s lobar pneumon i a which
i s ch aracte rized by diffuse i nf l am m ation affecti n g the e nti re lobe; i m m u nologic fac
tors also p l ay a rol e i n its pathogenesis. Most often it i s due to Streptococcus
p n e u m o n i ae (pneu mococcus) . It affects m ai n ly you n g an d m i ddle-aged persons who
have a n o rm al i m m u ne syste m .
Gross Findings. O n e o r several l obes of t h e l u n g appear swo l len, e n l arged t o the
size of a l u n g at deep i n h al ati o n . The p l e u ra i s covered by fibrinous o r pu rulent
exu date (concom itant pleu riti s) . The affected lobe i s n ot aerated, its su bstance i s
fi rm l i ke l iver ( hepatization) . T h e n atu ral cou rse of the disease i s 6-8 days, du ring
which its p athol ogy i n vo lves fo u r stage s : con gestion, fo l l owed by red, gray and yel
low hepatization ( h epatisatio ru bra, grisea et f l ava) , depen di n g o n the type of exu
date. In n o n-fatal cases yel l ow hepatization is fol l owed by reso l ution .
Microscopic Findings. The alveolar arch itectu re of the l u ng i s recogn izab l e although
the alve o l i are f i l led with exu date . The i n teralveo l ar septa are widened with di l ated
an d con gested cap i l l aries. The alveol i are f i l led with a network of fibrin f i l aments.
Des q u am ated alveolar l i n i n g cel l s ( p n e u m o n ocytes), eryth rocytes, neutro p h i l i c
polymorp h o n u clear leu kocytes a n d cel l debris are recogn izab l e between t h e fi brin
f i l aments.

1 32

Fig. 59. 5

alveolar septa; L

leu kocyti c exudate; F

fibri n .

60. B ronchopneumonia
H e m atoxyl i n -eo s i n

B ro n chopne u m o n i a is a very com m o n d i sease, seen m a i n l y i n the newborn and

the elderly, but also in i n d ividuals who are i n a poor state of health ( i m m u nocom
p ro m i sed perso n s) . The i nflam mation develops focal ly, scatters t h roughout the l u n g
parenchyma fo l lowi n g b ronchitis o r b ro nc h i o l itis.
Gross Findings. The foci of i nflam mation are restricted to the l u ng parenchyma
com m u n i cati n g with one particular b ro n c h u s (or several b ronch i ) . On cut s u rface
the foci of b ro n chopne u mo n i a appear as s l ightly raised, 0.5 to 1 .0 cm, gray-red to
dark red areas . These areas feel f i rm l y nodu lar, friab l e and o n pressu re small p l ugs
of yel l ow p u s w i l l appear in the m .
Microscopic Findings. Foci o f i nflam mation are seen i n t h e alveoli aro u n d a b ron
chus o r a b ronch i o l e . T h i s i nflam mation i s accompanied by abundant cel l u lar exu
date which con s i sts mai n ly of neutrop h i l ic polymorphon uclear l e u kocytes . Erythro
cytes , f i b r i n and desquamated alveolar l i n i n g cel l s and b ronch iolar epithelial cel l s
are a l so p resent. I f the cau sative m icroorga n i s m i s parti c u la rly viru lent, o r t h e patient
is in a poor state of health, the alveo lar septa u ndergo necrosi s , co l l i q uate and an
abscess cavity forms. A favo rabl e o utcom e i s resol ution with d i sappearance of the
i n t raalveolar exudate and com plete heal i n g . In cases of p rotracted bronchopneumo
nia the exu date may becom e organ ized with col lage n o u s f i b ro u s tissue obl iterating
the alveo l i .

1 34

Fig. 60. B - b ro n c h i o l e ; 1 - l e u kocytic exudate; 5 - i nteralveo lar sept u m .

6 1 . Pneumocystis carin i i pneumonia

H e m atoxyl i n -eos i n , G rocott's
P n e u m ocystis cari n i i p n e u m o n i a i s an i n s id i ou s ly, s l owly deve l o p i n g d i sease ac
com p a n i ed by dyspnea, cyanosis and cough . It is cau sed by Pneumocystis carinii, a
p rotozoan from the class of sporozoites. U s u a l l y it occu rs i n malnou rished, often
p rematurely born i nfants or i n i n d ividuals, whose i m m u n e system is weakened by
congen ital or acq u i red ( H IV) i m m u n od eficiency .
Gross Findings. T h e l u n g pare nchyma shows scattered f i r m , gray-tan t o red patches
rem i n i scent of a glan d u la r patter n .
Microscopic Findings. C h ron ic i nterstitial p n e u m o n i a i s see n . T h e interalveolar
septa are i nfiltrated by Iymphocytes , plasma cel l s and occasional macrophages. I n
some cases eos i n o p h i l i c polymorphon uclear leu kocytes are also p resent. The inter
lobular septa are widened, a n d thei r edemato u s loose con n ective tissue shows a
m o re sparse c h ro n i c i nflam matory i nfi ltrate . The alveoli and alveolar d u cts conta i n
characteristic foamy, eos i noph i l ic mate rial ; someti mes a few macrop hages can also
be observed . The foamy exudate which fi l l s the alveol i shows with the PAS stai n a
h oneyco m b-l i ke pattern i n which the conto u rs of small b u bble- l i ke structu res are
recogn izable. The parasites are v i s i b l e as fai ntly stai ned t i ny dots with i n these b u b
b l e- l i k e structu res and with i n the cytoplasm of the alveo lar macrophages. The cyst
wal l of P n e u mocysti s cari n i i i s wel l demonst rated with Grocott's modified
methenamine silver stai n : the orga n i s m appears as an ovoi d o r co l l apsed , crescent
shaped struct u re, about 4 f,l in d i ameter.

P - plasma cel l s ; E

1 36

Fig. 61A. Top : Hematoxyl i n -eos i n .

eosinoph i l i c leu kocytes; L l u men o f alveol u s .
Fig. 6 1 8 . Bottom : G rocott's methe n a m i n e si lver.
PC - Pneumocystis cari n i i .

6 2 . H yaline membrane disease

( R ESP I RATO RY DISTR ESS SYNDROME)
H e m atoxy l i n-eo s i n
The key feature o f the pathobiology of t h i s d i sease i s the deficiency of p u l monary
s u rfactant p ro d u ced by the type I I p n e u m onocyte s . I n prematu re i n fants p u l monary
s u rfactant is n ot formed or it is i n co m p l ete. Respi ratory d i stress syn d rome is mai n ly
seen i n premat u re i nfants o r i n newborn del ivered by Cesarean section . I n such
babies resp i ration deteriorates a co u p l e h o u rs after b i rth and cyanosis ensues.
Hyal i n e m e m b rane d i sease can also occ u r i n ad u lts, caused by s hock d u e to trauma,
sepsis, burns o r by i n halation of toxi c material.
Gross Findings. The l u n gs are of n ormal size but are heavy. The parenchyma i s
u n u s u a l l y f i r m , p u rp l e to red , with occasional hemo rrhagic foc i .
Microscopic Findings. T h e l u ngs a re atelectatic, b u t some aerated, conspicuously
d i l ated alve o l i and alveol a r d u cts are also see n . The alveo lar l i n i ng cel l s appear i ntact
however, i n some areas they are desq uamated d u e to anoxia. The wal l of the d i s
tended, aerated alveoli i s l i ned by a h omogeneous eosi noph i l ic thick hyaline mem
brane which can also be seen along the wal l of the alveo lar d ucts . The hya l i n e mem
b rane sta i n s for l i pi d , and gives the Feulgen reacti o n fo r DNA as wel l as the PAS
reaction . The l u me n of the alveoli is fi l l ed with f i n e ly gran u lar-appearing eos i no p h i l i c
e d e m a f l u i d . Focal and more exten sive i n traparenchymal hemo rrhage i s seen d u e to
hypoxem i c damage of the cap i l lary wal l s .

Fig. 62. T - non - aerated (atelectatic) l u ng parenchyma; A alveolar l u m e n ;

H hyal i n e membrane.
-

1 38

63. Pulmonary sil icosis

(SILICOSIS PULM O N I S)
Azan
S i l icosis i s a p n e u moco n iosis caused by the i n halation of s i l i con d ioxide ( s i l ica)
contai n i ng d u st. The s i l i ca grad ually d i s solves from the i n haled particles and causes
necrosis of the alveol a r macrophages . The released fibrob last sti m u lati ng factor pro
d u ces focal progressive f i b rosis which leads to fu rther com p l i cati o n s .
Gross Findings. I n the early stage o f the process the l u ng parenchyma conta i n s
finely c repitant sand- l i ke material and scattered s m a l l fi rm nod u les . I n a later phase
of the d isease i ncreas i ngly larger s i l icotic nod u les form which can become coales
cent and are v i s i b l e with the n a ked eye . These s i l i cotic n od u l es are u n usually f i r m ,
someti mes rock-hard and between them thick co rds of dense fibro u s t i s s u e a r e ex
tend i ng to the t h i ckened f i b ro u s pleu ra.
Microscopic Findings. In the early phase of the d isease an i ncreased n u m ber of
p hagocytes are fo u n d i n the alveol i and b ronchioles. The s i l ico n d ioxide contai n i n g
d u st sti m u lates t h e alveolar macrophages t o phagocytose t h e i n haled particles. The
i n corporated particles acc u m u late in the p hagolysosomes and damage their mem
b rane which then wi l l r u ptu re . Conseq u ently the affected cel l s die and d i S i ntegrate.
T h u s the tox i c agent, s i l i con d ioxide, aga i n reaches the i n terce l l u lar space in which
it slowly d i ssolves and i n d uces an extraord i narily i ntensive p rod uction of con nective
tissue in the late phase of the d i sease. The c l u sters of d u st-contai n i ng macrophages
occasionally fo rm small gran u lomas which are s u rrou nded by Iymphocytes and
plasma cel l s . As the d i sease p rogresses, these gra n u lomas become cel l -depleted
( hypocel l u lar) and wi l l u ltimately transform i nto ace l l u lar fibrous nod u les. These
con si st of concentric whorled b u n d l e s of eosi noph i l ic homogeneous, hya l i n ized col
lagen fi bers. The silicotic nodules may show central necrosi s . With polarized l i ght
b i refringe n t need l e-s haped s m a l l crystals of s i l i cate particles can be demon strated
i n s i l icotic nodu les. T h i s is an i m portant feat u re i n the d i fferential d iagnos i s of s i l ico
tic nodules. S i l icosis i s often associated with anth racos i s ; in such i n stances carbon
deposits can also be seen as b lack pigment part icles in the cytoplasm of the mac
rophages and i n te rstiti u m of the l u ng.

1 40

Fig. 63. P

d u st particles; G

gra n u loma; 5

i n teralveolar septa.

G
5

64. B ronchogenic small cell carcinoma

( CARCINOMA M I CROCE L L U LARE BRO N CH I )
H e m atoxy l i n-eo s i n
S m a l l ( "oat " ) cel l carci noma i s a com m o n p r i mary l u n g t u m o r . The majo rity of
'
pati ents are men and heavy s m o kers of cigarettes. The rapidly growing tumor is
h ighly mal ignant and p ro n e to give early metastases. Some small cel l carci nomas are
hormone-p rod u c i n g and can cause vari o u s e ndocri ne syndromes.
Gross Findings. The tumor forms a peri h i l a r mass (located near the p u l monary
h i l u s ) ; generally it origi nates in the m a i n bronchus or one of the maj o r bronch i . The
t u m o r m ay grow to become 10 to 15 cm in d iameter, although it someti mes is less
vol u m i n o u s . The t u m o r is poorly c i rcu mscri bed and i nfiltrates the i ps i l ateral h i lar
structu res and l u n g parenchyma . I ts cut s u rface i s gray-wh ite, soft, friable, d ry and
mottled with foci of n ecrosis and hemorrhage.
Microscopic Findings. The markedly cel l u lar t u m o r fo rms nests and fascicles of i r
reg u l a r shape a n d s ize, which are divided by t h i n septa of con nective tissue. Seldom
the tumor cel l s s h ow a ci rc u l a r arrangement and pseudorosettes. The tumor cells
are smal l , mostly elongate and resem b l e grai n s of oats (hence its other name, "oat
cel l carci noma" ) . The cel l n uc l e i are oval or s p i n d l e-shaped and have basoph i l ic,
finely gra n u lar, sti ppled ( " salt and pepper"-l i ke) n uclear ch romati n . The n uclei are
s u rro u nded by a th i n r i m of cytoplasm with an i n d i stinct cel l border. The cytoplasm
contai n s some argentaff i n gra n u les wh ich occas i o n a l ly can be demonstrated with
s i lver methods. The s hape, size and ti nctorial q u al ities of the cel l s are somewhat
variable; n u m e ro u s normal and abnormal m itoses are seen . Rarely small cel l car
c i nomas contai n c l u sters of large cel l s with abu n dant cytoplasm suggestive of
squamous cel l d i fferentiatio n .
Electron microscopic examination o f t h e cytop lasm o f the tumor cel l s reveals varying
n u m bers of m e m b ra ne-bo u n d , dense-core gran u les which are s i m ilar to the
n e u roendocri n e gran u l es seen in the Ku ltsch itzky (argentaff i n ) cel l s . The capabi l i ty
of small cel l carc i n omas to p rod uce hormones and the p resence of neu rosecretory
gran u les i n the t u m o r cel l s suggest that the small cel l carci nomas arise from cel l s of
the so-cal l ed APU D system p resent i n the a i rways.

Fig. 64A . Top : P b ronchial ca rti l age; T - t u m o r ; M - b ronchial m u cou s glands.

Fig. 648. Botto m : Z - small ( " oat"-) cell carci noma; 5 septum of connective tissue.
-

1 42

65. B ronch ioloalveolar carcinoma

(CA RC I N O MA BRO N CH I OLOALVEOLARE PULMO NIS)
H e m atoxy l i n -eos i n
B ronch i o l oalveolar carci noma i s a rare l u n g tu mor. It i s n ot clear whether the
t u m o r a ri ses from the alveo lar p n e u m o nocytes or from the epithel i u m of the termi
nal b ro n c h i o l e s . Most of the t u m o rs are peri p heral and therefore asymptomatic u nt i l
late i n the co u rse of the d i sease. A l t h o u g h b ronchioloalveo lar carcinomas a r e wel l
d i ffe rentiated and seldom metastasize, a late d i agnosis carries a l ess favo rable prog
nosis.
Gross Findings. The t u m o r may be a sol itary mass, but more often it p resents as a
d i ff u se lesion a n d , s i m i lar to p n e u m o n i a , it may i nvolve an entire lobe of the l u n g .
O n cut s u rface t h e t u m o r appears f i r m , gray t o wh ite a n d opaq uely s h i ny , ooz i ng
m uc i n o u s secretio n .
Microscopic Findings. T h e growth patte rn of bronc h i o loalveolar carci noma resem
bles the n o rmal architectu re of the l u ng, because the t u m o r cel l s p ro l i fe rate along
the p reserved con n ective tissue of the alveolar wal l s . The tumor cel l s are col u mnar
o r cuboidal a n d have basal n uclei . Their cytoplasm i s eosi n o p h i l ic, with varying
amou nts of m uc i n o u s vacuoles. T h i s s uggests that the tumor arises from the m u cu s
secret i n g cells of the te r m i n al b ronch ioles. The t u m o r cel ls u s u a l ly fo rm a s i ngle row
and are regu larly a l i g n ed along the con nective tissue of the alveolar septa. Some
ti mes pap i l l a ry sta l ks p roject i nto the l u m e n , thei r b ranch i n g core i s covered by the
above described t u m o r cel l s . In some areas the tal l col u m nar t u m o r cel l s are shed
i nto the alveolar space s . Less well d i fferentiated areas resemble pneu m o n i a : the
alveol i are com pletely f i l led with t u m o r cel l s of vary i n g shapes and sizes.

1 44

Fig. 65. T

l u ng parenchyma; 5

alveolar septa; L

l u me n ; 0

tumor cel l s .

66. Sinus histiocytosis of lymph node

(SI N US CATA R R H US LYMPH O G LANDU LAE)
H e m atoxyl i n -eo s i n
S i n u s h i stiocytosis is often seen i n lymph n odes d rai n i ng i nflam mato ry lesions o r
carci nomas. The changes develop i n response to chronic sti m u lation b y regional
i nfect i o n , toxi c agents, m echan ical o r physical i n j u ry.
Gross Findings. The lymph node i s en larged, ru bbery , and has a pale gray to red
cut s u rface. Protracted c h ro n i c i nflam mation of a lymph n ode may lead to depletion
of the lym phoid cel l popu l ation with i n c rease of con nective tissue, s h ri n kage and
scarring.
Microscopic Findings. The e n larged lymph node appears cel l u l ar, its arch itecture i s
recogn izabl e . S i g n i fi cantly d i lated s i n u ses f i l led w i t h h istiocytes a r e compressi n g the
lym phoid tissue. On l o n gitud i nal sections these s i n u ses are cu rved or branch i n g
and stan d o u t because o f thei r p a l e sta i n i ng . The l u men o f the d i l ated s i n u ses i s
l i ned b y e ndothel ial cel l s . T h e y a r e partia l ly o r com p l etely f i l led w i t h h istiocytes
( macrophages) . These m ed i u m-sized cel l s have oval or bean-shaped n uclei and mod
e rately abu ndant cytoplas m . Scattered among the s i n u s h i stiocytes are also small
Iymphocytes .

1 46

Fig. 66. C

caps u l e of lymph node; Ly - lymphoid tiss u e ; 5

s i n uses.

67. Leukemic i nfiltrate in the liver

( I N FILTRATIO L E U KAEM I CA H EPATIS)
H e m atoxyl i n -eo s i n
A characte ristic of l e u ke m i as i s the prolife ration of neoplastic white blood cel l
precu rsors which i nf i l trate vari o u s o rgans a n d tissues. I nfi ltrates o f l e u ke m i c cel l s
are most com mo n ly seen i n t h e b o n e marrow, lymph n odes, spleen a n d l iver.
Gross Findings. In c h ro n i c l e u ke m i as the l iver i s considerably en larged ; it i s tan and
its free margi n s are ro u nded. Petechial hemorrhages are seen u n der G l i sson's cap
s u l e ; on cut s u rface the parenchyma is frag i l e . I n c h ro n i c myelogenous l e u ke m i a the
l o b u l a r architectu re of the l iver is p ro m i nent. I n c h ro n i c lymphocytic l e u kemia the
cut s u rface shows s m a l l (0.1 cm) gray foci of tumor.
Microscopic Findings. Leu ke m i c i nfiltrates d i ffer from solid tumor deposits si nce
they a re not wel l demarcated and the h istol ogic architect u re of the i n fi ltrated tissue
can be recogn ized . I n itially the l e u ke m i c cel l s aggregate in the vicin ity of b lood
vessel s , then grad ua l ly i nfiltrate the i n terstiti u m of the i nvolved o rgan, compressing
the pare nchyma and cau s i n g its atrophy. In chronic myelogenous leukemia the hepatic
lobu les are diffusely, u n ifo r m ly i nfiltrated by abnormal myel oge n o u s prec u rsor cel l s .
These are seen m a i n ly a l o n g t h e s i n u ses convergi n g o n t h e central vei n , between
the trabec u l ae of the l iver. I n this i nfiltrate myeloge n o u s tumor cel l s at vario u s levels
of d i ffe rentiation can be seen ; myeloblasts with large n u clei showing a loose
c h romat i n pattern and a t h i n rim of cytoplas m ; myelocytes, with smaller, ova l ,
eccentric n uc l e i , and a broad r i m o f cytoplasm w i t h azu ro p h i l i c o r neutrop h i l ic cyto
plasmic gran u le s ; metamyelocytes, with smaller, bean-shaped n uclei and matu re
polymorpho n uclear neutrophilic granulocytes. The atypica l , i m matu re myeloid cel l s
can also b e seen scattered i n t h e periportal a n d peri b i l i a ry con n ective tissue. The
l iver trabec u l ae are com p ressed and th i n ; the hepatocytes are atrop h ic, their cyto
p lasm contai n s small vac u o l es and b rown pigment gra n u les. I n chronic lymphocytic
leukemia the i n f i ltrates form circumscribed foci i n the l iver, m a i n ly i n the peri portal
con n ective tiss u e . The cel l s of the i nfi ltrates consi st of abnormal Iymphocytes with
rou nd , hyperc h romatic n uclei and a th i n cytop lasm ic ri m .

Fig. 67. Top and Bottom, left : M L i nfiltrate o f chronic myeloge nous leukemia;
V central ve i n ; M trabeculae of h epatocytes .
Bottom, right : LL
i nfiltrate of c h ro n i c lymp hocyt i c leukemia.
-

1 48

68. H odgkin's disease

( LYMPH O G RA N U LOMATOSIS, M O RBUS H ODG KIN)
H e m atoxyl i n -eos i n
Hodgki n' s d i sease i s a neoplasia of lymphoid tissue and i s separated from non
Hodgki n 's lym phomas by its c l i n i cal and pathological feat u re s . In the early phase
Hodgki n 's d i sease affects the cervical lymph n odes, later it p rogresses to i nvolve
othe r regions and becomes general ized , its i nfi ltrates cau s i n g e n largement of the
spleen and l iver.
Gross Findings. The lymph n odes are e n larged, up to 2.5 cm i n d iameter. In the
early stage the lymph n odes are d i st i n ctly separate; with progressi o n of the d isease
they become less wel l d efi n ed a n d get b o u n d together by t h i ck fibro u s bands. The
cut s u rface of recently d eveloped lesions is gray-wh ite and soft; advanced, old le
s i o n s are f i r m , resi l ient, f i b ro u s .
Microscopic Findings. T h e n o rmal architect u re of t h e lym p h n o d e i s effaced b y a n
i nfi ltrate o f a m ixed cel l popu lation i n w h i c h Iymphocytes, eosinophilic leukocytes,
plasma cells a n d neoplastic histiocytes are see n . D iagnostic are, however, the Reed
Sternberg cells. These giant cel l s have a m p l e cytoplasm and a characteristic b i lobate
(or someti mes m u lt i l o bate) n ucleus which appear pale and have l a rge n ucleol i . S i m i
lar large cel l s w i t h o n e oval p a l e n ucleus c a n a l s o be see n ; these monon uclear vari
ants are the Hodgkin's (or lacunar) cel l s . The m icroscopic pict u re may be com
pou nded by foci of n ecrosis and vary i n g amou nts of fibrosis. Based o n its m icroscop
i cal appearance Hodgk i n 's d i sease can be classified i nto vari o u s types. The most
favo rabl e category i s the one with lymphocytic predominance, in which the Iympho
cytes are d o m i nant in the i nf i l t rate . I n the mixed cellularity gro u p n eoplastic h i stioc
ytes and Reed-Ste r n berg cel l s are m o re n u m erou s and a l l of the characteristic cel l u
lar components a re p resent, often accompanied by foci of n ecrosi s and fibrosis. This
category i s less favo rabl e . The least favorab l e gro u p i s the Iymphocyte depletion form
in which the Iymphocytes have almost com pletely d isappeared and pleomorph ic
sarcomato u s appear i n g Reed-Ste rn berg cel l s are seen in the f i b ro u s stroma. A spec
ial form of H odgki n ' s d i s ease is the nodular sclerosis type in which thick b u n d l es of
con nective tissue form islands d i v i d i n g the arch itectu re of the lymph node.
In these i s lands o n e of the above mentioned h i stologic type can be d o m i nant.

1 50

Figs. 68A and 8. S R - Reed-Sternberg giant cel l ; H o - Hodgki n 's (or lacunar) cel l s ;
H i - neoplastic h i sti ocyte; L y - Iymphocyte ; K - f i b r o u s stroma ( i n m i xed c e l l u l a rity type) .
Fig. 68C. S - septa of con n ective tissue; T nodu les of tumor ( i n nodu lar sclerosis type).
-

69. Non-Hodgkin's lymphoma

H e m atoxyl i n -eosi n

Malignant n eoplasms of lymphoid tissue which cl i n i cally and m icroscopically are

othe r than Hodgkin's d i sease, are cal led non-Hod gk i n ' s lymphomas. N u m e rous
types of such t u m o rs are known , from rel atively favo rable ones with a good p rog
rwsis to h ighly mal i gnant, lethal form s . A s lowly p rogressive, moderately mal ignant
lymphoma is the centroblast-centrocyte type which origi nates from the B-ce l l s of the
ger m i nal center of lymphoid fol l icles. A h ighly mal ignant type is the immunoblastic
lymphoma, wh ich may develop i n i m m u n odeficient i nd i v i d u al s and i s often as
sociated with i m m u nosuppressive therapy o r auto i m m u ne d i seases.
Gross Findings. The i nvolved lymph nodes are markedly e n larged and may have a
d iameter of several cm . The lymph nodes are soft and on cut s u rface the i r s u bstance
i s b u l g i n g and fish flesh-li ke, pale p i n k to white.
Microscopic Findings. In the centroblast-centrocyte type lymphoma the p ro l iferat i n g
t u m o r cel l s fo rm d i st i n ct , wel l-demarcated fo l l icles (nodular form). Later t h e pro
l iferati n g cel l s grad u a l l y i nfi ltrate the adjacent tissue (nodular-diffuse form) and u lti
mately the n od u lar pattern co m p l etely d isappears (diffuse form). The newly formed
n eoplastic fol l i cles are oval o r rou nd and s i m i lar in size. They are com posed of smal l
a n d l a rge lymphoid t u m o r cel l s which rese m b l e the cel l s of the normal germ i nal
center of lymphoid fol l icles. The small cel l s (centrocytes) are s i m i l a r in size to n o rmal
Iymphocytes ; the i r n uc l e u s sta i n s darkly, i s i rregu larly rou n d and u s u a l ly has a cleft
l i ke i nd entat i o n . The large cel l s (centroblasts) are 1 0 to 30 i n diameter ; thei r n uc
l e u s i s rou nd , a n d has loosely arranged pale stai n i ng c h romati n . I m m u no h i stochem
i cal stu d i es reveal that the cel l s of the newly fo rmed neop lastic fol l icles are mono
clonal a n d ca rry the kappa o r gamma l i ght chains of i m m u noglobu l i n (see also Ap
pendix, Case I Va) . I n contrast, the adjacent n o n - n eoplastic lym p ho i d tissue consists
of a n o rmal polyclonal lymp hocyte popu lation .
I n the immunoblast type lymphoma the infiltrate shows characteristic tumor cel l s .
T h e n u cleus o f t h e immunoblasts i s large, oval with a loose c h romat i n pattern and
a thick, basoph i l i c n u clear m e m b rane; the n u cleol u s i s u sually prom i nent. Mitoses
are freq uent. The cel l s have a s u b stantial cytoplas m i c rim in which strongly PAS-posi
tive material c a n be see n , correspo n d i n g t o i m m u n oglob u l i n . I f t h e t u m o r becomes
d i fferentiated, plasmablasts and occasi o n a l ly matu re plasmace l l s can be see n . Plas
mablasts a re smal l e r than i m m u n ob lasts and have a n eccentric n ucleus with a
cartwheel-l i ke c h romat i n pattern . I n the i r cytoplasm i m m u noglobu l i ns can be de
monstrated with i m m u no h i stochem i cal tech n i q u e s .

1 52

Fig. 69A. Cb - centroblasts; C c - centrocytes .

Fig. 69B. I b - i m m u nob lasts ; PB pl asmablasts.
-

70. Multiple myeloma

( MYELOMA M ULTIPLEX)
H e m atoxyl i n -eos i n
T h i s t u m o r i s of p l asma cel l origi n and secretes m o noclonal i m m u noglob u l i n . I t
most often occ u rs i n i n d ivid u al s over 5 0 years of age . T h e abnormal i m m u noglobu l i n
can b e demonstrated i n the seru m a n d u ri n e , the l atter i s referred to a s Bence j ones
prote i n . The t u m o r has a poor p rognosis, despite treatment there i s an 80% five-year
m o rtal i ty rate.
Gross Findings. N u merous ro u n d , soft, gray to red t u m o r nodu les can be fou n d i n
bones (calvari u m , jawbo nes, vertebra, ribs a n d l o n g bones of t h e extrem ities) .
Microscopic Findings. Pro l iferat i n g plasma cel l s are seen i n a sparse network of
con nective tiss u e . The t u m o r cel l s a re i n var i o u s stages of matu ration and are fairly
pleomorp h i c . The n uc l e u s appears normal and has an eccentric positio n ; its hetero
ch romatin i s darkly stai n i ng and i s occas i o n a l l y arranged l i ke the spokes of a wheel .
Cel l s with two o r even th ree n u clei can be see n . The b road cytoplasm i c rim i s
basoph i l ic and the m id d l e of the cytoplas m i s occ u pied by a p a l e area (the Golgi
apparatus) adjacent to the n uc l e u s . The t u m o r cel l s can be d i fferentiated from reac
tive plasma cel l s with i m m u no h i stochem ical tech n iq ues which demonstrate monoc
lonal l ight chain i m m u nogl o b u l i n i n the cytoplasm of neoplastic p lasma cel l s .

1 54

Fig. 70. P b - plasmablasts ; P s - plasma cel l s ; L

fat vacuole.

7 1 . Cytomegaloviral infection of parotid gland

(CYTOM EGALlA)
H e m atoxyl i n -eo s i n
Cytomegalov i ral (CMV) i nfection u sed to be a rare d i sease, occu rri n g mostly i n
newborn v i a vertical (transplacental) tran s m i ss io n . I n some i n stances i t has been the
cause of p rematu re b i rth an d/or malformat i o n s . More recently CMV i nfection has
been seen in i m m u n od eficiency (e.g. A I DS patients) o r as a con sequence of i m
m u nosu ppressive therapy i n ad u l t patients .
Gross Findings. T h e parotid glands may b e s l ightly swo l l e n .
Microscopic Findings. T h e evidence o f i n fection i s most l i kely t o b e seen i n the
smaller d u cts of sal ivary gland s . The epith e l i al cel l s of some d ucts appear normal, i n
others they are s i g n i ficantly swo l l e n , u p t o tenfold o f t h e n ormal d iamete r. The
cytoplasm of the swo l l e n cel l s conta i n s tiny basop h i l i c gran u les. The n ucleus is also
markedly swo l l e n and conta i n s a large ro u n d , strongly eos i noph i l ic i nc l u sion body
s u rro u nded by an optica l l y clear, halo-l i ke space, rem i n i scent of an owl's eye. Some
of the damaged cel l s get detached from the basement membrane and get i nto the
secreti o n of the paroti d gland . The demonstration of these cells in the sal iva i s d i ag
n ostic. I n the peri d u ctal con n ective tissue there is a lymp hocytic i nfi ltrate of varying
i ntensity.

1 56

Fig. 71. A

aci n i of parotid gla n d ;

small i n t raparotid d u cts; Z

i nclusion bod ies.

72 . Chronic sialadenitis
(SIALOADENIT I S CH RO NICA)
H e m atoxyl i n -eo s i n
I n flam mation o f the maj o r sal ivary glands i s freq u ently of bacterial origi n . The
most i m portant pred i spos i n g factor is d i m i n i s hed secretion of sal i va which can be
d u e to d ehyd ratio n , med ication , rad iation or tra u m a . An i m portant eti ologic factor
i s stagnation of sal iva d u e to obstruction by sialolithiasis. I n n eglected cases the
i n fection penetrates the caps u l e of the gland and i n vo lves adjacent tissues .
Gross Findings. The i n vo lved sal ivary gland is swo l l e n , f i r m , sensitive to touch and
its secretion of sal iva i s d i m i n ished. Pu r u l e nt exu date may e m pty from the main d u ct
on gentle massage of the gland. O n cut s u rface gray, fi rm tissue can be seen with
o bs c u re l o b u l a r struct u re .
Microscopic Findings. T h e destruction of aci n i i s n oted and with i n t h e i nvolved
l o b u l e they are replaced by fibrous tiss u e . Some resi d u a l aci n i are l i ned by cubo i dal
epithe l i u m . A lymphocytic and plasma cel l u lar i nfi ltrate of variable i ntensity i s seen
in the i n te rstiti u m . The d u cts are d i lated and there is a peri d u ctal rou n d cel l i nfi ltrate.
The con nective tissue of the i nterlobular se pta is also i ncreased and may be foca l ly
homogeneo u s , eos i noph i l i c d u e to hyal i n e degeneratio n .

1 58

Fig. 72. A

aci n i ; D

d ucts ; L

lymphocytic i n f i ltrate.

73. Radicular cyst

( CYSTA RADICULAR IS)
H e m atoxyl i n-eo s i n
This most com mo n odontoge n i c cyst occu rs at the apex of a tooth and i s a res ult
of bacterial i nfection of the pulp chamber and root canal as a consequence of dental
caries. The cyst develops as a seq uela of a periapical gra n u loma, its epithelial l i n i n g
i s de rived from the epithel ial rests o f Malassez w h i c h p ro l i ferate i n response t o the
i nflam mato ry sti m u l u s .
Gross Findings. A thi n-wal l ed cyst, 0.5 to 1 .0 c m . i n largest d iameter, i s seen at
tached to the apex of the extracted tooth . I f the cyst is to rn off d u ri n g extract i o n , it
has to be removed from the alveo l u s becau s e the residual epith e l i u m wi l l give rise
to f u rther growth ( residual cyst) .
Microscopic Findings. The cyst i s l i n ed by stratified kerat i n iz i n g squamous
epithel i u m which seldom prod u ces s u b stantial amou nts of kerat i n . The epithelial
l i n i n g may be absent at sites of i ntensive i n flam mation i n the cyst wal l . In the
epithel i u m n u mero u s hyaline bodies (Ru shton bod ies) m ay occu r. These tiny, l i near
or a rc-shaped bodies are strongly eos i noph i l i c , b rittle, and occas ionally fragmented .
The cyst wal l con s i sts of parallel b u n d l es of col l agen fibers, with fibroblasts and
small b lood vessels among them . As a conseq u ence of i n fection an i nfi ltrate of ro u nd
cel l s (Iymp hocytes, plasma cel l s) i s seen n ear the epithel i u m . I n the wal l of the cyst
someti mes there are s l it- l i ke spaces ( left by d i s so lved cholestero l crystals) which are
s u rrou nded by m u ltin u cleate d , foreign body type giant cel l s . With i n the l u men of
the cyst there may be pale , eosi noph i l i c p rote i naceou s p recipitate (fl u id ) .

Fig. 73. E - epithelial l i n i n g ; K con nective tissue; L - l u men o f cyst;

Ch - spaces left by d i ssolved cho lesterol crystals; H
hyal i n e bod ies.
-

1 60

74. Benign Iymphoepithelial lesion

(LA ES I O LYM P H O E P ITH ELlALlS)
H e m atoxyl i n -eo s i n
The benign Iymp hoep ithel ial lesion is the man ifestation of an i m m u nologically
med i ated process (M i k u l icz's d i sease) in which the sal ivary gland tissue p resumably
plays a rol e . There i s u n i lateral o r b i l ateral swe l l i ng of the parotid gland, which i s
acco m pa n i ed by xerosto m i a . T h e p rocess m a y be l i m ited t o one sal ivary g l a n d or
may be a component of Sjogren's synd rome.
Gross Findings. The sal ivary gland i s con s iderably en larged , fi rm and on its cut
s u rface the characte ristic l o b u l ated glan d u lar architect u re i s barely recogn izab le.
The cut s u rface i s tan to red , resem b l i n g that of lymph nodes.
Microscopic Findings. There i s sign ificant damage to the glan d u lar parenchyma.
The destructio n of aci n i appears to start in the area of i ntral obular d u cts . An i ntensive
lym p h ocytic i nfiltrate is seen aro u n d the d u cts and grad u a l l y rep laces the d i sappear
i n g gland u lar pare nchyma. Scattered fo l l ic u l a r centers may also be seen in the d if
fuse lymphocytic i nfi ltrate . The l u men of the destroyed d u cts is obstructed and i n
some areas the i r epithelial cel l s prol ife rate t o form groups (epi myoepithe l ial i slands) .
These conta i n a syncyt i u m of both d u ctal epithelial and myoepithel ial cel l s . I n older
e p i myoepithelial islands there are i nterce l l u lar deposits of an eosi noph i l ic hyal i n e
s u bstance w h i c h i s excessive basement membrane materia l .

1 62

Fig. 74. A - aci n i ; Ly - lymphoid i n filtrate; E - epi myoepithelial i s lands.

75. Oral leukoplakia

(LE U KOPLAKIA M U COSA E O R I S)
H e m atoxyl i n -eos i n
Le u koplakia i s a c l i n ical term descri b i n g a wh ite patch (plaque) on the m u cosa of
the mouth o r othe r site covered by stratified squamous epithe l i u m . T h i s wh ite patch
can not be wiped off a n d is pai n less. It occu rs pri marily in m i d d le-aged or elderly
perso ns a n d i s associated with heavy cigarette smoki ng. Other etio l ogic facto rs are
excessive alcohol co n s u m pt i o n , poor o ral hygiene, l ocal physical and chem ical
c h ro n i c i rritants . Leu koplakia is a precancero u s con d ition which may u n dergo mal ig
nant transfo rmation i n 5 to 6% of the cases.
Gross Findings. There i s a ci rc u m scribed, i rregu larly-shaped wh ite patch most com
m o n l y on the m ucosa of the tongue, the cheeks o r the g u m . The s u rface of the
lesion may be sm ooth (simple leukoplakia) o r i rregu larly-elevated (verrucous
leukoplakia), someti mes mottled with fiss u res and e rosions (erosive leukoplakia).
Malignant transformation can not be recognized c l i n ically and can be d i agnosed o n ly
h i stol ogical ly.
Microscopic Findings. A thick laye r of homogeneous eosi noph i l i c lamel lar keratin
can be seen (hyperorthokeratosis). Sometimes pyknotic n uclei are also present in
the kerat i n layers (hyperparakeratosis). The squamous epithe l i u m i s stri k i ngly
hyperplastic with a p ro m i nent strat u m gran u lo s u m and p ro l iferation of cel l s with
wide n i n g of the stratu m s p i n o s u m (acanthosis). The ridges of the epiderm is may be
elongated and extend i nto the con n ective tissue of the l a m i n a propria. The basement
m e m b ra n e i s i n tact. I n the u nderlying con n ective tissue foci of chro n i c i nflam mation
may be see n . If mal ignant transfo rmation occ u rs, the reg u l a r stratification of the
epithe l i u m d i sappears, the darke r basal type cel l s p ro l i ferate, mitotic activity i n
creases , t h e cel l s become pleomorphic and there i s abno rmal and p rematu re
kerat i n ization of i n d ividual keratinocytes (dyskeratosis).

1 64

Fig. 75. K

kerati n ; G

strat u m g ra n u losu m ; 5

stratum spinos u m ; B basal layer;

Ly - lymphocytic i nfi ltrate.
-

Ly

- .
,

..

' V..'

\ .

"

..

...
:

.
.... .

.. ,

...."

Ly

76. G ranular cell tumor

H e m atoxyl i n -eos i n

The origi n o f t h i s t u m o r has n ot been com p l etely clari fied , because the normal
co u nterparts of the characteristic gran u lar cel l s have not been identified as yet.
These t u m o r cel l s were thought to be of myoblast origi n , but recent i m m u nohis
tochem ical stu d i es s uggest a n e u roge n i c t u m o r . S i n ce m o rphologica l ly s i m i lar
gran u l a r cel l s can occu r i n othe r t u m o rs as wel l (e.g. i n ameloblastomas) , it i s as
s u med that the gra n u lar cells develop as a res u lt of a degenerative p rocess. The
t u m o r can occ u r anywhere in the oral cavity o r at othe r sites, but it i s most common
in the ton g u e .
Gross Findings. T h e t u m o r appears a s a 0.5 t o 1 .5 c m . firm, asymptomatic mass ; it
can be m i staken for a f i b ro m a . The overlying m ucosa i s i n tact. O n cut s u rface the
gray to white lesion stands out in contrast to the m u scle of the to ngue.
Microscopic Findings. The t u m o r cel l s fo rm i rregu l a r b u n d l es, nests o r gro u ps
which extend without sharp del i n eati o n i nto the adjacent m u scle fi bers . The gran u lar
cel l s are po lygonal o r ro u n d , the i r abu ndant cyto plasm i s pale and conta i n s charac
teristic s m a l l eos i noph i l ic gran u le s . The n uclei of the gra n u lar cel l s are sma l l ,
rou nded and d a r k stai n i ng . T h e cel l s are not pleomorphic, m i toses are very rare. The
overlying stratified squamous epithel i u m can be u n u s u a l ly hyperplastic and may ex
tend i rreg u l a r elongate p rojections i nto the tu mor. This growth pattern is cal led
pseudoepithel i o mato u s hyperp las i a which can be m istaken fo r squamous cell car
cinoma.

1 66

Fig. 76. M

fi bers o f striated m u scle; T

t u m o r cel l s .

77. Ameloblastoma
H e m atoxyl i n -eos i n

Amelobl asto ma i s the most freq uent odontoge n i c t u m o r . I n general i t occu rs i n

ad u lts, most com mo n ly i n the 4th to 5th decade o f l ife. The t u m o r i s most often seen
in the molar regio n of the man d i b l e . Although h isto logical ly benign, the tumor is
loca l ly aggressive and has an i nf i l trative growth patter n . The t u m o r wi l l recu r if i n
com p l etely exci sed . Fran k malignant transfo rmation i s also poss i b l e .
Gross Findings. The affected jawbone shows marked expansion which o n
roentgenograph s appears as a u n i locular o r m u lti locular cystic lesi o n . T h e t u m o r i s
n o t e ncapsu lated , i nfi ltrates the adjacent b o n e and the s u rro u n d i n g cortical b o n e i s
t h i n ne d . The gray-to-wh i te t u m o r m a y conta i n cysts of vary i n g sizes.
Microscopic Findings. Nests of p ro l iferat i n g epithe l i u m are seen in a scant stroma.
The t u m o r cel l s resem b l e amelobl asts of the enamel organ . The most common type
is the follicular ameloblastoma i n which the arrangement of the tumor cel l s resem
bles that of n o rmal dental fo l l icles. The col u m n a r cel l s pal i sading at the periphery
of the cel l nests are ameloblast- l i ke whereas centra l ly they fo rm a loose, reticu lar
epithe l i u m . Ameloblastomas can have several othe r s u btypes. O n e of these shows
cystic d egen e ratio n i n the center of the epith e l i al islands (cystic ameloblastoma).
There are also ameloblastomas i n which the tumor cel l s fo rm anastomosing cords
(plexiform ameloblastoma) or may show kerat i n ization (acanthomatous ameloblas
toma). I n some t u m o rs the central cel l s may have a finely g ra n u lar eosi noph i l ic
cytoplas m (granular cell ameloblastoma). There is no n oteworthy correlation be
tween the cl i n ical cou rse and the var i o u s h i stologic s u btypes of amelob lastoma.

1 68

Fig. 77. Top : Fol l i c u l a r amelob lastoma.

ameloblast-like t u m o r cel l s ; R reticu la r epithel i u m ; C - m i c rocysts.
Fig. 77. Bottom : G ra n u lar cell ameloblastoma.
A ameloblast-l i k e tumor c e l l s ; G - gra n u l a r cel l s ; C mic rocysts.
-

78. Warthin's tumor

( CYSTADEN OMA PAPILLAR E LYM P H O MATOSUM)
H e m atoxyl i n -eo s i n
Warth i n ' s t u m o r occu rs i n m id d l e-aged o r e lderly perso ns. Most freq uently i t pre
sents in the paroti d gland, more seldom i ntraoral ly. I ts s u pportive tissue resembles
a regu lar lymph node; the t u m o r i s the conseq uence of a developmental anomaly.
Pres u mably d u ri n g e m b ryonal development rests of sal ivary gland epithe l i u m are
left beh i n d i n i ntraparoti d lymph nodes and decades later the tumor arises in them.
Wart h i n 's tumor may be bi lateral and rarely it may be m u lticentric.
Gross Findings. In a typical case a fi rm o r fl u ctuant mass can be fou n d in the lower
pole of the parotid glan d . The t u m o r i s encap s u l ated , its cut s u rface i s tan to brown
with small cysts and clefts of variable size from which sero u s or m u coid brown f l u i d
o r pasty d e b r i s c a n be expressed .
Microscopic Findings. I rreg u larly-s haped cystic spaces of vario u s sizes are seen and
b ranch i n g papi l l ary structu res protrude i nto the i r l u me n . The tumor i s em bedded in
reg u l a r lym phoid tissue in which fol l icles and s i n uses can be recogn ized . The cysts
and pap i l lary growths are covered by b i l ayered col u m nar epithel i u m which i s
b ri ghtly eos i noph i l i c and shows no atypia. The s u perficial layer i s com posed of tal l
col u m n a r epith e l i u m , its oval n uclei are u n i formly oriented a n d are n ear the d i stal
pole of the cel l s . A basement membrane separates the epithel ial l i n i ng from the
lym phoid stroma.

1 70

Fig. 78. P

papi l l a ry growt h ; Ly - l y m p h o i d tissue; B - basal layer of epithel i u m ;

S s u perfi cial layer o f col u mnar epithe l i u m .
-

79. Adenoid cystic carcinoma

(CA RCI N OMA ADE N O I DES CYST I C U M )
H e m atoxyl i n -eos i n
Adenoid cystic carci noma i s a m a l i gnant t u m o r bel i eved to arise from the i nterca
lated d ucts of sal i vary glands. The t u m o r most fre q uently origi nates i n the m i n o r
sal ivary glan d s ; t h u s it i s seen o n the palate, b u ccal m u cosa o r i n n e r s u rface o f the
l i p s . Among the maj o r sal ivary glands it is most often fou n d in the parot i d .
Gross Findings. The tumor most often p resents as a fi rm i ntraoral mass, sensitive
to pal patio n ; the ove rly i n g m ucosa is u l ce rated early. The tumor freq uently spreads
peri n e u ral ly, cau s i n g pai n , sensory changes and paralys i s .
Microscopic Findings. U n d e r l o w power t h e tumor shows a lace- l i ke patte r n . The
t u m o r cel l s are smal l , cuboida l ; thei r n uclei are hyperch romatic and relatively large.
Cel l u lar atyp ia i s not a stri k i n g feat u re , m itoses are rare. I n the center of the cel l
nests there a re characteristic hya l i n e cyl i n de rs which a re ace l l u lar a n d amphop h i l i c .
Occasionally d u ct- l i ke l u m i n a l i ned b y two cel l layers may also be seen . The tumor
cel l s com mo n ly fo rm th i n cords and trablecu lae s u rro u nded by abundant hya l i n ized
stro m a . Fortu itous planes of sect i o n i n g may reveal peri neu ral spread of the tumor.

1 72

Fig. 79. 5

stroma; T

nest of tumor cel l s ; H

hyal i n e cyl i n der;
N cross section of peripheral ne rve.
-

80. C hronic gastritis

(GAST R I T I S CH RO N I CA)
H e m atoxyl i n -eo s i n
C h ro n i c gastritis may b e auto i m m u ne o r d u e to bacte rial i n fectio n . The so-cal led
ref l u x gastritis i s cau sed by regu rgitated d u odenal fl u i d and b i l e . The fo rmer two
types of gastritis lead to atrophy of the gastric m u cosa, whereas refl ux gastritis is
more apt to be associated with m u cosal hyperplasia.
Gross Findings. In atrophic gastritis the m u cosa i s gray to red , t h i n ner than norma l ,
t h e rugae are f l attened and the s u b m ucosal vei n s are d i sti nct. I n hyperplastic gastritis
the m ucosa i s th ickened , dark red , stiff and appears coarsely co rrugated .
Microscopic Findings. The arch itect u re of the m ucosa is recognizable, but is thinner
pri marily d u e to the decreased n u m be r of c h i ef cel l s . Some of the glands resemble
the crypts of Lieberk u h n of the small i ntesti n e ( i ntestinal metaplasia) . In the i n
terstiti u m there is an i nflammatory i nfi ltrate, with n u mero u s p lasma cel l s and Iym
p hocytes . The plasma cel l s have a sizeable cel l body and eccentric n ucleus. At the
perip hery of thei r cytoplasm, but someti mes also outside the cel l s , homogeneous
eos i n op h i l i c rou n d structu res called Russe l l bodies can be observed . These repre
sent cytoplasmic i m m u noglobu l i n in an aggregated o r altered form . The i nflam mat
ory i nfi ltrate can be local ized to the s u pe rficial layers (superficial type) or can extend
to the entire thickness of the m ucosa (diffuse type).

1 74

Fig. 80. M - gastric glands; Ly - rou nd cell i nfi ltrate.

8 1 . Chronic peptic ulcer

( U LCUS CH RO N I CU M CAL LOSU M VENTR I CU L I )
Aza n
Chronic peptic u l ce r of t h e stomach i s characterized b y the c i rcu m scri bed destruc
tion of the m ucosa and i s accompanied by a n i nflam mato ry i n fi ltrate. Under the
u lcer f i b ro u s tissue is rep lac i n g the t u n i ca m u scu laris p ropria. The i m m ediate cause
of c h ro n i c peptic u l ce r has been attributed to excessive gastric secretion d u e to
several factors. Lately the sign ificance of H e l i cobacter pylori i n fection i n the b reak
down of the m ucus barrier has received m u ch attentio n . Gastric u l cers are most
freq uent in the pyloric reg i o n , but they may occ u r on the cardia, lesser c u rvature o r
othe r sites .
Gross Findings. A 1 -2 cm i n diameter, someti mes larger, u s u a l ly ro u n d m u cosal
defect is see n . The lesion has sharp edges, appears p u nched out and is 0.3 to 0.6 cm
deep. The base of the u l cer is fi rm and covered by friable red to gray tissue debri s .
Microscopic Findings. T h e cont i n u ity o f t h e m ucosa i s i nterrupted a t t h e site o f the
u l cer. The l a m i n a propria i s i nfi ltrated by many rou n d cel l s i n d icati ng an i ntens ive
c h ro n i c i nflam mati o n . The s u rface of the u l ce r ( i nc l u d i n g its base) is covered by
eos i noph i l ic amorphous material . The l u m i n a of the b lood vessels at the base of the
u l ce rs are occ l u d ed . Beneath the s u rface there is vascu lar gra n u l ation tissue with
many f i b rob l asts. In deeper l ayers, i ncl u d i n g the m u scular wal l u nder the u lcer,
there i s marked i ncrease of dense fi brous tissue, i. e . scarri ng, which appears b l u e
w i t h trichro m e sta i n i n d istinction from the m u scu laris p ropria w h i c h i s p u rple. Some
n e rves in the area of the u lcer may show c l u b-l i ke thicke n i n g (trau matic n e u roma) .

1 76

Fig. 81. U

u lcer; N

m ucosa; M

m u scularis propr i a ; H
S granu lation tissue;
-

scar tissue;
detritus.

8 2 . I ntramucosal carci noma of stomach

(CA RC I N O MA INTRA EPITH ELlALE VENTRICULI)
Pe r i o d i c aci d -Sch i ff react i o n , h e m atoxyl i n -eos i n
The development o f gastric carcinoma i s p receded by dysplasia and i ntraepithel ial
(in situ) carci noma of the m u cosa, respectively. Advanced carc i nomas which i n fi l
trate the wal l o f the sto mach have a very p o o r p rognosis. O n the other h a n d , early
gastric carci nomas l i m ited to the m u cosa o r s u b m u cosa can be c u red in up to 90%
of the cases.
Gross findings. Endoscopic exa m i nation shows m ucosal alteratio n s in the areas of
severe dysplasia and carci noma i n s i t u , respectively. These foci appear as s l i ghtly
e l evated o r depressed areas o n the m u cosal s u rface. B i opsies are taken from the
s u spicious areas and thei r m i c roscopic exa m i nation perm its a precise d iagnosis.
Microscopic Findings. The normal gla n d u l a r architect u re i s focally i rregu lar, the
glandu lar l u men and the characeristic cel l s are absent. The m u cosa i s i n u ndated by
atypical cel l s of va riable size, often rese m b l i n g a signet-r i n g ( " s ignet-ring cel l s " ) . I n
these cel l s the i ntracytoplasmic m uc u s com p resses the n u cleus aga i n st the periphery
of the ce l l . The m ucus conta i n ed i n the t u m o r cel l s sta i n s magenta with the periodic
acid-Sch iff react i o n , as are the normal epithelial cel ls of the s u rface and of the pits
of the f u n d i c m u cosa. The tumor f i l l s the t u n ica p ropria but does not i nvade the
s u b m u cosa.

1 78

Fig. 82. Top : H ematoxy l i n-eos i n ; Bottom : Pe riodic acid-Schiff reaction.

gastric glands; C - i n t ra m u cosal carcinoma; S - subm ucosa; P - s i gnet-ring ce l l s ;
N mucus.
-

8 3 . Mucinous adenocarcinoma of stomach

(CA RC I N O MA G ELAT I N OS U M VENTR I CULI)
H e m atoxy l i n-eo s i n , mucica rm i n e
Carci noma of the stomach is one of the most freq uent mal i gnant neoplasms. Pre
d i spos i n g con d itions are c h ro n i c peptic u l cer and atroph i c c h ro n i c gastriti s . D i etary
factors also play an i mportant ro l e : habitual co n s u m ption of d i st i l led alcohol,
smo ked meat o r s m o ked fish contai n i n g coal tar derivatives are risk factors .
Gross Findings. The i nvolved gastric wal l i s co n s i derably th ickened , f i r m , and its
m ucosa is u l ce rate d . On cut s u rface the t u m o r is gray to tan, gelati n o u s , s h i ny and
on p ressu re exudes t h i ck m u c u s . If the tumor penetrates the serosa, it may grow i n
the peritoneal cavity by cont i n u ity a n d may fo rm s i m i l a r gelatinous nodu les there .
So meti mes the t u m o r metastasizes to both ovaries, i n w h i c h case w e speak about a
Kru ken berg t u m o r of the ovaries.
Microscopic Findings. The normal glands of the gastric m u cosa have d i sappeared
and are replaced by i rreg u lar nests of t u m o r . These n ests contain a pale, amorphous
m ucou s extrace l l u lar s u bstance i n which pleomorphic tumor cel l s can be fo u n d . The
cytoplasm of these cel l s conta i n s varying amou nts of m uc u s . The viable tu mor cel l s
have i n tact n uc l e i a n d a f u l l body o f pale cytoplasm, whereas degenerating tumor
cel l s have s h ru n ken (pyknotic) n uclei . Necrotic t u m o r cel l s have no recogn izable
n u clei and the i r cytoplasm can be swo l l e n , amorphous and resembles the extracel l u
lar m u c u s . Special stain for m u c i n ( m u cicarm i ne) demonstrates i ntrace l l u lar as wel l
as extrace l l u lar m uc i n bright red .

1 80

Fig. 83. Top: Hematoxyl i neos i n .

M - regu lar (benign) glands; T - nests o f tumor cel l s ; L y - Iymp hocytes.
Bottom : Mucica rmine.
N muci n ; T - tumor cells.
-

84. Regional enteritis (Crohn's disease)

( E NTE RITIS REG I O NALlS)
H e m atoxyl i n-eosi n
Regional e nteritis i s a c h ro n i c i nflammato ry bowel d i sease of u n known etiology.
It pri marily affects the i l e u m , but can occu r anywhere in the gastro i ntestinal tract,
from the o ral cavity to the a n u s . Abnormal ities of the i m m u n e system and defective
fu n ction of neutro p h i l i c l e u kocytes may play a role in its pathogenesis.
Gross Findings. D i seased bowel segments are alternat i n g with spared ones. The
m u cosa s h ows l i n ear u l cers with hemo rrhagic borders, later these u lcers become
ve rtical fiss u res. The edematou s , i nflamed m u cosal i s lands and deep fiss u res render
a cobble-stone appearance to the m u cosa. As a res u l t of marked chro n i c i nflamma
tion the bowel wal l beco m es t h i ck and f i r m . The l u m e n na rrows and the bowel
resembles a garden hose . Compl i cati o n s i ncl ude perforation or mechan ical obstruc
tion of the bowel o r e nterocutaneous fist u las.
Microscopic Findings. A l l layers of the bowel wal l a re edemato u s and i nfi ltrated by
i nflammatory cel l s . The p red o m i nantly lymphocytic infiltrate is most pronou nced i n
t h e s u b m u cosa, occasionally fo r m i n g lymphOid fol l icles. Deep fiss u res tran sect the
m u cosa and exten d to the t u n i ca m u scu laris p ropria. Characteristic non-caseating
(tuberc u loid) g ra n u lo mas are seen i n the s u b m u cosa and i n the m uscu laris p ropria.
The non-caseat i n g gran u lomas are col lections of modified macrophages cal l ed
epithe l i oi d cel l s a n d of m u lt i n ucleated Langhan s-type giant cel l s (formed by the
coalescence and f u s i o n of epithel i o i d cel ls) . In advanced stages of the d i sease scars
fo rm i n the bowel wal l and lead to obstruction of the Iym phatics . There often i s
epithelial metaplasia o n the s u rface of the i ntestinal v i l l i . Gastric metaplasia with
gastric pyloric gland s , m ucou s cel l s or Paneth cel l s may also be seen in the re
generat i n g epithel i u m a ro u n d the u lcers.

Fig. 84. M

m u cosa of small i ntesti n e ; U - u lceratio n ; F - fissure ;

L - i nflam matory i nfiltrate; I
m u scularis propri a ;
n o n caseat i n g g ra n u loma with Langhan s-type giant cel l s .
-

1 82

85. Acute append icitis

(APPENDI C I TIS ACUTA)
H e m atoxyl i n -eo s i n
I nflam matio n o f the appendix i s a freq uent a n d , becau se of its compl ications,
serio u s d i sease. A n n u a l l y there are 1 00 to 200 fatal cases of appendicitis i n H u ngary
alone. I n the maj o rity of cases appe n d icitis is cau sed by aerobic or anaerobic bac
teria; the l atter can cause gangre n o u s appendicitis. The most seri o u s com p l i cation
of appe n d i citis is perforation and conseq uent perito n i t i s .
Gross Findings. The appendix i s swo l l e n , dark red . Its serosa i s d u l l , covered by
f i b r i n o u s or p u r u lent exudate . I n case of perforation the hole can be fou n d in most
i n stances. U p o n ope n i n g the appe n d i x p u ru l ent exudate pou rs from it and its m u
cosa i s cri m so n .
Microscopic Findings. The l u men i s fi l l ed with amorphous debris, eosi noph i l ic fib
rin fi l aments and large masses of neutrop h i l i c leu kocytes. Basoph i l ic clouds of bac
teria can also be see n . I n c i rcu mscri bed areas the s u rface epithe l i u m and glands of
the m ucosa have been destroyed and rep laced by debris of necrotic tisue. The s u b
m u cosa and m u scu laris p ropria are loose d u e to edema and are densely i nfi ltrated
by polym o rp h o n u cl ear l e u kocytes . Scattered lymphocytic and p lasma cel l infi ltrates
can also be see n . The lymphoid fol l icles of the s u b m ucosa are conspicuously en
larged and the i r ge rm i nal centers are p ro m i n e nt. The serosa i s covered by
eos i nop h i l ic f i b r i n f i l aments and acute i nflammatory cel l s .

Fig. 85A . : Lu - l u m e n ; N - m u cosa; 5 - serosa ; L - fat tissue; P perforat i o n .

Fig. 858. : N m u cosa; I - p u r u l e n t exudate; M - m u sc u l a r wal l .
-

1 84

86. Enterobius vermicularis in appendix

( E N T E R O BIUS VE RMICULA RIS APPENDI C I S)
H e m atoxyl i n -eos i n
The p i nwo rm ( Enterobi u s o r oxy u r i s ve rmicu laris) i s a member of the class of
rou n dworms ( n ematodes) . The eggs reach the gut by the o ral route from a soiled
han d . The i n gested eggs hatch in the d u oden u m , releasi n g larvae that develop i nto
matu re ad u lts, which i n habit the col o n and the appendix. At n ight, the female worms
m i g rate to the a n u s , depositing eggs and cau s i n g the typical noctu rnal pru ritus of
the perianal and peri neal s ki n .
Gross Findings. The ad u l t Entero b i u s i s a small wh ite nematode, 3 to 8 m m long
and 1 .5 to 2 m m in d i amete r . The worms are u s u a l ly seen i n the stool o r attached to
the bowel m ucosa.
Microscopic Findings. The h e l m i nths can be observed in the s u rgica l ly removed
appe n d i x . The nematodes are i n the l u men together with the fecal content or s u per
ficially in the m ucosa. On cross section the ad u l t worms appear rou n d o r ova l , co
vered by a cuticle with two narrow lateral ridges, which on cross section appear as
two character i stic s m a l l spi kes. At the site of the i r m ucosal attachment the parasites
cause small p u n ctate hemo rrhages and m i n ute u lcers, but no sign ificant i nflam ma
t io n . Presu mably, secondary bacte rial i nfection of these sites may cause i nflam ma
tion .

Fig. 86. M m u cosa; N

normal lymphoid fol licles; 5 s u b m u cosa ;
tun ica m u scularis propria; T fecal material in l u men ; F cross section of adult parasite.
-

1 86

F
N
F

87. Ulcerative colitis

(CO L I T I S U LCE ROSA)
H e m atoxyl i n -eo s i n
U lcerative col itis is a c h ro n i c i nflammato ry d isease of the colon and rect u m . Its
etiol ogy is u n kn ow n ; auto i m m u ne and psychic factors may play a rol e in its
pathogenesis.
Gross Findings. I rreg u l arly-shaped confl uent u lcers are seen on the col o n i c m u
cosa. I n severe cases the u l cers may be deeper and extend t o t h e t u n ica m u scu laris
p ropria. M u cosal islands with ma rked chronic i nflam mation may rise above the level
of the m ucosa and become ped u n c u l ated ( i nflammatory pseudopolyps) . Profuse
bleed i ng, malignant transformations o r perforation are the most frequent compl ica
tions.
Microscopic Findings. The re i s a d i ffuse inflammatory infiltrate with i nterm i n gled
polym o rp h o n uclear leu kocytes and Iym p h ocytes, the s u rface epithel i u m and the
l i n i n g of the crypts is destroyed . Ulcers develop which spread ho rizontally and un
dermine the m u cosa. The m ucosa at the edges of the u lcers is edematou s and mar
kedly i nflamed . The m i c roscopic changes reflect the dynamics of destruction and
s i m u ltaneous rege n e ration of the m u cosa. I n the bac kgro u n d of conti n u o u s m ucosal
regen e ration epithelial metaplasia may develop. The m ucus-p rod u c i n g gob let cel l s
d i sappear a n d Paneth cel l s w i l l appear. T h e cont i n u o u s destruction a n d regeneration
of epithel i u m may lead to dysplasia and malignant transformation, t h u s adenocar
ci noma of the colon may arise as a com p l i catio n of c h ro n ic u l ce rative col itis.

1 88

Fig. 87. M

m u cosa; F

u lcer; L

i nflam matory i nfi ltrate; E

blood vessels;
hemor rhage.

88. Tubular adenoma of colon (adenomatous polyp)

(ADE N OMA T U B U LARE CO L I , PO LYP US ADE N O MATOSUS)
H e m atoxyl i n-eos i n
Adenomas are benign t u m o rs of the glan d u lar epithel i u m . I n the col o n i c and rectal
m ucosa adenomas can be solita ry or m u lt i p l e ( po lyposis) as in hered itary syn d romes.
The removal of adenomas i s i n d i cated because they are p recancero u s and adenocar
c i n o mas w i l l freq u e ntly develop i n t h e m .
Gross Findings. Adenomas often a re ped u ncu late d , have a t h i n sta l k t o w h i c h the
head , a spheri cal soft lesio n , 0.4 to 1 .5 cm, is attached . Adenomas are covered by a
velvety tan to red m ucosa. O n cut s u rface the s u pportive co n nective tissue is recog
n izable i n the core of the sta l k and i n the head of the l es i o n .
Microscopic Findings. T h e core o f t h e sta l k con s i sts o f vasc u l ar con n ective tissue
wh ich i s an exten s i o n of the s u b m u cosa of the col o n . The m u cosa of the sta l k i s
non-neoplastic and conti n u o u s w i t h that of the col o n . The head of t h e polyp i s
fo rmed by the a d e n o m a , where the m ucosa i s markedly th ickened , u p t o five t o ten
ti mes that of the norma l . The s u rface of the adenoma i s covered by m u cus-secret i n g
tal l col u m nar cel l s . The adenoma con s i sts of tightly packed long t u b u les w h i c h are
separated from each othe r by t h i n septa of con nective tissue rich in cap i l laries. The
t u b u les correspon d to e l ongated crypts of Lieberku h n ; they may be tortuous or
cystica l l y d i lated . The neoplastic glands are l i ned by a s i n g l e row of regu lar, tal l
co l u m n a r cel l s wh ich stai n pale or darkly. The cytoplasm of the adenoma cel l s con
tai n s an apical m u c i n vacuole, the n uclei are oval o r elongate, hyperchromatic and
located n ear the base of the cel l s . Several m itotic figu res are see n . The p ro l iferating
col u m nar cells may pile up, beco me pseudostratified and the glan d u lar l i n i ng may
be u n even . The basement m e m b rane is wel l preserved and d i stinct everywhe re . The
l u men of the glands may contai n fai rly basoph i l ic , vei l - l i ke m uc u s . The stroma of the
polyps shows some ro u n d cel l i nfi ltrate s , occas i o n a l ly small foci of hemo rrhage and,
sometimes, hya l i n izat i o n .

1 90

Fig. BB. K

core of s u pportive con n ective tissue; M adenomato us glands;

H
muci n-secreti ng col u m nar cel l s .
-

89. Acute viral hepatitis

( H EPATITIS ACUTA VIROSA)
H e m atoxyl i n -eo s i n
More variants of v i r u ses ( hepatitis A, B , C o r no n-A, non-B, 0, and E) have been
i m p l icated in the etiology of this i nflammatory d i so rder. The co u rse of hepatitis is
q u ite variable d epen d i n g on the type of virus and on the immune response of the
affected perso n . The d i sease may have o n ly m i ld symptoms and be anicteric; at the
othe r end of the spectru m , it may be f u l m i nant with massive hepatic necrosis and
fatal .
Gross Findings. The l iver i s en l arge d , its caps u l e i s smooth . The free edges of the
l iver a re rou nd e d ; on cut s u rface its s u bstance is friable, tan to red .
Microscopic Findings. I n hepatitis B there is evidence of i nflam matio n t h roughout
all l o b u l e s . The fol lowi n g are the most str i k i n g changes : (1 ) Necrosis and s i m u l tane
ous regeneration of hepatocytes (2) Inflammatory infiltrate in the portal connective
tissue and in the i ntralobular parenchyma (3) Hyperplasia of Kupffer cells with an
i n crease in thei r phagocytic activity. The cel l plates of the l iver are i rregu lar, de
fo rmed . I n the cytoplasm of i n d iv i d u a l hepatocytes, there are fine gran u les of yel low
b i l e pigment. Pri mari ly the centri l o b u l a r hepatocytes are destroyed (unicellular nec
rosis). So-cal led ballooned hepatocytes may occ u r ; these cel l s are swo l l e n , two o r
th ree ti mes the size of normal and have gra n u lar, pal e-sta i n i n g cytoplasm . Bal looned
cel l s die by cytolys i s . Another form of cel l necrosis i s by formation of acidophilic
bodies ( Co u nc i l man bodi es) : the n u cleus of the damaged cel l becomes pyknotic
and d i sappears, the cytoplasm s h ri n ks and a n ecrotic cel l becomes a deeply
eosinoph i l ic rou n d body. In the vicin ity of destroyed cel l s a sign of early regenera
tion are the newly fo rmed hepatocytes . The recently regenerated hepatocytes have
darker n uclei and thei r cytoplasm has a basoph i l ic h u e . B i n uclear hepatocytes and
m itotic ones can also be see n . The portal areas are en larged , loosely edemato u s and
i nf i ltrated by inflammatory cells. The i nfi ltrate co n s i sts mai n ly of Iymphocytes and
h i stiocytes, with a n ad m ixt u re of eos i n o ph i l ic and neutro p h i l i c polymorphonuclear
l e u kocytes. A s i m i l a r cel l u lar i nf i l t rate i s seen with i n the lobu les, pri mari ly aro u n d
the central vei n s . There i s an i ncrease i n t h e n u mber of Kupffer cells and thei r i n
creased phagocytic activity i s i n d i cated b y i ntracytoplasmic l i pofu sci n a n d i ron-con
tai n i n g pigment, which are derived from n ecrotic hepatocytes and eryth rocytes , re
spectively.
With the orce i n sta i n ( S h i kata reaction) o r i m m u noh i stoch e m i ca l ly the s u rface
antigen of the hepatitis B virus ( H B sAg) can be demon strated i n the cytoplasm of
i n d ividual h epatocytes .

1 92

Fig 89. I - i nflam matory i nf i l trate : M - i r reg u l a r pl ates o f l iver cel l s ;

C - Counci l m a n (acidop h i l ic) bodies; P - i nt race l l u lar b i l e pigment;
balloo n i ng dege n e ration of hepatocytes; R regenerat i n g hepatocyte.
-

90. Chronic hepatitis

( H EPAT I TIS C H RO N I CA)
H e m atoxyl i n -eosi n , o rce i n
Chronic hepatitis i s a cont i n uo usly progressive d i sease which has a n asymptomatic
begi n n i ng and in severe cases may l ead to hepatic ci rrhosi s . In its etio l ogy viral
hepatitis (B, C), auto i m m u n e p rocesses and the side-effect of some d rugs has to be
co nsidered . C l i n ica l l y and h i stopatho l ogi cal ly the d i sease may have m i l d , moderate
or severe stages and tran sitional forms can also occ u r .
Gross Findings. The l iver i s en large d , f i r m , red t o b rown .
Microscopic Findings. I n mild cases of c h ro n ic hepatitis the regular lobular architec
t u re is p reserved . The portal tracts are widened and i nfiltrated by ro u n d cel l s . The
te r m i n a l plates a re i n tact, no i nflammato ry i nf i ltrate is seen between the l iver cel l s .
I n the vicin ity o f t h e i nflammatory reaction t h e hepatocytes are moderately dam
age d , their cytoplasm is swo l l e n , f i nely gra n u lar, l i ghtly eos i noph i l i c . I n hepatitis B
v i r u s i nfection the cytoplasm of some h epatocytes sta i n s l ightly and has a homogene
ous gro u n d-glass appearance. These cel l s may be scattered s i ngly or fo rm smal l
gro u ps and are rich i n hepatitis B virus s u rface antigen ( H BsAg) . The cytoplasm of
the gro u nd-glass h epatocytes sta i n s dark red-b rown with o rcei n (Shikata reaction);
the H BsAg also can be demonstrated i m m u n o h i stochem i ca l l y . An i ncreased n u mber
of Kupffer cells with p hagocytized i ntracytoplasmic b rown gra n u les of hemosideri n
and l i pofu sci n are also n oted .
I n severe forms of c h ro n i c hepatitis the portal tracts are i nfi ltrated with Iympho
cytes and plasma cel l s . The i nflammatory ce l l s have b roken t h rough the l i m iting
plate and a re also p resent i n small groups with i n the parenchyma. The l iver paren
chyma at the edge of the portal tract (the l i m i t i n g plate) is eroded and infi ltrated by
c h ro n i c i nflammato ry cel l s . The damaged h epatocytes have an u neve n , moth-eaten
appearance which is referred to as piecemeal-necrosis. I n advanced cases the nec
ros i s extends i nto the l o b u l e s and l i n ks the te rmi nal hepatic ven u les (central veins)
to the portal tracts ; this i s referred to as bridging necrosis. Eventually the necrotic
hepatocytes are rep laced by n ewly formed connective tissue septa, which divide the
hepatic l o b u les and s u rro u n d s m a l l i s lands of l iver parenchyma . Extensive destruc
tion of hepatocytes i s fol l owed by nod u lar regeneration which l eads to the develop
ment of ci rrhos i s .

Fig. 90A . a n d B . L

portal tract with i nflam matory i nfiltrate; Z - l i m i t i n g plate ;

D damaged hepatocytes; T - gro u nd-glass h epatocytes.
Fig. 90C. Orce i n ( S h i kata reacti o n ) .
H - H BsAg i n h epatocytes.
Fig. 900. a n d E. L lymphocytic i nf i l t rate extend i ng i nto parenchyma;
D damaged hepatocytes ; N p i ecemeal-necros i s .
-

1 94

T
L

.
. ,
a

I..

I
-.

..

.- \.

...

N
L

L
D

9 1 . Alcoholic hepatitis
( H EPAT I T I S ALCO H O LlCA)
H e m atoxy l i n -eos i n , Mal l o ry's trich ro m e
C l i n ical a n d experi m ental data have p roven t h e potentially hepatotoxic effect of
ethyl alcohol which p r i ma r i ly damages the l i p i d metabolism of l iver cel l s .
Gross Findings. T h e l iver i s en larged , yel l ow , has a greasy sheen a n d fee l s fi rm d u e
t o f i b rosis.
Microscopic Findings. The characteristic features of alcoholic hepatitis are damage
and necrosis of hepatocytes, focal collections of neutrophilic leukocytes, and in
creased collagen (fi b ros i s ) . The changes are most p ro m i n ent i n the center of the
l o b u l es . In the cytop lasm of many hepatocytes large vacuoles may be seen which
correspond to the fat glob u l es d i ssolved d u ri n g tissue em bedd i n g . The centri lobu lar
hepatocytes are swo l l e n , have abu ndant pale-sta i n i ng cytoplasm, their outli nes are
i n d i st i n ct. I n the cytoplasm of some hepatocytes Mallory bodies (also cal led al
coh o l i c hya l i n ) can be see n , which are horseshoe-shaped strands o r peri n uclear
r i n gs of eos i noph i l i c , homoge n o u s , dense material . Less frequently Mallory bod ies
can be seen as rou n d ed structu res eccentrically located in the peri n uclear cyto
p lasm . Electron m icroscopica l l y Mal l o ry bodies are com posed largely of b u n d les of
1 4-15 n m t h i ck i ntermed iate fi l am e nts of the cytoskeleton . These bod i es can be
fou n d i n cel l s which appear i n tact, and also i n dyi n g cel ls with pyknotic n u clei . After
d i s i ntegration of the h epatocytes the Mallory bodies can be observed i n the extracel
l u lar space. The damaged hepatocytes and M a l l o ry bod ies are feq uently s u rrou nded
by small col l ecti o n s of i nflammatory cel l s , mai n ly neutrophilic leukocytes. The
changes in the parenchyma are acco m pa n i ed by a mesenchymal reaction. There i s an
i n crease in Ku pffer cel l s and grad u a l l y col l agen fi bers are laid down aro u n d the
central vei n s . Characteristically in the centri l o b u l a r zone i n d ividual hepatocytes are
s u rro u n ded and separated by co l lagen fibers (pericellular fibrosis), which can be
wel l demon strated with co n n ective tissue sta i n s .

1 96

Fig. 9 1 . L

leu kocytic infiltrate; H - hepatocytes; V l i p i d vacuoles; F - fibrosi s ;

M - alcoholic hya l i n (Ma llory bod ies) .
-

92. Micronodular cirrhosis

( CIRR H OSIS MICRO N ODU LARIS H EPATI S LAE N N EC)
Mal l o ry's trich ro m e , h e m atoxyl i n -eos i n
H epatic ci rrhos i s i s a slowly p rogressive d i sease which cau ses portal hypertension
and i n su fficient fu n ction of the l iver. I t occu rs in i n d ividuals who have a h i story of
alco h o l i s m , hepatitis B o r C , c h ro n i c gastro i ntesti nal d i so rders o r mal n utrition.
Gross Findings. The vo l u me of the ci rrhotic l iver i s sign i fi cantly d i m i n i shed, u p to
half of the origi n a l . I ts s u bstance is q u ite to u g h , och re o r tan . The s u rface of the l iver
i s u neve n l y n o d u l a r with 0.3 to 0.8 cm . hemisphe rical p rotu berances separated by
retracted sca r tissue. O n cut s u rface the normal l o b u l a r architect u re is grossly d i s
torted a n d transformed.
Microscopic Findings. There i s comp lete tran sfo rmation of the lobular arch itecture
d u e to increase in connective tissue and destruction of parenchyma with simultaneous
regeneration. The n ewly formed t h i ck septa of con n ective tissue divide the l iver
pare nchyma i nto i s lands of i rregu l a r shape and variable size, fo rming so-cal led
pseudolobules. Central vei n s are o n l y occas i o n a l l y seen and then they are not in the
center of the pseudol o b u les. The normal rad ial arrangement of cel l plates i s absent.
I n stead, spared, damaged, regenerat i n g o r newly fo rmed hepatocytes are seen in
the pse u d o l ob u l es . S ma l l , atro p h i c h epatocytes can occ u r, and the destruction of
single hepatocytes i s occas i o n a l ly also see n . These dead hepatocytes can be recog
n ized by the i r characteri stics : homogeneo u s , deeply eosi noph i l ic and ro u nd i n
structu re (they are also known a s acidop h i l i c bodies o r Counci l man's bodies) . S i m u l
taneously hepatocytes regenerate a n d form t h i c k , i rreg u l a r plates or i s lands of
hyperp lasia. The n uc l e u s of rege nerat i n g hepatocytes is frequ ently polyp l o i d , hyper
c h romatic, often b i n u cl eate o r m u lt i n uclate . The cytoplasm of regenerati ng hepato
cytes sta i n s darke r than u s u a l , someti mes it has a basoph i l ic h u e . The i rregu lar re
gen e ratio n of the pare nchyma i nterferes with the drainage of its b i l e secretion and
its b l ood s u pply, thus b i l e pigment and l i p i d vacuo les may be seen i n the cytoplasm
of the h epatocytes . The pseudolob u les are separated by thick septa of co n n ective
tissue rich i n col l agen fibers. These se pta are i nfiltrated by inflammatory cells ( lym
p hocytes, plasma cel l s , n eu trop h i l ic l e u kocytes ) . The septa also conta i n many newly
formed bile ductules which are tort u o u s , someti m es b ranch i n g to resemble a stag
horn ; the d u ct u l e s are l i n ed by c u boidal epithel i u m .

1 98

Fig. 92A . Top : Mal lory's trich rome.

K - connective tissue; P - pseudolobules.
Fig. 928. Bottom : Hematoxy l i n - eos i n .
V - l i p i d vacuoles; H - dest royed hepatocytes.

93 . Hepatocellular carcinoma
(CARCI N O MA H EPATO CELLULARE)
H e m atoxyl i n -eos i n , o rce i n
H e patoce l l u l a r carci noma i s by far the most com m o n pri mary mal ignant tumor of
the l iver. D i etary components (aflatoxi n B ) , besides ci rrhos i s and chronic hepatitis B
and C v i ral i nfection play an i m portant role i n its pathogenesis.
Gross Findings. There may be a s i ngle, large, 5 .0 to 20 cm in diamete r, c i r
cu mscribed mass, o r scattered nod u l es s u ggestive of m u lticentric orig i n . The l atter
i s com mo n l y seen in ci rrhotic l ivers . More seldom the tumor i s vol u m i nous and
i nfi ltrates the l iver parenchyma without sharp borders. On cut s u rface the tumor is
soft, gray to yel low o r gree n i s h , depe n d i n g o n its capabi l ity to p roduce b i le .
Microscopic Findings. Hepatoce l l u lar carc i n omas may be wel l-d ifferentiated or u n
d i fferentiated (anapl astic) . T h e cel l s o f well-differentiated tumors resem b l e hepato
cytes , are po lygon a l , t h e i r abu ndant cytoplasm is b ri ghtly eosi noph i l ic . The cyto
p lasm may conta i n b i l e pigment, l i pid vacuoles and occasional Mallory bod ies. The
t u m o r cel l n uclei are ro u nded, variable in size, shape and ti nctorial properties. Dif
ferentiated hepatoce l l u lar carc i n omas most often have a trabecular arch itect u re . The
t u m o r cel l s are o rgan ized in i rreg u l ar plates, one cel l o r m u lt i p l e cel l s thick, however
they do not fo rm l o b u l es . Between the plates of t u m o r cel l s there are s i n u soids l i ned
by flat e ndothel ial cel ls . The stroma is sparse, portal spaces o r b i l e d ucts are not
see n . I n freq uently a pseudoglandular patte rn can be encou ntered, when the tumor
cel ls are form i n g struct u res rem i n i scent of i rreg u l ar glands. A rare type of hepatocel
l u l a r carci noma i s com p osed of cel l s with a clear cytoplasm, also cal led hyperneph
roid carcinoma. The cytop lasm of these cel l s is swo l l e n and water-clear because of
the i r abu n dant glycogen and l i p i d content. The cel l s of undifferentiated hepatomas
are h ighly variable i n size and shape; thei r n uclei are large, hyperc h romatic, have
scant basoph i l ic cytoplasm, b izarre, gigantic m u lti n u cl eated tumor cel l s and abnor
mal mitoses are freq uent. The t u m o r cel l s fo rm gro u ps of variable shape and size.
The cel ls of some h epatoce l l u lar carci n omas are positive for the S h i kata reaction
(orce i n sta i n for hepatitis B s u rface antige n ) .

Fig. 93. Top and Botto m , left : Hematoxyl i n -eos i n .

P pseu dolob u l e ; T - nest o f t u m o r cel l s ; 5 - conn ective tissue sept u m ;
L - lymphocytic i nfi ltrate; H - hyperchromatic n u c l e i ; M - m u l ti n u cleated t u m o r cel l .
Bottom, r i g h t : O rcei n ( S h i kata reaction) .
0 - orce i n-posi tive tumor cel l s .
-

200

94. Benign neph rosclerosis

( N EPH ROSCLE ROSIS BEN I G NA)
H e m atoxyl i n -eos i n , van G i eso n ' s e l asti n
Benign neph roscle ros i s is the name give n to renal changes associ ated with ben ign
hyperte n s io n .
Gross Findings. T h e k i d neys are s u bstantially reduced i n size. The f i b ro u s capsule
strips with d ifficu lty, the s u rface of the k i d n eys i s evenly f i nely gra n u lar. The kidneys
are b rown to red , fi rm and o n cut s u rface the co rtex i s markedly t h i n ned.
Microscopic Findings. The most characteristic change of benign nephroscleros is i s
hyaline sclerosis of the medium-sized and small arteries. T h e wal l of these vessels i s
markedly t h i c k e n e d , homogeneo u s , eos i noph i l ic . Their l u men i s narrowed and the
d i m i n i shed b lood flow res u lts in the ische m i c changes . The n arrowi n g o r occl usion
of the afferent a rterioles i m pedes o r stops perfu s i o n of the glomeru l i . The glomeru
lar loops co l l apse and become occl uded. Col lagenous material completely fi l l s Bow
man's space, and periglomerular fibrosis develops. Ultimately, scattered glomeru l i
co m p l etely hya l i n ize a n d become homogeneous eos i no ph i l i c spheres (glomerulo
sclerosis). The interlobular arteries show i ntimal thicke n i n g of the fi broelastic type.
Th e re is red u p l i cati o n of the l a m i n a e lastica i nterna with the appearance of several
concentric layers of e lastic l a m i n ae (lamellar elastosis). Special sta i n s demonstrate
concentric wavy elastic fibers i n the th ickened wal l of the arte ries. The tubules may
be atrophic and are rep laced by i ncreased i n te rstiti u m . A m i ld lymphocytic i nfi ltrate
is seen i n the i n te rstiti u m .
Immunofluorescence and electron microscopic findings i n d icate that the hya l i n e sub
stance in the arte rial wal l s conta i n s p l asma p rote i n s and l i pids. These substances
enter the a rterial wal l s and deposit there because the endothe l ial l i n i n g has been
damaged by hyperte n s i o n .

202

Fig. 94. Top : He matoxyli n-eosi n ; Bottom : van G i eson's elasti n .

G - glomeru l i ; T - t u b u les; I
i nterstiti u m ; A small arte ries; E - elastic fibers.
-

95 . Acute diffuse prol iferative glomerulonephritis

( G L O M E RULON EPH RITI S ACUTA DI FFUSA)
H e m atoxyl i n -eos i n
Acute post-streptococcal glomeru l o n e p h ritis i s a fai rly frequent renal d i sease. Pre
s u mably i m m u n o l ogic p rocesses play a ro l e in its pathogenesis. Most patients have
a raised anti-strepto lys i n titer, and there is a sign ificant red uction in seru m comple
ment l evels which s u ggests that the com plement system mediates the i m m u ne re
sponse.
Gross Findings. The k i d n eys appear s l i ghtly swo l l e n , their capsu l e i s tense and peels
off with ease. The kidneys have a smooth s u rface, are pale tan to red-brown and
show dark red petech i ae resemb l i n g flea b ites. The parenchyma i s moist, fragi le. On
cut s u rface the co rtex i s widened and pal l i d , the m ed u l la is d us ky p u rple.
Microscopic Findings. The most i m portant characteristic of acute d iffuse glomerulo
nephritis i s the e n l argement of glomeruli which become hyperce l l u lar, b loodl ess and
fi l l Bowman's space. The en largement is due to the p ro l ife ration and swe l l i n g of
endothelial and mesangial cells, l ess com m o n l y the epithelial cel l s of Bowman's cap
s u l e are also swol l e n and p ro l iferate. These glomeru lar changes are accom pan ied by
an i nflammatory i nfi ltrate, m a i n ly of polymorphonuclear leukocytes. I n some
glomeru l i the swe l l i n g and prolife ration of the endothe l i a l cel l s i s marked and com
pletely obstructs the cap i l l aries , the glomeru l i becom i n g b loodless. In the narrowed
space of Bowman's capsu l e coag u l ated eos i n oph i l ic plasma, p recipitated fibri n ,
l e u kocytes a n d e ryth rocytes may b e see n . The epithelial cel l s o f the proximal convo
luted tubules are swo l l e n , some lose thei r n u clear stai n a n d , i n more severe cases,
may be detached. The l u m e n of the d i stal convo l u ted t u b u les and of the co l lecting
t u b u l es con ta i n s gra n u lar cyl i n ders which co nsist of debris from detached epithelial
cel l s , polym o rp h o n u cl ear l e u kocytes and e ryth rocytes. The l u men of some convo
l uted t u b u les is fi l led with fresh blood. The interstitium i s loose, edemato u s and
s l ightly i n f i ltrated by ro u n d cel l s .
Immunofluorescence microscopic stu d i es demonstrate l a rge, gran u lar deposits of
I gG and com plement protei n C3 on the basement membranes of glome r u l i and
with i n the mesangi u m .
Electron microscopic exam i nation reveals amorphou s , e lect ro n-dense i m m u n e
com p l exes deposited between t h e epithel i u m a n d t h e basement membrane.

204

Fig. 95. G

glomeru l u s ; T

tubule; I

i ntersti t i u m .

96. Membranoproliferative (mesangiocapillary)

glomeruloneph ritis
(GLO M E R ULO N EPH RITIS M E M BRAN OPROLl FE RATIVA
[M ESAN G I OCAP ILLA R I S] D I FFUSA)
Pe r i o d i c aci d-Sch i ff react i o n , i m m un ofluo resce nce study
a n d e l ect ro n m icro scopy
Membranopro l i ferative glomeru lonephritis is seen most com m o n l y i n chi l d ren
and you ng ad u lts. Some cases are id iopat h i c , oth e rs a re associated with known d i s
eases (e. g. bacte rial endocard itis, c h ro n ic active hepatitis , ci rrhosis, post-transplan
tation rejection reaction , auto i m m u ne d i seases) . C l i n ically it often p resents as a
neph rotic synd ro m e a n d , i n about half of the cases, it grad u a l ly leads to chronic
renal fai l u re .
Gross Findings. N o characteristic changes .
Microscopic Findings. A l l glomeruli are markedly en larged , most are hyperce l l u lar
and s how an accentuation of the l o b u les. There is an i ncrease in the amo u nt of the
mesangial matrix as wel l as mesangial cells. The i rregu lar, u neven th icken i n g of the
glomerular basement membrane is wel l demonstrated and parti cu larly d i sti nct with
the PAS reaction o r J o n es' methenam i n e si lver sta i n . These changes are often accom
panied by an i nflam matory i nfi ltrate of polymorphonuclear leukocytes and mono
nuclear cells. I n long-stan d i n g renal d i sease there is a marked i ntimal thicken i n g i n
the small arteries d u e t o hya l i n e scleros i s . Moderate t u b u l a r atrophy occu rs d u e to
the i m pai red b l ood s u pply. Interstitial i nflam matio n with scattered Iymphocytes and
some i ncrease in co n nective tissue also can be observed .
Immunofluorescence microscopy shows gra n u lar- l i n ear deposits of C3 along the
glomerular basement m e m b rane.
Electron microscopy demonstrates t h i cken i n g of the cap i l lary basement membrane
with l a rge deposits of homogeneous e l ectro n-dense material.

206

Fig. 96A a n d B . G - G lomeru l u s ; B - Bowman's capsu le;

BM - Cap i l l ary base ment membrane; M - mesang i u m ; T - t u b u l es; D - l i near-gra n u l a r deposits.
Fig. 96C. L - cap i l lary l u me n ; BM - basement membra n e of cap i l la ry ;
D - electron-dense depos it; E - endothelial cel l .

97. Chronic pyeloneph ritis

(PYELO N EPH R I TIS CH RO N I CA)
H e m atoxy l i n -eos i n
C h ro n i c pyeloneph ritis i s a very co m m o n i nflammatory d i sease of the kid neys ,
which develops as a resu l t of asce n d i n g ( refl ux) or hematogen o u s bacte rial i nfectio n .
T h e grad u a l destructi on o f renal parenchyma b y i n fection wi l l lead t o renal i n suffi
ciency, which may develop rap i d l y when the d i sease i s associated with severe hyper
ten s io n .
Gross Findings. The vol u m e o f the kidneys i s d i m i n i shed, their capsu l e strips with
d iffi c u lty, the s u rface s h ows n u merous i rreg u l a r gross, depressed flat sca rs. Scarring
i nvolves not o n ly the cortex, but also extends to the med u l la and calyceal syste m ,
therefore t h e renal pap i l l ae and calyces may be defo rmed . T h e m u cosa o f t h e renal
pelvis i s gray-wh ite and t h i ckened .
Microscopic Findings. The most stri k i n g changes are seen i n the tubules. Some renal
t u b u les are hypert ro p h i c , others are atro p h i c and d i l ated . The d i lated tubu les are
l i ned by flattened epithel i u m and the i r l u men i s fi l l ed with eosi noph i l ic cyl i nd rical
casts, so that some parts of the med u l l a m ic roscopica l ly resemble thyroid tissue
( "thyroidization "). The i nterstiti u m of the co rtex as wel l as of the med u l la is i nfil
trated by rou n d cel l s . Depe n d i n g o n the d u ratio n of the d i sease the connective
tissue fi bers are i n creased . If s i m u ltaneously an active i nfection is also p resent,
polymorpho n u cl ea r leu kocytes are i nter m i ngled with Iym phocytes in the i nterstitial
i nfi ltrate . Pus cel l s and l e u kocyte casts are also seen i n the l u men of the col lect i n g
d ucts . I n itial ly the glomeruli a r e l e s s affected, however, i n later stages of the d i sease
periglomerular concentric f i b ro s i s develops, and conti n u o u s damage leads to
hya l i n ization of glomeru l i . These glomerular changes are a com p l i cation of hyper
tensive vascular d i sease.

Fig. 97A . P periglomerular f i bros i s ; G glomeru l i ; I

i nterstitial i nflam matory i nfi ltrate.
Fig. 97B. C proteinaceous casts; H hya l i n ized glomeru l i ; 1 - i n terstitial i n flammatory infi ltrate.
-

208

98. Diabetic glomerulopathy (Kimmelstiel-Wilson syndrome)

(GLO M E R U LOSCLEROSIS I NTE RCAPI LLA R I S)
H e m atoxyl i n eosi n , Mal l o ry's trich ro m e
Ove r t h e years diabetes m e l l it u s causes man ifo l d severe changes o f the kid neys .
Among these a re arteriolar hyal i nosis, renal pap i l lary necrosis and d iabetic
glomerulopathy. G l omeru losc l e rosis d evelops 1 0 to 1 5 years after the o nset of d iab
etes. C l i n i cally it p resents as a neph roti c syndrome, with grad u a l l y developing renal
fai l u re ( K i m m e l stiel-Wi l so n syndrome) .
Gross Findings. The kidneys appear s l i ghtly en larged , tan to brown . I n advanced
stages the i r s u rface is f i nely gra n u lar, d u e to cortical scarri ng.
Microscopic Findings. G lomeru l osclerosis can be d i ffuse o r nodular and both
changes may occ u r together i n a glomeru l u s . I n diffuse glomerulosclerosis the glome
ru l i s how a stri k i n g l o b u l a r arch itect u re . The mesangial matrix is expanded and de
pos its of ho mogeneo u s , ace l l u l a r eos i noph i l i c mate rial are seen in it. S i m u ltaneously
the basement m e m b rane of the cap i l l aries i s th ickened and their l u men is narrowed.
Diffuse glomeru l osclerosi s may be a com p l i cati on of vari o u s vascu lar d i seases, b ut
nodular glomerulosclerosis al most exc l u sively acco m pa n ies diabetic neph ropathy. I n
nod u l a r glomeru l osclerosis spherical o r pear-shaped , homogeneous eos i no p h i l i c
n o d u l es of variable s ize a r e seen i n t h e mesan g i u m a t t h e periphery o f t h e glomeru l i .
The capi l l aries o f the l o b u l e are d i sp laced b y the nodu les and often wrapped aro u n d
t h e m l i ke a wreat h . T h e homogeneous material seen i n both d iffuse and n o d u l a r
forms i s PAS positive and m u copolysaccha rides and l i pids c a n be h i stochemically
demon strated i n them . With time these changes p rogress with i n a glomeru l u s and
wi l l also i nvo lve more glomeru l i . F i n a l l y the l u men of the capi l laries i s occl uded and
the e nti re glomeru l u s co n s i sts of hya l i n e n o d u l e s . There i s also hya l i nosis of the
affe rent and efferent arte rioles. As a con seq u ence of glomerular damage and renal
ischemia t u b u lar atrophy and i ncrease of i nterstitial tissue is seen .

Fig. 98. G glomeru l u s ; T t u b u l e ; C- cap i l l a ry loops ;

S
i ntercapi l l a ry sclerosis (Kim melstiel-Wilson nod u l e ) .
-

210

99. Renal tubercu losis

(TU BE RCULOSIS RENIS)
H e m atoxyl i n -eos i n
Renal tubercu losis may develop as a resu l t of hematogenous spread of Mycobac
ter i u m tu berc u losis. The m i c roorga n i s m s reach the k i d n eys via the b lood stream
from the site of p r i mary p u l m o nary tubercu losis. Renal t u be rcu losis may also devel
op as a n ascending i n fection from tuberc u l o u s cystit i s . I n such cases i n fection of the
contralateral k i d n ey may be the sou rce of bacteria in the u ri n e . Rarely tubercu los i s
of the rep roductive system ( p rostate, epid idym i s) m a y extend t o t h e u ri nary b ladder
and lead to an asce n d i n g i nfection of the k i d ney.
Gross Findings. S m a l l yel low fi rm g ran u l omas are seen in the renal parenchyma.
On cut s u rface these lesions have a cru m b l i ng caseou s center . Some gran u lomas are
confl u ent and form larger lesions. In advanced cases, the renal pyramids have been
destroyed and replaced by ragged cavitary lesions f i l led with caseo u s , necrotic tissue
(phth i s i s ren a l i s tubercu l osa) .
Microscopic Findings. Rem nants of i nvol ut i n g glomeru l i and of renal tubu les can
be recogn ized . Characte ristic tu bercles are seen i n the damaged renal parenchyma.
I n the center of these areas caseati n g n ecrosis i s see n , which is eosinop h i l ic and
amorph o u s . The areas of caseating necrosis are s u r ro u n ded by a zone of epithelioid
cel l s and Langhans type giant cel l s . The epitheloid cel l s are modifi ed macrophages
and have an oval n uc l e u s and fai ntly sta i n i ng cytoplasm. Langhans type giant cel l s ,
fo rmed b y the f u s i o n o f epith e l i o i d ce l l s , have m u lt i p l e smal ler oval n uclei arranged
in a wreath at the peri phery of the abu ndant cytoplasm. The tubercles are s u r
rou n ded by a lymphocytic and p lasma cel l u la r i nfi ltrate . The i nterstiti u m shows an
i n crease i n con n ective tissue fi bers (fibrosi s) which is i nfiltrated by chronic i nflam
matory cel l s .

212

Fig. 99. G - glomer u l u s ; G t - tuberculous gra n u l omas;

Langhans type giant cel l s ;

L - i n flammatory i nfi ltrate.

1 00. End stage renal disease

H e m atoxyl i n -eo s i n

N u m e ro u s renal d iseases ( e . g . vari o u s fo rms of glomerulonephritis, pyelonephri

t i s , neph rosclerosis) can lead to the development of so-called e nd-stage renal d i s
ease. At t h i s stage m icroscopic stu d i es w i l l not be able to d i sclose the cause of the
renal changes. C l i nically renal fu nction grad u a l l y ceases and without med ical i nter
vention (dialys i s , renal tran splantation) u re m i a w i l l lead to deat h .
Cross Findings. The k i d neys a r e markedly s h ru n ke n . T h e s u rface of t h e kid neys
may s h ow finer or coarser gran u la rity as wel l as larger i rregular deeper scars. On cut
s u rface the cortex and m ed u l l a are stri k i ngly t h i n and there i s compen satory i ncrease
of the peripelvic ad i pose tissue. The cortico m ed u l lary j u n ction is i n d i st i n ct.
Microscopic Findings. In the cortex the glomeru l i are replaced by sparsely cel l u lar
hyal i n e spherules. Occasionally some partly recogn izable glomeru l i are p resent. The
majority of t u b u les has been d estroyed and replaced by a scar of hya l i n ized connec
tive t i s s u e infiltrated by Iymphocytes and p l asma cel l s . Also i n the m ed u l la, between
the co l lect i n g t u b u l es there is sign ificant scarri n g of the i n terstiti u m . The wal l of the
small and med i u m-cal i be r arteries is markedly th i ckened and hyal i n ized . The arterial
l u men may be occl u ded at several poi nts by s u b i ntimal fibros i s . The vei n s are mod
erately d i l ated and congested .

214

Fig. 100. G

hyal i n ized glomeru l u s ; T

t u b u l e s ; A artery; V vei n ;
L y - lymphocytic i nf i ltrate.
-

1 0 1 . Renal cell carcinoma

(CA RC I N O MA H YP E R N EPH RO I DES REN I S)
H e m atoxyl i n -eos i n
T h i s t u m o r occ u rs i n m i d d l e-aged and elderly i ndividual s ; i t i s more common i n
men . Recently c h ro m osomal abnormal ities have been demonstrated i n certain types
of t h i s t u m o r . The t u m o r is asymptomatic for a long t i m e and when it p resents with
hemat u ria, it has exten ded i nto the renal pelvis and often also i nto the renal vei n .
Metastases. are most frel uent t o the l u ngs, l iver, bones and s k i n .
Gross Findings. I n t h e s u bstance of t h e k i d n ey, u s u a l ly a t o n e pole, there is a gray
to tan foca l ly hemo rrhagic and necrotic, moderately firm t u m o r which i n itially is
demarcated but I'a ter grows i nfi ltratively. In advanced stages the tumor may attai n a
d i a m eter of 1 5 to 20 c m .
Microscopic Findings. I n t h e majority o f cases t h e t u m o r cel l s form nests a n d b u n
d les, occasi o n a l ly also gland-l i ke struct u res. The t u m o r cel l s are large and rich i n
glycogen which d i ssolves i n t h e cou rse o f p reparation o f the s l i de, therefore thei r
cytopl'asm appears optica l ly em pty a n d clear, s i m i lar t o that o f p l a n t cel l s . The ap
pearance and sta i n i n g of the t u m o r ceHs i.s fai rly u n ifo r m . The n u clei are sma l l , m ito
tic activity is see n . I n some areas the t u m o r i nvades the adjacent renal parenchyma,
in othe r areas, the grow i n g t u m o r p ushes the renal, stroma to form a fibro u s capsu l e
l i ke structu re . Freq u e ntly the t u m o r cel l s are seen i nvad i n g b l ood vessel s , i ndicative
of a part i c u l arly lI nfavo rab l e p rogno s i s . A smaUer gro u p of re nal cel l carci nomas i s
com posed of cel l's w i t h eos i n o p h i l'ic o r basoph i l i c cyto pl asm . Basop h i l ic renal cell
ca-rei-nomas. are mostly papi l l'ary and l ess aggressive. O n cocytic renal tu mors are very
rare and l i kewise less aggressive.

21 6

Fig. 101A. T

tumor; P

pseudocaps u l e ; V renal parenchyma; E l u m en of blood vesse l ;

Fig. 101B. T tumor cells; K con n ective tissue septum.
-

102. Papillary transitional cell carcinoma of urinary bladder

(CARCIN O MA PAP I L LA R E VESICAE U R I NARIAE)
H e m atoxyl i n -eos i n
Pap i l lary carci noma of the b ladder u s u a l l y develops from benign pap i l l omas. I n its
etio logy local i rritation (stones, c h ro n i c i nflammation) as wel l as chemicals (beta
nap hthylam i n e , benz i d i ne) play a rol e .
Gross Findings. S i m i lar t o ben i gn pap i l lomas, pap i l lary carcinomas appear a s v i l l o u s
structu res w i t h b ranc h i n g excrescenses o n a sta l k . I n i t s m o re advanced stages the
t u m o r appears as a cau l i flower- l i ke fi rm mass which i nfiltrates the adjacent b ladder
wal l .
Microscopic Findings. The t u m o r co n s i sts o f papi l lary growths which have a con nec
tive tissue sta l k covered by i rregu larly-th i ckened transitional cel l epithel i u m
( u rothel i u m) , wh ich n u m be rs a t l east eight t o ten cel l l ayers. The stratification o f the
u rothel i u m i s i rreg u l a r , the p ro l iferati n g cel ls fo rm c l u sters of d i sorgan ized cel l s .
T h e epithelial b u d s often do not have a con n ective tissue co re . T h e shape a n d size
of the t u m o r cel l s is variabl e ; they are polygo n a l , have l arge oval hyperchromatic
n u cle i . Abu ndant m itoses, among them abnormal m itotic f i g u res, can be observed.
The epithel i u m i s not s harply demarcated from the con n ective tissue. The p ro l i ferat
i n g t u m o r cel l s have b roken t h ro u g h the basement mem b rane and have i nvaded the
stroma. At the base of the sta l k the t u m o r cel l s i nfiltrate the bladder wal l , for m i n g
i rreg u l a r nests and cel l gro u p s . Papi l lary tran sitional cel l carci nomas of t h e bladder
are graded i nto th ree gro u ps accordi n g to the degree of h istologic and cytologic
abnormalities. The criteria for g rad i ng are based o n th ickness and d i sorgan ization of
the epithel i u m , atypi a of tumor cel l s , n u mber of m i toses and i nfi ltrative growth .

Fig. 102A. K

su pportive con nective tissue; H epithel ial buds;

F wall of u r i n a ry bladder.
Fig. 1028. T t u mor cells with atypia; M m i toses.

218

1 0 3 . Seminoma
H e m atoxyl i n -eos i n

S e m i n oma i s a mal ignant t u m o r that ari ses from germ cel l s . The tumor i s very
rarely seen before p u be rty, it occu rs most often i n you n g ad u lts and midd le-aged
men .
Gross Findings. The size of the t u m o r varies between 0 . 5 to 1 0 cm i n d i amete r. Cut
s u rface s hows a l o b u l ated, b u l g i n g , tan to wh ite soft mass. Larger tumors freq u ently
have gray to yel low areas of necrosis and p u rp l e foci of hemo rrhage.
Microscopic Findings. S e m i'nomas characte ristically have large, ro u n d o r polyhedral
cel l s loosely arranged in sheets and cords. The t u m o r cel l s resem b l e spermatocytes
and are fai rly u n i fo r m . Their n u clei are large, rou n d , vesicular and have a fine
c h romati n network with one o r two conspicuous, dark n ucleo l i . M itoses are in
freq uent. The tumor cel ls have a fi nely foamy cytoplasm which conta i n s m i n ute vac
u o l e s . Best's carm i n e sta i n for glycogen reveals b ri ght red i ntracytoplasmic gran u les
at the s ite of the vacuoles. G lycogen has been d issolved d u ri n g fixation of the tissue.
The n ests of tumor cel l s are enclosed by th i n wal l s of stroma, from which delicate
septa of co n n ective tissue s u bd i v i de the tumor i nto s m a l l e r o r larger lobules. The
stroma i s vascu lar and shows a characteristic lymphocytic i nf i ltrate, p resu mably as
an i m m u n e response of t he host to the tu mor. An abu ndant lymp hocytic i nfi lt rate is
generally s u ggestive of a m o re favo rab l e p rognosi s . Someti mes the sem i noma is
accompan i ed by an e m b ryonal carcinoma, wh ich i n d icates a poor prognosis.

220

Fig. 103. T

tumor c e l l s ; 5

stroma; L y - lymphocytic i nfiltrate.

Ly

1 04. Embryonal carci noma of testis

(CA RCI N O MA E M B RYONALE TEST I S)
H e m atoxyl i n -eos i n
This i s a h ig h ly mal ignant t u m o r ; i t comp rises 20 to 25% of pri mary germ cel l
t u m o rs o f the testi s . E m b ryonal , i m matu re cells o f a l l th ree germ cell layers occ u r i n
t h e t u m o r , the refore o n occasion it may b e d i ffi cult t o d raw t h e l i ne between emb
ryonal carci noma a n d i m mat u re te ratom a .
Gross Findings. T h e t u m o r generally i s smal l , 1 .0 to 3 . 0 cm i n diameter; exception
a l ly e m b ryonal carc i n o mas are l arge. The tumor i s mostly firm, gray-wh ite and its cut
s u rface i s often mottled, showi n g yel low areas of n ecrosis and foci of hemo rrhage .
Microscopic Findings. I m mat u re epith e l i al cel l s with embryo nal featu res are seen
in a l oose, myxo i d stroma wh ich may conta i n u n d i fferentiated s p i n d l e cel l s . The
arrangement of the t u m o r cel l s i s variab l e ; some gland- l i ke or tubular structu res
with pap i l l a ry p rojections of prol iferat i n g cel l s are occasionally see n . I n l ess d i fferen
tiated t u m o rs the cel l s fo rm i r regu lar i s lands and b u n d les. The u nd i fferentiated
t u m o r cel l s vary greatly i n size and ti ncto rial characte ristics . I n genera l , the n u clei
are hyperc h romatic, although thei r c h ro mati n content varies. The dark n u cleo l i are
co n s p i c u o u s ; the cel l s have a t h i n r i m of cytoplasm and the i r borders a re i n d i stinct.
Mitoses are freq uent and bizarre m u lt i n ucleated giant cel l s are not rare. In contrast
to semi nomas, the t h i n fascicles of stroma are n ot i nfiltrated by Iymphocytes.

222

Fig. 104. T - nests of tu mor cel l s ; L u - l u me n ; 5 - stroma; L - i nflam matory i n filtrate.

1 0 5 . Adenocarci noma of prostate

(CA RCI N OMA PROSTATAE )
H e m atoxyl i n -eo s i n
Carcinoma o f the p rostate i s one of the most freq uent tumors, primarily occu rring
in m e n ove r 50. Among p redisposing factors some en docri ne d i stu rbance seems to
be most l i kely.
Gross Findings. The cut s u rface of the prostate i s very f i r m , d ry and u n iformly tan .
Microscopic Findin,gs. The pict u re is that of an adenocarcinoma. Most freq uent are
well-differentiated adenocarc i nomas, in which the t u m o r cel ls form med i u m-size or
s m a l l e r glands. These t u m o rs deceptively resemble n o rmal prostatic glands. Recog
n ition of the t u m o r is aided by the fact that the n ewly formed neoplastic glands are
gen e ra l l y s m a l l e r and n u merous, often tightly packed back to back, not separated
from each othe r by con n ective tissue. I n many i n stances no basement membrane
separates the glands from the stroma. I n poorly differentiated adenoca rcinomas
there may be sol i d ce l l nests without a gland u lar l u m e n or j u st smaller nests and
cords of t u m o r cel l s in a dense, f i b ro u s stroma. These l ess d i ffe rentiated tumor cel l s
are of s i m i lar size a n d shape, cuboidal o r polyhedra l . The i r n u clei are centrally lo
cated, smal l , sphe rical and hyperc h romatic. The n u cleo l i are promi nent, m itotic fi
g u res are rare . The t u m o r cel l s have a sparse, pale cytop lasm i n which, s i m i lar to
ben i gn p rostate glands, acid phosphatase activity can be demonstrated. There is a
good correlation between the h isto logic appearance and cl i n ical behavior of the
t u m o r . Adenocarci n omas of the p rostate are graded accord i n g to the size and confi
g u ratio n of the neop lastic glands they form , as wel l as by the level of cytologic
atypi a . Based on these criteria adenoca rc i n omas are class ified as wel l -d ifferentiated ,
moderately d i fferentiated or poorly d i fferentiated .

Fig. 105A. M n o n - n eoplastic glands; T tumor.

l u m en in moderately d ifferenti ated adenocarci noma;
C compact nests of t u m o r cel l s ; 5 stroma.
-

224

Fig. 1058. L

1 06. Pregnancy
(G RAV I D I TAS)
H e m atoxyl i n -eo s i n
D u r i n g the m en strual cycle the endometri u m i s i n a state of special preparation
for the reception of the fert i l ized egg. After i m pl antation f u rther changes s u pport
the n utrition and p rotection of the grow i n g e m b ryo . If the fal lopian tube i s narrowed
or obstructed by chron i c i nflammation or scarring, the fe rt i l ized ovu m can not reach
the uteri n e cavity. I n such i n stances the e m b ryo wi l l attach and grow o utside the
ute r u s , most often in the fal lopian tube (tu bal p regnancy) . I n such a case the ex
trauterine p regnancy may l ead to tubal r u pt u re and l i fe-th reate n i n g hemo rrhage .
Microscopic Findings. The age of early gestation can be estab l i s hed by the charac
teri stics of the endometri u m . I n the first month of p regnancy the endometri u m be
comes the decid ua, in which a m o re s u perficial compact layer with narrower glands
and a deeper spongy layer with e n larged and saccu l ated endometrial glands is noted.
The glan d u lar epithel i u m i s vacu o l ated , i n d icat i n g i ncreased secretory activity. The
stromal cel l s of the decidua are en larged , polyhed ral , tightly packed resem b l i n g a
pavement. The decid ual cel l s have spherical n u clei and ample fai ntly eosi noph i l ic
cytop lasm which i s rich i n glycoge n . The stroma is vascular and n u m erou s d i lated
b lood vessels can be see n . Afte r the second month of p regnancy the glands grad u a l ly
d i sappear and by the end of the third month the placenta has developed . At this
stage chorionic vi l l i are p resent which have a loose stroma and are rich in cap i l laries.
The chorionic v i l l i are covered by two cel l laye rs. Basally i s a row of cuboidal Lan
ghans cells, and on the s u rface are the m u lt i n u c leated giant cel l s (syncytial cells)
which have a b rightly eos i n o p h i l i c cytoplasm. The chori o n i c vi l l i a re bathed i n a sea
of maternal e ryth rocytes.
I n tubal p regnancy the fal lopian tube is d i stended , its t h i n wal l s a re stretched and
its l u men is f i l led with b lood and chorionic vi l l i .

Fig. 106. Top : C h - chorionic vil l i ; V blood ; D - decidua.

Fig. 106. Botto m : M - fetal t i ss u e ; N y - m u cosal fragment from su rro u n d i n g fa llopian tube.
-

226

Ny

1 0 7. Hydatidiform mole
(MOlA H YDAT I DOSA)
H e m atoxyl i n -eo s i n
The hydatid iform mole is characterized by edemato u s , ves i c u l a r chorionic vi l l i .
The fetu s d ies i n early p regnancy and the abno rmal vi l l i grow faster than a normal
p regnancy, thus rapi d ly en larg i n g the ute r u s . This p rocess i s accom panied by a pro
l iferative trophoblast from w h i c h , in a small percentage of cases, cho riocarci noma
may arise.
Gross Findings. The uterine cavity conta i n s characte ristic grape- l i ke cystic struc
t u res which range from a few mm to as large as 3.0 cm in diameter.
Microscopic Findings. The key features are marked stromal edema of vi l l i and
trophoblastic p ro l i fe ratio n . The chorionic vi l l i are markedly e n l a rged and swo l l e n ,
the i r stroma is extraord i na r i ly l oose, d u e t o edema a n d central l i q uefactio n . I n the
v i l l i the b lood vessels are ten u ou s , do not conta i n blood; many vi l l i are avascular.
There i s a c i rcu mferential proliferation of trophoblast o n the s u rface of the vi l l i . I n
the p ro l i fe rat i n g cel l popu lation the cuboidal cytotrophoblast and m u lt i n u cleated
syncytiotrophoblast can be see n . The trophoblast is i rregu larly p ro l iferati ng, some
times fo r m i n g buds or cel l col u m n s without s u pportive co n nective tissue. Due to
the rapid swe l l i ng of the stroma d egen e rative changes (vac u o l ization) can be seen
in the trophob last. On the giant v i l l i the trophoblast i s atten u ated and may be foca l ly
n ecroti c. Based on morphologic and cytogenetic evidence many consider a
hydati d iform mole to be a true neoplasm s i nce the shape, size and ti ncto rial charac
teristics of the trophoblast are q u ite variable and DNA ploidy analysis reveals its
a n e u p l o idy.

228

Fig. 107. 5

edemato u s stro m a ; C h - chori o n i c epithel i u m (pro l i ferat i n g trophoblast) ;

B - b u d of trophoblast cel l s .

1 08. Erosion and pseudoerosion of uterine cervix

(EROSI O VERA ET PSEUDOEROSI O PORTI O N IS VAG I NALlS UTERI)
H e m atoxyl i n -eo s i n
E rosion is a d e n ud ation of the s u perficial epithelial layers. A true erosion (erosio
vera) of the cervix i s very rare . I t may lead to precancerou s changes. A pseudoero
sion of the cervix i s seen when the col u m nar endocervical epithel i u m m igrates
downward and replaces the squamous epithel i u m of the exocervix. This usually is
the res u l t of l aceration and is considered to be a "tu r n i n g out" (ectropion, eversion)
of the edematou s vascular endocervix.
Gross Findings. Both co nditions s how a s i m i l a r pictu re . With the naked eye o r with
the col poscope velvety red patches are seen i n a ring a ro u n d the exte rnal cervical
os. Sch i l ler's i o d i n e test is n egative in the area of e rosion or pseudoe ros i o n , whereas
the adjacent glycogen-rich stratifi ed squamous epithel i u m sta i n s mahogany b rown .
Microscopic Findings. I n true erosion the stratified squamous epithel i u m is not pre
sent. The d e n uded s u rface of the exocervix is covered by eosi noph i l ic fibrin and
amorphous cel l u lar debris. The base of the s u pe rficial u l cer i s i nfi ltrated by ro u n d
cel l s . An i ncrease i n f i b ro blasts and con n ective t i s s u e fi bers, as wel l as p ro l i ferating
capi l l aries can be seen . A pseudoerosion may show th ree h i stologic types. In a simple
pseudoerosion a s i ngle row of col u m n a r epithel i u m g rows from the endocervix over
the d e n u ded exocervix. The cytoplasm of the col u m na r cel l s is of a secretory type,
it sta i n s l i ghtly and is finely foamy. I n a glandular pseudoerosion u nder the col u m nar
epithel i u m there are also cervical glands. The t h i rd type, papillary pseudoerosion, is
characerized by papil lary growths which rise above the s u rface of the cervix. These
papi l la ry structu res are covered by a single row of endocervical type col u mnar
epithel i u m . A l l th ree types of pseudoerosion have an edemato u s , loose stroma with
a ro u n d cel l i nfi ltrate .

Fig. 1OBA . True erosi o n .

i nflammatory i n f i ltrate; V blood vessels;
C en docervical glands.
Fig. 10B8. S i mple pseudoerosion .
L squamous epithel i u m ; C endocervical type mucosa.
Fig. 10BC. G l a n d u l a r pseudoerosion.
en docervical glands; N
muci n-prod ucing col u m n a r epithe l i u m .

squamous epithel i u m ; E

eros i o n ; I

230

1 09. Squamous cell carcinoma of uterine cervix

(CARCI N OMA PO RTI O N I S UTERI )
H e m atoxyl i n -eos i n
Carcinoma of the uterine cervix i s usually seen i n women over the age of 40 years. Since
the cervix is easily accessible to exami nation , precancerous conditions and intraepithelial
neoplasia (carcinoma-in-situ) can be also recognized. In the early diagnosis of these condi
tions gynecologic cytologic examination (Papanicolaou smear) is of great help.
Gross Findings. Early cervical cancer is simi lar to cervical erosion, but the ulcer base is less
fi rm, soft, friable and does not resist the examining probe. Advanced cervical cancer may
g row predominantly exophytically or endophytically. Exophytic carcinoma is a cauliflower
n ke lesion, which is friable, easil y bleedin g , gray to purple with yellow areas of necrosis.
Endophytic carcinoma enlarges t h e cervix b y growi ng into it and the ulcerated cervix be
comes a funnel-shaped crater.
Microscopic Findings. The World Health Organization (W. H.O.) has termed cervical
cancer precu rsors as c e r v i c a I i n t r a e p i t h e I i a I n e 0 p I a s i a (ClN) characterized by
atypical cells with hyperchromatic nuclei in the squamous epithelium. Depending on the
extent of cel lu lar pro l iferation, matu ration and cytological atypia, ClN may show mild (ClN
1), moderate (CIN 2) or severe dysplasia/carci noma i n situ (CIN 3). There are th ree histologic
types of a d v a n c e d c e r v i c a I c a r c i n 0 m a, although they can also occur combined.
Cells of keratinizing squamous cell carcinomas retain their squamous appearance, but are of
variable size and shape. The n uclei are round or oval, varying in size and staining, occasion
all y showing regu lar and abnormal mitotic figu res. The cytoplasm of some im mature tumor
ce l ls contains brightly eosinophilic keratinaceous material (dyskeratosis). The tumor cells
are not regu larly stratified, but form cell nests of varyi ng size and shape. These nests are
confluent In some areas and without distinct borders, dee p ly invading the connective tis
sue. In the center of some cell nests there are concentric l amellar eosinophilic structures
called keratin pearls. The stroma of the tumor is i nfi ltrated by round cells. In non-keratinizing
large cell carcinomas the tumor cells are similar to those of the prickle cells of stratified
squamous epithelium. Evidence of keratinization is rarely noted. The tumor cells form smal
ler-larger nests, are rather pleomorphic and vary in size. The cell n uclei are round or oval
and hyperchromatic. Mitoses are frequent. The tumor cells have ample, eosinoph i l ic cytop
lasm. Small cell carcinomas are characterized by somewhat elongate, spindle-shaped ce l ls
resembling basal cells of the squamous epithelium. The tumor is composed of sheets and
cords of tightly packed small cells that diffusely infi ltrate the stroma. Sometimes only the
nesting pattern distinguishes these tumors from sarcomas.

232

Fig. 109A . Carcinoma-i n-situ .

H - intact squamous epithel i u m ; C - carcinoma; Ly - lymphocytic i nfi ltrate; K - co n nective tissue.
Fig. 109B. I nvasive squamous cell ca rcinoma.
H - i n tact squamous epithel i u m ; U - u l ceration ; Ly - lymp hocytic i nfi ltrate; K conn ective tissue.
-

1 1 0. Serous and mucinous cystadenomas of ovary

(CYSTOMA SE ROSU M ET M U C I N OSUM OVARI I )
H e m atoxyl i n -eo s i n
Cystade no mas are cystic t u m o rs which arise from the coelomic (su rface of body
cavity) l i n i n g , not from germ cel l s . Cystadenomas occ u r in ad u l t females. The serous
t u m o rs tend to be bi lateral , the m uc i n o u s t u m o rs are u s u a l ly u n i latera l . Mal ignant
fo rms of the t u m o rs (cystadenocarci noma) are seen i n elderly wome n .
Gross Findings. Cystadenomas have a smooth s u rface a n d may b e anywhere from
2 to 20 cm in d iamete r. The t u m o rs may be u n i locular o r m u ltilocular; the i nd ividual
locu l es vary in size. The cyst wal l s are rubbery, thick o r t h i n , transl ucent membranes.
Serous cystadenomas have a s moot h , s h i n y l i n i n g . O n the cyst wal l there may be s l i m ,
p l iable excrescences o r ped u n c u lated cau l i flower- l i ke , b road-based growths. The
l u men i s fi l l ed with straw-colo red sero u s f l u i d . Mucinous cystadenomas have smooth
wal l s , excrescences are very rare . The cavities are f i l led with viscou s , gelati nous,
transparent material . I f the cysts rupt u re , islands of m u cu s-secreting epithel i u m may
i m p lant on the perito n e u m and gelati n o u s mate rial wi l l spread throughout the
peritoneal cavity (pseudomyxoma peritonei).
Microscopic Findings. Com partm ents of varyi n g sizes and shapes are see n . The wal l
o f these cystic spaces co n s i sts o f t h i n septa o f f i b ro u s co n n ective tissue l i ned by
epithel i u m . I n serous cystadenomas pap i l lary growths may p rotrude i nto the l u me n ;
these struct u res have a core o f co n n ective tissue which forms a t h i n sta l k a n d s u p
ports its b ranches . The cysts and the pap i l lary growths are l i ned by a s i ngle row of
c u boidal or col u m nar epithel i u m which someti mes is c i l iated , resem b l i ng tubal
epithe l i u m . Rou n d , concentrically lami nated cal cified gra n u les, psammoma bod ies,
are freq u ently seen in the stroma. The cysts of mucinous cystadenomas are l i ned by
a single laye r of regu lar col u m nar cel l s resem b l i n g those of the en docervical glands.
The n u clei are basa l l y l ocated , the vacuolated cytop l asm i s f i l led with m uc i n and
stai n s s l i ghtly b l u e . Large r cysts are l i n ed by flattened, cuboidal epithe l i u m , or may
be d e n u d e d . I n malignant variants of these t u m o rs the l i n i ng epith e l i u m p ro l i ferates,
forms pap i l lary growths without a co n n ective tissue core. The malignant epithel i u m
shows i rregu lar stratificat i o n , pleomorp h i sm a n d m itoses .

Fig. 1 1OA . Serous cystade noma.

papi l l ary growth ; H - col u m nar epithe l i u m .
Fig. 1 108. M u c i n o u s cystadenoma.
C - cyst space ; S - stroma; H - m u c u s-secret i n g col u m na r epithel i u m .
C

234

cyst space ; P

H
s

1 1 1 . G ranulosa-theca cell tumor of ovary

(TUMOR GRA N ULOSOCELLULARE ET TH ECOCELLU LARE OVARI I )
H e m atoxyl i n -eo s i n
These t u m o rs origi nate from the sex co rd stroma and may secrete hormones . Most
often they p roduce estrogens, therefore i n gi rls they lead to p recocious sexual de
velopment and i n ad u lt women to i rregu lar, excessive uteri ne b leed i n g or post
menopausal bleed i n g , respectively. F i b rocystic changes of the b reasts, carci noma of
the b reast and endo metri u m have also been associated with the m . P u re theca cel l
t u m o rs generally are ben i g n , p u re g ran u l osa cel l t u m o rs o r m ixed, gran u losa-theca
cel l t u m o rs have a low to moderate mal i gnant potential.
Gross Findings. Sex co rd-stromal t u m o rs are u s u a l ly u n i latera l , and 2 to 20 cm in
l argest d i a m eter. Granulosa cell tumors have a yel low to tan cut s u rface, with in
terspe rsed small er-larger cysts . Thecomas (also cal led fibrothecomas) have a nodu lar
s u rface and are b right yel low to och re. They have a firm, lobu lated cut s u rface with
gray-white septa d e l i n eat i n g the l o b u l e s .
Microscopic Findings. Granulosa cell tumors have cuboidal o r polygonal cel l s with
oval and pale n uclei . The t u m o r cel l s fo rm small i slands, b ranc h i n g trabecu lae or
gland- l i ke structu res in a sparsely f i b ro u s stroma. Cysts l i ned by m u ltiple layers of
gra n u losa cel l s can someti mes be observed . The Call-Exner bodies are d i stinctive
configu rations which s i m u late the arrangement of gra n u losa cel l s in the G raafian
fo l l icle. The Call-Exner bodies are m i c roscopic cavities which contain p reci pitated
eos i noph i l ic f l u i d and are s u rro u n ded by a rosette of t u m o r cel ls . Thecomas h i stolog
ica l l y resemble f i b romas. The thecoma ce l l s are s p i n d le-shaped and have elongate
n u clei . The i r cytoplasm conta i n s b i refri ngent l i pids, i n c l u d i n g i m m u noh i stochemi
cal ly demo nstrable steroi d hormones. The thecoma cel l s are arranged i n i ntersecting
b u n d les, strands and occas ional whorls. The stroma i s sparsely cel l u lar and co nsi sts
of thick, hyal i n ized col lagen b u nd l es separat i n g the smal ler or larger cell groups.

236

Fig. 1 1 1A . G ra n u losa cel l tumor.

G - gra n u l osa cells; 5 - stroma; V - blood vesse l ; C - Cal l -Exner body.
Fig. 1 1 18. Thecoma.
T - elongate t u m o r cells; 0 whorl - l i ke arrangement of tumor cel l s .
-

1 1 2. Fibrocystic disease of breast

(MASTOPATH lA FI BROCYSTI CA)
H e m atoxyl i n -eo s i n
F i b rocystic changes are com m o n i n the b reasts of m i d d le-aged , p remenopausal
wom e n . Pres u mably hormonal i m balance may play a rol e i n the i n d uction of fib
rocystic changes . Earl i e r these were co nsidered to be a p recancerous condition si nce
10 to 20% of them are associated with b reast cancer. H owever, t h i s association i s not
causal .
Gross Findings. The changes m ay be focal or m u ltifocal , u n i lateral or bilatera l ; 0.5
to 1 .5 cm large, c i rc u m scri bed fi rm struct u res are palpable i n the b reast. O n the cut
s u rface of the b reasts b rown to straw-yel low cysts of vary i n g size can be see n ; these
cysts are f i l led with clear or thick t u rb i d fl u i d .
Microscopic Findings. T h e epithelial component a s wel l a s t h e co n n ective tissue are
i n c reased, the d i stended d ucts appear as cysts of vary i n g sizes . The cysts conta i n
fai ntly eosinoph i l ic p rote i naceo u s p reci pitate. T h e s m a l l e r cysts a re l i ned b y cuboi
dal o r col u m n a r epithel i u m which foca l ly may have proliferated and formed m u ltiple
ce l l layers. Freq u e ntly proliferat i n g papi l lary structu res with a t h i n core of con n ective
tissue fi l l the l u me n s u ch that o n ly a c i rcumferential s l it-l i ke space sepa rates them
from the epithelial l i n i n g of the cyst. The epithe l i u m of the large cysts is flattened or
m ay be com p l etely absent; these cysts are l i ned by tightly arranged paral lel col lagen
fibers . A characte ristic of f i b rocystic changes i s that the cyst l i n i n g often resem bles
the epithel i u m of apocrine sweat glands (apocrine metaplasia). Such cel l s are
rou nded, have abu ndant, f i n ely gran u lar, stro ngly eos i noph i l i c cytoplasm which
contai n s s m a l l sec retory vacuoles n ear the l u m e n . The characteristic loose fi brous
stroma has been rep l aced by den sely packed col l agen fi bers which may appear
h omogeneou sly eos i noph i l ic and hya l i n ized . The f i b ro u s stroma is freq uently i nf i l
trated b y Iymphocytes, p lasma cel l s and macro phages w i t h a foamy cytop lasm . Pre
s u mably t h i s is a reaction to the contents of the cysts which escaped through a
rupt u re i nto the s u r ro u n d i ng tissues.

238

Fig. 1 12. C

cysts; M

apoc ri n e metaplasia; E

gland u lar t i s s u e ; I

fibrous stroma.

1 1 3. Fibroadenoma of breast
( FI BROADEN OMA MAMMAE)
H e m atoxyl i n-eos i n
Fib roadenoma i s the most com mo n ben ign t u m o r of the female b reast and occurs
in you n g women between 20 and 30 years of age . Its pathogenesis i s related to
hormonal alterations.
Gross Findings. The t u m o r is 0.4 to 3 .0 cm i n d i ameter, f i r m , encaps u l ated , sharply
demarcated and freely movab l e i n the b reast . On cut s u rface the tumor is bu lging,
pearl-wh ite and has a whorled appearance with tiny tan to yel low foci .
Microscopic Findings. S i m u ltaneous prolife ration of connective tissue and glandu
lar epithelium is seen i n the t u m o r . The gro u n d s u bstance consists of loose fibrous
tissue with s p i n d l e-s haped f i b roblasts. With i n this con n ective tissue there are gro u ps
of d ucts of variable shape and l ength . These d ucts are l i ned by a s i ngle or double
row of regu lar cuboidal o r polygonal cel l s which have spherical n uclei ; no mitotic
activity i s see n . A wel l-deve loped basement m e m b rane separates the epithel i u m
from t h e f i b ro u s stro m a . Some d ucts have a ro u n d o r oval l u men s u rrou nded by
concentrically arrange d , densely packed col lagen fibers (pericanalicular fibroadeno
maY. I n other i n stances the p ro l iferati n g stroma b u l ges i nto the d u ct, p u s h i n g its
epithelial l i n i n g i nto the l u me n . T h i s way the l u men becomes d i storted , s l it-l i ke,
sickle o r star-shaped . Some l u m i na co m p l etely d i sappear and are i nd i cated o n ly by
two closely apposed rows of epithel ial cel ls (intracanalicular fibroadenoma). Both his
tologic types of f i b roadenoma may be p resent i n vario u s p roportions wit h i n one
tumor.

Fig. 1 13A. Pericanalicular fibroadenoma.

d u ctal l u me n ; K concentric con n ective tissue fibers.
Fig. 1 138. I ntracanalicular fibroadenoma.
L - slit - l i ke l u me n ; K - c u s h i o n - l i ke protrusion of co nnective tissue.
L

240

1 1 4. Paget's disease of nipple

( CARCIN O MA MAMILLAE PAC ET)
H e m atoxyl i n -eo s i n
Paget's d i sease o f the n i pp l e i s a special fo rm o f d u ctal carci noma arising from the
lactiferou s d u cts. The t u m o r m ay a l so exten d to the epidermis of the areol a . Earl ier
the changes of the n i pple were thought to be i nflammatory. In fact, the s u perficial
lesion of the n i pple i s due to i ntraep idermal sp read of an u nderlying carci noma.
Gross Findings. The n i pp l e may be defo rmed . There i s redd e n i n g and ooz i n g at its
s u rface s i m i lar to skin changes of eczema. In more advanced cases there are fiss u res
and u lcerat i o n , the p rocess extends to the a reola a n d , later, to the adjacent s k i n of
the b reast .
Microscopic Findings. The kerati n iz i n g stratifi ed squamous epithe l i u m of the n i pple
i s i nfi ltrated by characte ristic large, rou n d o r polygonal cel l s , the Paget's cel l s . These
cel l s have abu n dant pale, sometimes f i nely foamy cytoplasm with a peri n uclear clear
halo. The n u cleus is l a rge, ro u n d o r oval, dark, and has a p ro m i nent n u cleo l u s .
Occasi o n al m itotic Paget's cel l s c a n b e observed. The appearance o f Paget's cel l s i s
s i m i l a r to that of the carc i n o m a i n t h e l acti fe ro u s d u cts . H i stochemical and electron
m i croscopic studies have shown that the i nt raepi de rmal Paget's cells origi nate from
the epithel i u m of the l actiferou s d u cts . Immunohistochemically casei n cou l d be
fou n d i n the cytoplasm of Paget's cel ls , a prote i n characte ristic of m i l k . I n advanced
cases the epidermis i n f i ltrated by t u m o r ce l l s i s n ot sharply d e l i n eated from the
derm i s which shows a dense i nflammato ry react i o n .

242

Fig. 1 14. L

epidermis o f n i pple (kerati n iz i n g stratified squamous epithel i u m ) ;

P - Paget's cel l s ; I
i nflam matory i nfiltrate.
-

1 1 5 . Paget's disease of bone

H e m atoxyl i n -eo s i n

The d i sease occ u rs primarily i n older men ; its eti o logy i s u n ce rtai n . The changes
may affect a s i ngle bone (monostotic form) or may i nvolve several bones {polyostotic
form}. Osteosarcoma develops i n about 1 -2 % of widespread Paget's d i sease .
Gross Findings. The affected bones are stri ki ngly thickened; they are bent, de
formed and the i r s u rface i s rou g h , u neven . The bones are soft, sometimes they can
be cut with a k n ife . On cut s u rface the marrow cavity is narrowed , the bone marrow
is f i b ro u s , fi rm ; it s h ows red to b rown patches and small cavities of variable size.
Microscopic Findings. Paget's d i sease of bone i s characerized by ab normal bone
formation o n and off at i rreg u l a r i nterva l s . I n the active phase of the d i sease both
osteoclasts and osteoblasts show an i n c reased activity, i . e . i ntensive reso rption of
bone is associated with new bone format i o n . Osteoclasts are m u lt i n u cl eated large
cel l s with a m p l e acidop h i l ic cytoplas m and up to 1 00 n uclei . Osteoclasts break down
the bone i n deep grooves ( H owshi p's lac u n ae) on the trabec u l a r s u rface, and i n
newly fo rmed perforat i n g canal s . Osteoblasts l i ne the s u rface o f cortical and
trabecu l a r bone, they are oval o r elo ngate monon uclear cel l s . The cytoplasm of the
osteoblasts is i ntensely basoph i l i c and has a perin uclear clear zone (fo rmed by the
Golgi apparatus) . Osteoblasts p roduce osteoi d ( n o n - m i neral ized gro u nd s u bstance
of bone) which is deposited on the s u rface of the bone and adds to the th ickness of
the bone trabecu lae . I n Paget's d isease the lamellar bone shows a characteristic,
mosaic patte rn . The trabecu l ae are abnormally thick and com posed of chaoti cal ly
j u xtaposed , i rregu l a rly-shaped p i eces of lamellar bone demarcated by i rregular
cement l i ne s . The i ntert rabecu lar spaces a re f i l led with vascu lar, loose fi brou s con
nective tissue. The i nvolved bones b reak eas i ly becau se their hap hazard architecture
i s n ot capable of adeq uately f u l fi l l i n g the physical req u i rements.

244

Fig. 1 15. O b - osteoblasts; L - lamellar bone; M - mosaic pattern of bone;

Z - cement l i n e s ; O k - osteoclast.

1 1 6. Chondroma
H e m atoxy l i n -eos i n

A c h o n d roma i s a benign tumor a ri s i n g i n cart i l agi neous tissue. I ts typical sites of

o r i g i n are the bones of the hands and feet, the long bones of the extrem ities and
the r i b s . They can occ u r rarely in soft tissues wh ich normally do not conta i n cart i l age
( e . g. synovia) .
Gross Findings. C h o n d romas are e ncaps u l ated t u m o rs which have a nodular s u r
face a n d appear l o b u late d . They a re f i rm a n d can be cut with a kn ife ; their cut
s u rface is glassy, tra n s l u cent and gray to b l u e .
Microscopic Findings. T h e t u m o r con s i sts o f hya l i n e carti l age- l i ke tissue which
fo rms lobu les of varyi n g s izes separated by septa of loose fibrous tissue. The cart i l
age cel l s a re i rreg u l arly scattered and em bedded i n the homogeneous, fai ntly
basoph i l i c matu re cart i laginous matrix. The t u m o r cel l s are spherica l , moderately
vary i n shape and size; the n u clei are freq uently deep b l u e . M itotic figu res are sel
dom see n . Some t u m o r cel l s sit with i n l ac u n ae , however, n ot in pairs as i n non
n eo p lastic carti lage, but s i ngly. O utside the lac u n ae the tumor cel l s are lying i n the
matrix si ngly or in small c l u sters. The islands of carti lage are s u rro u n ded by con nec
tive tissue which is rich i n f i b rob lasts and blends with the carti lagenous matri x .
C h o n d romas freq uently show dark basoph i l i c areas of cal cification and a l s o ossifica
tio n . I n vol u m i no u s l a rge t u m o rs there may be evi dence of regressive changes, fo r
i n stance cyst formation or myxo i d ( m ucoid) degeneratio n .

246

Fig. 1 16. M

carti lagenous matrix; 5

t u mor chond rocytes.

1 1 7. Osteosarcoma
H e m atoxyl i n -eo s i n

Osteosarcoma i s the most frequent p r i mary mal i gnant t u m o r o f bone. I t arises

from u n d i fferentiated i ntraosseous or periosteal mesenchymal cel l s that mod u late
i nto mal ignant osteob lasts , capabl e of p rod u c i n g osteoid as wel l as tumor bone.
Osteosarcomas most com m o n ly occ u r in ch i l d re n and yo u n g ad u lts, and affect males
m o re often than females . The t u m o r i s most com mo n l y fo u n d i n long bones (fem u r ,
t i b i a, h u me r u s ) .
Gross Findings. The t u m o r ari ses i n the metaphyseal area, it breaks t h rough cortical
bone and i n f i ltrates adjacent soft tissues. On cut s u rface the tumor appears soft,
fish-flesh o r p i n k , with areas of hemorrhage and necro s i s as wel l as more differen
tiated tissue with m uc i n o u s , cart i l ag i n o u s or osseous portio n s .
Microscopic Findings. Osteosarcomas c a n be d i fferentiated o r dedifferentiated . I n
differentiated t u m o rs osteoblast- l i ke i m matu re mesenchymal cel l s are p ro l i ferati ng.
These t u m o r cel l s a re elongate o r polygo n a l , thei r n u clei are ova l , hyperchromatic,
of d i ffe rent shape and size. M u l t i n u cl eated t u m o r giant cel l s and atypical m u ltipolar
m i toses can be freq uently observed . The pleomorphic tumor cel l s p rod uce d ifferent
gro u n d s u bstances . Abno rmal osteoid p roduction by atypical osteoblast- l i ke cel l s i s
characte ri stic. These t u m o r cel l s a r e n o t a l i g n e d along t h e s u rface of t h e osteo i d ,
but a r e scattered with i n the i nterstices o f a l attice- l i ke eos i noph i l ic osteoi d matrix.
The malignant m esenchymal cel l s may also p rod u ce a m i ne ralized matrix, tumor
bone. T h i s appears as small bone spicu l es i n the vascu lar f i b ro u s stroma d i sti nctly
d i fferent from the normal trabecu lae of lamellar bone. I s lands of cartilaginous
gro u n d s u b stance can also be seen, i n which the atypical (malignant) cartil age cel l s
sit i n i r regular lacunae. I n oth e r areas the gro u n d s u bstance i s myxoma-like with
starshaped atypical ( m a l ignant) cel l s in the loose, m u co i d stroma. I n dedifferentiated
osteosarcomas the cel l u lar t u m o r is composed of bizarre mesenchymal cel l s of vari
able s ize (neoplastic osteoblasts) . The gro u n d s u bstance p roduced by the tumor
cel l s i n not p ro m i n ent. The stroma co n s i sts of loose fibro u s tissue which contai ns
d i lated bl ood vessels. The h i stologic d i agnosis of ded iffe rentiated osteosarcomas i s
a i d e d b y the h i stochemical demonstration of al kal i ne p hosphatase activity i n the
t u m o r cel l s . With this method the osteogen i c n at u re of the t u m o r can be ve rified
even in cases where the f i b ro u s , myxoi d or carti laginous matrix i s domi nant.

248

Fig. 1 17A. T

tumor cel l s ; 0 osteoid spicules; F fibrous stroma.

Fig. 1 178. T tumor cel l s ; P chondro i d matrix.
-

1 1 8. Nodular goiter
(ST R U MA N O DOSA COLLOI DES)
H e m atoxyl i n -eos i n
E n l a rgement of the thyroi d gland, fo r whatever reason, i s cal l ed a goite r. A goiter
may be n od u lar of d iffu se. The so-cal l ed co l lo i d goiter may be endemic (due to
iod i n e deficiency) or sporad ic, when the defect of one enzyme b l ocks hormone
synthesis. In either case, there i s an i n c reased p roduction of thyrotropin (thyroid
sti m u lati n g hormone, TS H ) d u e to negative feedback, cau s i n g hype rplasia of the
glan d u l a r parenchyma without effective thyroi d hormone p roduct i o n .
Gross Findings. T h e thyro i d gland shows d iffuse o r nod u la r e n largement. The
nod u l es are separated from each other by septa of co n nective tissue. The thyroid
gland i s f i rm and has a tan to b rown gelat i n o u s cut s u rface which sometimes is
mottled with f l u i d-fi l l ed cysts and b rown-red foci of hemo rrhage.
Microscopic Findings. Fol l icles (ac i n i ) of vary i n g sizes, but mostly greatly e n larged
ones, are see n . The aci n i are l i n ed by a s i ngle l ayer of flattened cuboidal epithelial
cel l s . N o cytologic atypi a i s see n . The l u men of the fo l l icles i s f i l l ed with a
homogeneo u s fai ntly eosi noph i l ic s u bstance (co l l o i d ) . The aci n i are separated by
t h i n septa of con nective tissue. Evidence of degenerative changes, such as recent
and o l d hemorrhage, hya l i n ized con n ective tissue or basoph i l ic foci of calcification
can be sporadically obse rved .

250

Fig. 1 18A . H - epithel ial l i n i ng of aci n i ; C - co l l o i d ; K - septa of connective tissue.

Fig. 1 188. C - cysts; V - focal hemorrhage ; Co - colloi d .

1 1 9. Primary thyroid hyperplasia (C raves' disease)

( H YPE RPLASIA DI FFUSA G LA N D U LA E THYREO I DEAE, STRUMA
DI FFUSA BASEDOWIANA)
H e m atoxy l i n-eos i n
The most com m o n cause o f hyperthyro i d i s m i s G raves' d i sease; one of its signs i s
d iffuse en largement of the thyroi d glan d . T h e card i nal symptoms of hyperthyroid ism
are : goiter, tachycard ia and exophthalmos (Merseb u rg triad ) . G raves' d i sease most
often occ u rs in m i d d le-aged women . Pres u mably psychic trau ma and auto i m m u n e
mechan isms play a rol e i n i t s etio logy, s u ggested b y t h e presence o f antithyroid
antibodies in the pati ents' seru m .
Gross Findings. The thyro i d gland i s sym metrical ly, u n iformly e n l a rged and has a
s mooth s u rface. O n cut s u rface the parenchyma is soft, fleshy, pale red to b rown ,
lacks the col l oidal sheen and resembles skeletal m u sc l e .
Microscopic Findings. The m o s t stri k i n g change i s the hyperplas ia of t h e gland u lar
epithel i u m and focal lymphoid aggregates. The aci n i are l i ned by tal l , columnar
epithelium, which has ro u n d , dark n uclei at the base of the cel l s . The p ro l iferat i n g
e p i t h e l i a l cel l s a r e n o t u n iform i n size and s h a p e . T h e colloid i s p a l e , t h i n , depleted
or com p l etely absent. The col loid appears scal lo ped where it abuts the epithel ial
cel l s , considered to i n d i cate hyperf u n ction of the thyroi d gland ( "resorption vac
uoles "). Some acini contain desquamated epithelial cells. S i gn ificant lymphocytic in
filtrate i s observed i n the i nte rlob u l a r septa and the i n terfo l l ic u l a r stroma, form i n g
lymphoid follicles w i t h sometimes p rom i nent ge rminal cente rs . Lymphoid fol l icles
occas ional ly also occ u r in the f i b ro u s stroma of the mou nds or pap i l lary projections
of co l u m nar epithel i u m wh ich p rotrude i nto some aci n i . The hype rplastic gland i s
h ig h ly vascular, n u m ero u s capillaries a r e s e e n i n t h e co n n ective t i s s u e s u rro u n d i ng
the ac i n i .

Fig. 1 19. F glandular fol l i cles; E epithelial m o u n d s ; C co lloid;

scalloped col l o i d ( " resorption vacuoles " ) ; V blood vesse l s ; I
i n terstit i u m .
-

252

R
F

v
c
R

F
E

R
v

1 2 0. Su bacute gran ulomatous thyroiditis of De Quervain

(THYRO I DITIS SU BACUTA G RAN U LOMATOSA DE Q U E RVA I N )
H e m atoxyl i n -os i n
G ran u lo mato u s s u bacute thyroiditis occ u rs m a i n l y i n wo men . It i s thought to be
a viral i n fection or auto i m m u ne d i sease.
Gross Findings. The thyroi d gland is d iffusely, someti mes asym metrical ly e n larged
and may d o u b l e its size. I n advanced cases fi rmer foci are palpable i n the gland : on
cut s u rface these foci appear tan to wh ite i n the othe rwise pale gray and firm paren
chyma.
Microscopic Findings. M u l tifocal changes are seen t h roughout the gland. In the
early stage scattered aci n i with destroyed epithelial l i n i n g can be fou n d . The col loid
from these aci n i h as escaped and i s s u rrou nded by a n i nflammatory reaction of neut
rop h i l s , Iymphocytes, p l asma cel l s . Occasional m i croabscesses have formed i n the
adjacent i nterstiti u m . In advanced stages of the d i sease macrophages aggregate and
multinucleated giant cells of the foreign body type appear. A ring of these i nflammat
o ry cel l s s u rro u n d s the n a ked pools of co l lo i d i n the i n terstiti u m . Presu mably the
escaped col lo i d has been recogn ized as a fo reign s u bstance and has i n d u ced the
gra n u l omato u s reactio n . The h i stologic changes may sometimes resem b le those
seen in t u be rcu l o s i s . In the healing stage there i s f i b rosis which fo l l ows resol ution of
the i nflam mato ry reaction . Often various h i stologic stages of the d i sease may be
seen s i m u ltaneously in a thyro i d gland.

254

Fig. 120. F

- thyroid fol l icles; I - i n terstiti u m ; L - i nflam matory i nfiltrate;

0 - giant ce l l gra n u loma; C central pool of colloid.
-

1 2 1 . Papi llary adenocarci noma of thyroid gland

(CA RCI N O MA PAPILLARE G LANDU LA E THYREOIDEAE)
H e m atoxyl i n -eosi n
Thyroi d cancer occu rs i ll any age grou p , but it is most common i n m id d l e-aged
women . A known carc i n ogenic facto r is i o n iz i n g rad i ation of the neck. Some forms
of thyroi d cancer (fo l l ic u l a r carc i n oma, m ed u l l ary carcinoma) may secrete hor
mones, othe rs do n ot ("co l d " nod u les) .
Gross Findings. I n its early stages the t u m o r is ci rcu mscri bed , more or less encapsu
late d . G rad ually however, it becomes a nod u l e i nfi ltrati n g adjacent tissues, d i stin
g u i s hable by its f i r m , gray-wh ite appearance. I t fi rst metastasizes to the cervical
lym p h nodes, later to bones and l u ngs.
Microscopic Findings. Thyro i d carci nomas may be pap i l lary, fol l icular o r anap lastic.
Med u l lary carci n omas origi nate from the parafo l l ic u l a r o r C cel l s of the thyro i d .
Pap i l l ary carc i n o m as characte ri stica l ly have b ranch i n g pap i l lae s u p po rted by a cen
tral f i b rovascular core ; the pap i l lae are l i n ed by a l ayer of d i fferentiated cuboidal
epithe l ial cel l s . These p ro l i ferati n g epithel ial cel l s show l ittl e atypia and m itotic fi
gu res are exceptiona l . The t u m o r grows i nf i ltratively and i n vades Iymphatics. Con
centrically l a m i n ated , cal cified rou n d structu res (psam moma bod ies) are freq uently
see n ; they are extrace l l u la r and sta i n dark b l u e with hematoxy l i n . Carci noma of the
thyro id i s often wel l d i fferentiated ; in s u ch cases the correct d i agnosis may depend
o n the demonstration of t u m o r i nvasion of the thyro id caps u l e o r b lood vessels.

Fig. 121A . M
normal thyroid gland ; C papi l lary carci noma.
Fig. 1218. A aci n i of tumor; P psammoma body.
-

256

1 22 . Ad renal cortical adenoma

(ADE N O MA CO RTICIS G LA NDULA E SUPRARENALlS)
O i l red 0, h e m atoxyl i n -eos i n
Ad renal co rtical adenoma i s freq u ently a n i ncidental f i n d i n g o n CT scans and at
auto psy; these adenomas often cause no symptom s . Adrenal cortical adenomas may
secrete hormones which, depe n d i n g on the cel l type, p roduce C u s h i ng's syndrome,
v i r i l izat i o n , Conn's syndrome o r ad renogen ital synd rome.
Gross Findings. Adrenal cortical adenomas are 0.3 to 3 . 0 cm i n d iameter, sphe rical
and encapsu lated . The cut s u rface of adenomas is buttery yel low to o range, depend
ing o n thei r l i pi d content.
Microscopic Findings. A thin ccapsu le of con n ective tissue separates adenomas
from the com p ressed ad renal co rtex. The adenoma does not show the zonal layers
of the normal adrenal cortex. The t u m o r cel l s are arranged in i rregularly-shaped
nests, b u n d les, trabecu lae o r somet i mes so l i d gro u ps . The tumor cel l s resemble the
reg u l a r polygo nal cel l s of the n o rmal adrenal cortex. The cytoplasm of some cel l s is
b ri ghtly acidoph i l ic , that of others appears foamy d u e to the i r d i ssolved l i pid con
tent. The i ntracytoplasmic l i p i d sta i n s d eep scarlet red o n frozen sections. The n uclei
of the t u m o r cel l s are rou n d , not hyperch romatic. M i toses are rare. Sometimes the
cel l s s h ow great variation in shape, size and ti ncto rial p roperties; tumor giant cel l s
can a l s o b e see n . These feat u res, however, do n ot s u ggest mal ignancy . The h i s
tologic appearance or l i pi d content of adenomas does not give a c l u e to their endoc
ri ne activity.

258

Fig. 122A. Top : Oil red 0 (frozen secti o n ) .

l i p i d i n ad renal cortical adenoma; T - tumor; K cortex.
Fig. 122B. Botto m : H e matoxyl i n -eos i n .
T - t u m o r cells; K - septu m o f conn ective tissue.
-

1 2 3 . Postvaccinal encephalomyelitis
H e m atoxyl i n -eo s i n

Acute d i ssemi nated e ncep halomyelitis u s u al ly fol l ows v i ral i n fectio n s o r vacci na
tio n . It has been observed as a com p l i cation of measles, chicken pox, rubella or
m u mps, and after s m a l l pox vacci natio n , respectively. Pres umably the vi rus promotes
an auto i m m u n e p rocess which is d i rected agai n st the mye l i n sheath of nerves.
Gross Findings. The re i s a m i ld con gestion of the lepto m e n i n x and swe l l i n g of the
b ra i n d u e to edema.
Microscopic Findings. The lepto m en i nx i s i nfiltrated by Iymphocytes and plasma
ce l l s . In the gray and wh ite matter of the b ra i n the small b lood vessels are conspicu
o u sly d i l ated . Pri mari ly in the wh ite matter aro u n d the small vei n s there are small
foci of edema a n d inflammatory infiltrates of lymp hocytes and plasma cel l s . In these
i n flam mato ry foci the myelin sheaths have been d i s i ntegrat i n g and the l i p i d contai n
ing debris i s removed by macrop hages which have a foamy cytoplasm (gitter cel ls) .
I n the demye l i n ized areas the axo ns s u rvive for a t i m e , m icrogl ial cel l s and o l i goden
d rocytes cl u ster aro u n d them (reactive gl iosis) . With Woelcke's sta i n the mye l i n ated
wh ite m atter appears b l u e to b l ac k whereas the demye l i nated areas appear as
perivasc u l a r pale gray r i n gs with i n d i sti nct borders.

260

Fig. 123. V

s m a l l vei n s ; I

i nflam matory infi ltrate; A

b ra i n tissue.

1 24. Acute purulent meningitis

( M E N I N G I T I S ACUTA PU R ULENTA)
H e m atoxyl i n -eos i n
I n the central n ervo u s system pyoge n i c bacteria most often cause p u ru lent (sup
p u rative) i nflam mation of the lepto m e n i nges and of the s u ba rach noid space. Among
the causal o rga n i s m s a re E . co l i , H. i nfl u enzae and N. m e n i ngiti d i s . Leptomeni ngitis
freq uently acco m pa n i es septicem ia, p u ru lent otitis med i a o r i n fections of the nasal
cavity and paranasal s i n uses.
Gross Findings. The b ra i n and spinal cord are swo l l e n and hype rem i c . The l ep
tom e n i n x is taut, opaq u e , gray to yel l ow and its d i l ated b lood vessels are promi nent.
The cerebral s u lci are f i l led with p u r u lent exudate which may be thin fl u i d , gray to
yel l ow or thick, green to yel low.
Microscopic Findings. The l epto m en i nx i s markedly wider over the cerebral cortex.
The con nective tissue of the l epto m e n i n x i s i nfi ltrated by cel l u lar exu date composed
mai n ly of neutrop h i l ic l e u kocytes ad m i xed with variable amou nts of eosi noph i l ic
f i b r i n filaments. This exudate f i l l s the s u barach noid space . The leptomeni ngeal
b lood vessels a re con s i de rably d i lated and congested , fi l led with e ryth rocytes. I n
severe m e n i ngitis the wal l o f the vei n s i s also i nf i l t rated by i nflam mato ry cel l s . Under
h igh magn ification the p u r u lent exudate shows masses of i n tact and degenerating
polymorp h o n u clear l e u kocytes. The n u clei of the degenerati n g cel l s are s h ru n ken
(pyknotic) o r d i s i ntegrat i n g (karyorrhectic) . The adjacent b rain tissue i s loosely
edematou s . I n severe cases pe rivascu lar r i n g- l i ke hemorrhages and leu kocytic i nf i l
trates c a n be observed .

262

Fig. 124. L

leptomen i nx ; A

b ra i n tissue; E

d i l ated blood vesse l s ;

I
p u r u l ent exudate.
-

L
A
E

1 25 . Meni ngioma
( M E N I N G EO MA)
H e m atoxyl i n-eosi n
M e n i ngioma i s a benign t u m o r of the arac h n o i d cove r i n g the b ra i n and spi nal
co rd . The tumor a ri ses from the m e n i ngothe l i a l cel l s of the arach noid vi l l i which are
mesenchymal cel l s capable of p rod u c i n g col lagen fi bers. Meni ngiomas occ u r in m id
d le-aged and elderly person s , more often in wom e n . About 1 5 % of i ntracranial
t u m o rs are m e n i ngiomas.
Gross Findings. The encaps u l ated t u m o rs measu re 0 . 5 to 5 . 0 cm are spherica l , occa
s i o n a l ly l o b u l ated or nod u lar; they cause a dep ressi o n on the adjacent b rai n tissue.
Men i ngiomas are q u ite f i rm and con ta i n calcifications which on cutt i n g with a kn ife
feel gritty and crac k l e .
Microscopic Findings. T h e tu mors p resent a wide spect r u m depe n d i n g on t h e i r
cytological and a rchitect u ral characteristics. Where t h e m e n i ngothelial cel l s pre
d o m i nate (meningotheliomatous meningioma), the t u m o r cells are densely packed and
form cel l n ests separated by trabec u lae of co n n ective tissue. The m e n i ngothelial
cel l s are oval o r s p i n d l e shaped, thei r n uclei are spheroidal and have a delicate
c h romat i n n etwo rk. The cytoplasm i s s l ightly eos i noph i l i c , the cel l borders are o ften
poorly defi ned. Freq uently the t u m o r cel l s are concentrica l l y a rranged and form
crescent-s haped nests or whorls. I n the center of these cel l conglomerates occasion
ally there are small concentrical ly l a m i n ated calcosphe rites, psammoma bodies,
which are strongly basop h i l i c . Psam moma bodies are the calcified remnants of de
generated t u m o r cel l s . Tu mors particu larly rich in psam moma bodies are cal led
psammomatous meningiomas. I n some t u m o rs the cel l s are elongate, s p i n d l e-shaped ,
para l l e l a rranged and form wavy bands ( fibroblastic or fibrous meningiomas) . A rare
type of t u m o r is markedly vascu la r and shows prolife ration of e ndothelial cel l s (an
giomatous meningioma).

264

Fig. 125. 5

stroma; T

nests of t u mor ce l l s ; P

psammoma bod ies.

1 26. Astrocytoma
H e m atoxy l i n-eosi n , g l i a stai n

Astrocytoma i s a g l i o ma com posed of wel l-d i ffe rentiated astrocytes and is a rela
tively freq uent b rai n t u m o r . It occu rs mai n ly in the cerebral hemispheres of ad u lts.
Gross Findings. The t u m o r is poorly defi ned and i nfiltrates the neighboring brain
tiss u e . On cut s u rface it i s firm, gray to wh ite and s hows smaller o r larger foci of
cystic dege n e ratio n .
Microscopic Findings. The n o rmal b ra i n tissue i s repl aced b y ste l l ate cel l s resembl
ing astrocyte s . The tumor cel l s have spherical , dark n u clei . Various types of as
trocytoma a re recogn ized : the cel l s of fibrillary astrocytomas are characterized by
abu ndant n e u roglial f i b r i l s . The tumor cel l s have spider-leg- l i ke cytoplasmic proces
ses wh ich form an i ntricate f i b r i l l a ry n etwo rk that can be visual ized with glial stai n s .
T h e cel l s of protoplasmic astrocytomas a r e p l u m per, polygo nal and do n o t have
n e u roglial f i b r i l s . These cel l s a re attached to each other by shorte r cytoplasm ic p ro
cesses. Microscopic foci of pseudocystic degen e ratio n can also be seen ( m i crocysts) .

266

Fig. 126. A

ast rocytes ; C

m i c rocyst; G

neu roglial fi b r i l s ; E

blood vessels.

1 2 7. Neuroblastoma
H e m atoxy l i n-eos i n

N e u roblasto mas a re u n d i fferentiated t u m o rs de rived from the cel l s of the sym

pathetic gangl i a . The t u m o rs may arise anywhere along the sympathetic tru n ks and
in the adrenal m ed u l la . N e u roblastomas generally occ u r in you n g ch i l d ren and are
h ig h ly mal i gnant.
Gross Findings. The t u m o rs can become large, u p to 20 cm i n d i amete r. The tumor
i s relatively wel l c i rc u m scri bed , lobu lated, soft and gray to p u rple; its cut s u rface i s
mottled w i t h f o c i of hemo rrhage and necro s i s . Areas of cal d i fication a r e freq uent
and are helpful in the rad io logic d iagnosi s .
Microscopic Findings. T h e t u m o r cel l s have t h e same size a n d sta i n s i m i l arly, resem
ble Iymphocytes but are somewhat larger. The n u clei are spherical and sta i n deep
b l u e with hematoxyl i n ; the sparse cytop l as m forms a t h i n r i m ; the outl i n es of the
cel l s are i n d i sti nct. The n e u roblasts form i rreg u l a r cel l gro u ps s u rro u nded by t h i n
septa of con n ective tissue. I n typ ical cases the t u m o r cel l s fo rm a c i rcle and occasion
ally form the d i st i n ctive Homer Wright rosettes which conta i n a central core of deli
cate loose n e u rofi b r i l lary material . The s i lver i mp regnation method demonstrates
that these fibri l s correspon d to a tangle of axonal fi laments . The tumor has larger
areas of n ecro s i s appea r i n g as homogeneous eos i noph i l ic, amorphous material, i n
which someti mes the ghosts o f t u m o r cel l s can b e recogn ized . Viable tumor cel l s
are often seen o n ly i n t h e i m mediate v i c i n ity of b l ood vessels.
Electron microscopic examination of the t u m o r cel l s reveals m icrot u b u les and elec
tron dense n e u rosecreto ry gran u les in their cytoplas m . This f i n d i n g is of great help
in estab l i s h i ng the correct d i agnosis.

268

Fig. 127. N

n e u roblasts ; M

m i toses ; R

rosettes.

1 2 8. G l ioblastoma m ultiforme
H e m atoxyl i n-eosi n

This i s one of the most aggressive malignant t u m o rs of the central nervou s system .
It most freq uently occu rs i n 40 to 50-year-ol d men . I n typical cases it affects the
frontal lobe of the cereb ral h e m i sp heres.
Gross Findings. The t u m o r appears as a ci rcu mscri bed soft mass situated i m
mediately u n der the cereb ral co rtex. The t u m o r shows an extraord i narily vari egated
cut s u rface. The moist, fleshy white t u m o r tissue is mottled with geographic areas
of tan , clay-l i ke d ry n ecros i s , p u rp l e or rust-col o red foci of hemorrhage, and smaller
o r larger cystic space s .
Microscopic Findings. The t u m o r is conspicuously cel l u lar, i t s cel l s a r e u n u s ually
variable in s hape, size and sta i n i ng p ro pe rties. The ce l l s can be spherical , polygonal ,
oval and elongated , s p i n d l e-s haped (pleomorphism). Li kewise the ce l l n u clei sig
n ificantly vary in shape and i n thei r c h romat i n content. B izarre, m u ltin ucl eated
t u m o r giant cel l s with a wide seam of eosi noph i l ic cytoplasm are freq uently see n .
Abnormal m u ltipolar m i toses can a l s o b e observed . I n some areas t h e t u m o r cel l s
rese m b l e matu re astrocytes . T h e cel l u lar neoplasm contai ns foci o f hemorrhage and
necrosis, with t u m o r cel l s fo r m i n g pal i sades aro u n d necrotic centers . The stroma is
h i gh ly vascu lar. A characteristic fi n d i n g wit h i n and adjacent to the tumor is the pro
liferation of en dothel ial cel l s i n the capi l l aries which significantly na rrows their
l u me n . Some bl ood vessels are occl uded by t h ro m b i .

270

Fig. 128A . N

necros i s ; T t u mor; A b ra i n tissue.

Fig. 1288. 0 t u m o r giant cel l s .
-

1 2 9. Schwannoma
( N E U RO LEMM OMA)
H e m atoxyl i n -eos i n
N e u rolemmoma i s a benign t u m o r of peripheral nerves and nerve roots which
originates from the Schwa n n cel l s . Most freq uently it ari ses from b ranches of sen
sory n e rves o n the flexor s u rface of extrem ities, the n eck or the med i asti n u m .
Gross Findings. T h e t u m o r i s 0 . 5 t o 6 . 0 c m , encaps u l ated a n d has a lobu lated ar
ch itectu re . I ts soft s u b stance i s tan to gray, someti mes glassy and transparent. On
cut s u rface it is friable with scattered smaller cysts.
Microscopic Findings. Two types of t u m o rs can be d i st i n g u i shed . Antony type A
schwan n omas have a fascic u l a r arch itect u re , thei r elongated , s p i n d l e cel l s fo rm com
pact b u nd le s . The long, ci gar-shaped n u clei have rou n ded ends and show a loose
ch romatin n etwo rk. The n uc l e i of the t u m o r cel l s are l i ned up in rows paral l e l l i n g
t h e l o n g axis of t h e cel l s , creat i n g a pattern o f a picket fence. T h e rows o f dark b l u e
n uclei are periodically alternat i n g w i t h b a n d s o f eosi noph i l i c fibri l lar cytoplasmic
p rocesses . The fascicles of cel ls are occasionally i nterlacing and fo rm bands of wavy
and whorl i n g con f i g u rati o n . There are also homogeneous eosi noph i l ic hya l i n ized
areas i n the t u m o r . Antoni type B schwa n nomas have a n etwo rk- l i ke ( reti cu lar) his
tologic arch itecture; they have a loose, myxoi d gro u nd s u bstance in which cel l s of
varia b l e (spherica l , polygo n a l , ste l l ate) shape are scattered o r arranged i n a s p i ral
pattern . Macrophages with a foamy cytoplas m can be seen in small gro u p s . I n the
stroma there are small cysts f i l l ed with ace l l u lar eos i n o p h i l i c f l u i d .

272

Fig. 129. Anto n i A type schwannoma.

rows of cel l nucl e i ; C fi b r i l lar cytoplasmic processes.
-

APPEN D I X

I MM U N O H I STOCH EM I STRY

I . I mm u noh istochemical d ifferentiation of

tu mors of mesenchymal and m uscular origin
T h e so-cal led i ntracytoplas m i c i ntermed iate fi laments have tissue-specific chemi
cal characteristics which perm it the i r i m m u no h i stochem ical demonstration . These
p roperties can be u sed to recogn ize the cel l of origin of con n ective tissue tumors
which co u l d not be d iffe rentiated with t rad itional h i stological methods (sta i n s ) . Vim
entin characterizes mesenchymal cel l s a n d primarily serves to d i fferentiate them
from epithelial cel l s . In o n e of our cases ( I a) the h i gh ly pleomorphic cel l s of an
anaplastic mal ignant t u m o r reveal a stro n g reacti o n with anti body to vi menti n . S i nce
other markers are n egative, the tumor i s considered to be a fibrosarcoma (Case 1 a) .
O u r other case ( I b) s hows a mesenchymal t u m o r i n a rare location (kid ney). The
e l o ngate, but p leomorp h i c t u m o r cel l s show a stro ng i ntracytoplasmic reaction with
smooth m u scle acti n-specific antibody. This f i n d i n g i s co nsistent with a leiomyosar
coma (Case 1 b ) . These i m m u no h i stoch e m i cal reactions use the peroxi dase-anti
peroxidase ( PAP) method , the sites of anti body-enzyme complex are visual ized with
a c h ro m oge n , d i a m i n obenzi d i n e ( DAB) , giving a b rown reacti o n product.

276

Fig. I(a) F i b rosarcoma. Strongly positive reaction ( b rown precipitate) for vimentin
i n cytoplasm of t u m o r cells (Vp) .
Fig. I(b) Leiomyosarcoma. Positive reaction ( b rown preci pitate) for smooth m u scle act i n
i n cytoplasm of t u m o r cells (Ap) .

Vp

Vp

Ap

1 1 . Amelanotic form of mal ignant melanoma

d iagnosed with i m m u noh istochem ical

methods
The amelanotic f o r m of malignant m e l a n o m a often p resents a serio u s differential
d iagnostic p rob l e m . Cel l s (and t u m o rs) of neu ral crest origin are 5-1 00 positive,
therefore, the cytoplasm of most mal ignant melanoma cel ls wi l l sta i n for 5-1 00. This
also has been i l l u strated by our Case 1 1 a . In add i t i o n , the tumor cel l s also gave a
positive reacti o n for viment i n . 5 i n ce othe r tu mors (e. g. n e u roge n i c or h i stiocytic)
are also freq uently 5 - 1 00 positive, it was necessary to u se other antibodies to ass i st
in the d i fferential d iagnosi s . I m m u no h i stochem i cal reactions with pancytokerat i n
anti body cocktai l and anti body H M B45 , a p remelanosome glycop rote i n , were also
perfo rmed . The reaction to pancyto keratin was negative and the reacti o n fo r H M B45 ,
w h i c h is strongly specific fo r melanoma , was pos itive (Case 1 1 b ) . T h u s, the tumor
p roves to be a mal ignant melanoma. Because pri mary melanomas of the vagina are
rare, the poss i b i l ity of a metastasi s also had to be co n s i de red. H owever, no
melanoma was fo u n d at other sites and there was no h i story of a previously removed
t u m o r or a s k i n lesi o n .

278

Fig. I/(a) Positive reacti o n ( b rown precipitate) for 5-100 i n cytoplasm

of tumor cel l s (5).
Fig. I/(b) Positive reaction ( b rown precip itate) for H M B 45 in cytoplasm of tumor cells ( H ) .

, '"
.,

'" -.

..

s
.. ,

I l l . I mm unoh istochemical reactions

identifying mal ignant tumor as epithel ial and
of prostatic o rigin
The cytoplasm of most epith e l i al t u m o r cel l s i s positive fo r cyto kerat i n . The epithe
l ial membrane antigen (EMA) is exp ressed on the s u rface of n u m e ro u s epithel ial ,
mai n ly glan d u lar, cel l s . Cyto kerat i n (briefly : kerat i n ) is a fam i ly of n u merous related
p rote i n s , but in rou t i n e s u rgical pathology a pancytokerat i n (briefly : kerat i n ) anti
body is employed, which reacts with most kerat i n s u btypes. In the p resented case
a mal ignant t u m o r of u n dete r m i n ate o ri g i n was fou n d i n the wal l of the rect u m ,
covered b y normal appeari n g m ucosa. T h e t u m o r showed gland- l i ke structu res a n d ,
th erefo re, a p ri mary adenocarcinoma of the rect u m cou l d n o t b e ru led out with
conventional h i sto logical stai n s . The t u m o r cel l s showed a strong i m m u nohis
tochem ical reaction (PAP, DAB) fo r kerati n (Case I I I a) i . e . the tumor has been of
epithelial origi n , a carci noma. Fol lowi n g t h i s , the i m m u n o h i stoche m i cal reaction for
p rostate-specific antigen (PSA) was performed and it gave a positive res u lt (Case
I I I b ) , i n d icative of a p r i mary adenocarci noma of p rostatic origi n . Based on this evi
dence hormone therapy was s u ccessf u l .

280

Fig. /l1(a) Positive reacti o n ( b rown precipitate) with anti bodies to keratin i n
cytoplasm o f tumor cel l s (C) .
Fig. /l1(b) Postive reaction (brown p recipitate) for prostate-specific antigen (PSA) i n cytop lasm
of tumor ce l l s (P) .

'.

. .'
.*
.

i'

.'-'
- .

"

0
c

I V. D iagnosis and subtyping of malignant

lym phomas with i m m u noh istochemical
methods.
Non-Hodg k i n type mal ignant t u m o rs o f lymphoid tissue are a l m ost always mon oc
lonal , i . e . , they are p red o m i nantly composed of one lymphoid ce l l type. These
mal ignant lymphomas can be B cel l o r T cel l neoplasms. B cel l lymphomas may
p roduce an i m m u noglob u l i n which, characte ri stical ly, is identical in a l l cel l s of a
given t u m o r . T h i s feature of the t u m o r cel l s can be u sed fo r the i m m u no h i stochem
ical demonst rati o n of the so-cal led l ight chai n s , i. e. kappa and lam bda polypeptide
chai n s , because thei r exc l u sive p resence i n d i cates monoclonal ity. Th i s i m m u nohis
toch e m i cal method is often appl i ed to d i fferentiate between a reactive ( polyclonal)
and neopl astic (monoclonal) lym phoid i nfi ltrate .
The fi rst case i s a fol l i c u l a r lymphoma of B lym p hocytic l i neage. The cytoplasmic
m e m b ra n e of most tumor cel ls gives a positive reaction with a pan-B anti body, other
t u m o r cel l s do n ot mark with either pan-B o r pan-T antibodies (Case IV a) . O n f u rther
exam i nation the tumor cel l s gave an u n e q u ivoca l ly positive reacti o n for the kappa
l ight chai n .
The second case i s a mediastinal lymphoma of c h i l dhood, i n which the cytoplasmic
m e m b rane of the majo rity of the tumor cel l s reacts with pan-T anti body (Case I V b).
(Al kal i n e phosphatase was u sed as an e nzyme label and accou nts for the p u rple
col o r p roduct . ) S i n ce the t u m o r cel l s did not react with the pan-B anti body, the
lymphoma has been con s i d e red of T-cel l l i neage. The B o r T cel l origin of mal ignant
lymphomas i s , beside othe r h isto logic f i n d i n gs and c l i n ical stag i n g , i m portant from
a therapeutic p o i nt of view .

282

Fig. IV(a) Positive reaction ( b rown precip itate) w i t h pan-B cel l marker
in the cytoplasm of the majority of tumor cel ls (B).
Fig. I V(b) Positive reaction (dark b l u e precip itate) with pan-T cell marker on the su rface
of the majo rity of tumor cel l s (T).

v. I mm u nohistochem ical demonstration of

estrogen and progesterone receptor proteins

in carci noma of the breast
In a sign ificant percentage of b reast cancers, particu larly in premenopausal
wom e n , the t u m o r cell n uclei possess receptors for steroi d hormones, specifi cal ly
for estrogen and p rogestero n e . Tumors which have such hormone receptors u s ually
respond wel l to anti -estrogen ( e . g . Tamoxifen) treatment, whereas tu mors which
lack such receptors a re refracto ry to therapy with hormo ne-antago n i sts, o r even may
behave paradoxically. Therefo re, it is mandatory to perfo rm i m m u n o h i stochemical
stu d i es of these hormone receptors in b reast carci noma (either on a bi opsy or a
mastectomy speci men) .
O u r case i s an i nfiltrati n g adenocarci noma of d u ct origi n , i n which 90% of the
t u m o r cel l s are positive fo r estrogen receptor prote i n ( Case V a) and 80% react for
p rogesterone receptor p rotei n (Case V b) . These res u lts have been uti l ized i n the
therapy of this patient. The hormone receptors were demonstrated in the paraffin
e m bedded tissue (PAP, DAB ) , but there are commercially avai lable antibodies which
wi l l react o n ly with cel l s o n frozen sections using i m m u n ofl u o rescence tech n i q u e .
S i n ce fo rma l i n fixation may render t h e spec i m e n u n s u itable fo r s o m e i m m u nohis
toc h e m i cal methods, it i s i m portant fo r the s u rgeon to know before the operation
w h i c h i m m u n e serum and method the consu ltant patho logist wi l l use and proceed
acco rd i n gly.

284

Fig. V(a) Positive reaction ( b rown p reci pitate) for estrogen receptor prote i n
i n n uclei of majority o f t u m o r cel l s (Oe) .
Fig. V(b) Positive reaction ( b rown precipitate) for progesterone receptor prote i n in n uclei
of majority of tumor cel l s (Pr).

Oe

Pr

B i bl iography

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d e rs Co . , P h i lad e l p h i a, 1 994.
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Lo u is , 1 996.
3 . Elder 0, E l e n i tsas R, J aworsky C , J o h nson B J r . Leve r's H i stopathology of the
S k i n . 8th Ed . L i p p i ncott-Raven , P h i ladelph ia, 1 997.
4 . Enzi n ge r FM, Weiss SW. Soft Tissue Tumors . 3 rd Ed. CV Mosby, St. Lo u i s , 1 995.
5 . F l etche r CDM. Diagnostic H istopathology of Tumors. 3 rd Ed. Vol 1 - 1 1 . C h u rc h i l l
Livi n gsto n e , Ed i n b u rg h , 1 995 .
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1 970 .
7 . G raham 0 1 , Lantos P I . G reenfield's N e u ropatho logy. 6th Ed. Vol 1 - 1 1 . Arno l d ,
Lon d o n , 1 997.
8 . Ku rman RJ . B l a u stei n ' s Pathology of the Female Gen ital Tract. 4th Ed . Springer
Verlag, N ew York, 1 994.
9 . Lewi n KJ , Riddel l R H , Wei n stei n WM. Gastro i ntestinal Pathology and its C l i n ical
I m p l icat i o n s . Igaku-Sho i n , Tokyo , 1 992 .
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and 2 b . Oxford U n iversity Press, Oxfo rd , 1 992 .
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WB Saunders Co . , Phi lad e l p h i a , 1 993 .
1 2 . Rob i n so n H BG , M i l ler A S . Color Atlas of O ral Pathology. 5th Ed. J B Lippincott,
P h i l adel ph ia, 1 990.
1 3 . Rosai J. Ackerman's S u rgical Pathology. 8th Ed . Vol 1 - 1 1 . CV Mosby, St. Lou i s ,
1 996.
1 4 . S i lverberg SG, DeLe l l is RA, Frable WJ . Pri nci ples and Practice of S u rgical Patho
logy and Cytopathology. Vol I - I l l . C h u rch i l l-Livi n gston e , N ew York, 1 997.
1 5 . S hafe r WG , H i ne MK, Levy BM. A Textbook of O ral Pathology. 4th Ed . WB Saun
ders Co . , Phi lad e l ph i a , 1 983.
1 6 . Sternberg SS. H i stology for Patho logists. 2 n d Ed. JB L i p p i n cott, P h i ladelphia,
1 997.
1 7 . Stern berg SS, Anto n i o l i DA, Carte r 0 , M i l l s SE, O berman H H . Diagnostic S u rgi
cal Pathology . 2 n d Ed . Vol 1 - 1 1 . Raven Press, New York, 1 994.
1 8 . U nd e rwood J C E . General and Systematic Pathology. 2 n d Ed. C h u rc h i l l - Livingsto
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1 9 . Wen i g BM. Atlas of H ead and N eck Pathology . WB Sau n ders Co . , Phi ladelphia,
1 993.
286

I ndex

Abscess,
cerebral 56
p u l monary 56
Actinomycos i s ,
cervicofacial 58
Adenocarci noma,
of b reast 88
of colon 84
of prostate 224, 280,
of thyro i d , pap i l lary 256
Adenoid cystic carci noma 1 72
Adenoma
of ad renal co rtex 258
of sal ivary glands,
pleomorph i c 1 04
Ad renal cortex,
adenoma of 258
Alco h o l i c hepatitis 1 96
Amelob lastoma, of jaw 1 68
Amyloidosis
of k i d ney 18
Aorta
atherosclerosis of 1 22
cystic med ial necrosis 1 24
Appendicitis
acute 1 84
Astrocytoma 266
Atherosclerosi s ,
aortic 1 22
Atrophy
of testis 36

Basal cel l carci noma

of s k i n 82

Bone
chondroma of 246
Paget's d isease of 244
B ra i n
abscess 5 6
encephalomye l itis, postvacci nal 260
i n farct 42
l i q uefactive n ecrosi s of 42
neoplasia of,
astrocytoma 266
g l i o bl astoma m u ltiforme 270
Tay-Sachs-Schaffer d i sease 22
B reast
adenocarc i noma of 88, 284
estrogen and p rogesterone
receptors 284
fi broadenoma of 240
fib rocystic d i sease of 238
B ronchoge n i c carc i n oma, small cell 1 42
B roncho p n e u m o n i a 1 34
B u e rger's d i s ease 1 26
c

Can d i d iasis
of esophagus 66
Carc i noma
adenocarc i noma of p rostate 224, 280
b ro n c h io loalveolar, of l u n g 1 44
e m b ryonal cel l , of testi s 1 22
smal l cel l , of l u n g 1 42
squamous cel l
o f l u n g 80
of uteri n e cervix 232
of p rostate 224, 280
renal cell 2 1 6
o f s k i n , basal cell 82
transitional cel l ,
of u ri nary bladder 2 1 8

287

Cervicofacial acti n omycosis 58

Cervix, ute r i n e ,
carci noma o f 232
eros i o n of 230
Cholestasi s , l iver 28
C h o n d roma 246
C h o n d rosarcoma 1 02
Choriocarci noma 1 1 0
Ci rrhosis
m icronod u l a r 1 98
Col itis,
u l cerative 1 88
Col o n
adenocarci noma of 84
adenoma of 1 90
adenomatou s polyps of 1 90
Cro h n ' s d i sease 1 82
Cyst
rad i c u l a r 1 60
Cystadenocarcinoma
of ovary 86
Cystadenoma
of ovary
m uc i n o u s 234
serous 234
Cystic med ial n ecrosis of aorta 1 24
Cytomegaloviral i nfection i n parotid 1 56

Degen e ratio n ,
fatty, o f l iver 1 6
vac u o lar, o f kid ney 1 4
D iabetes m e l l itus,
glomeru loscl e rosis i n 2 1 0

288

Edema, l u ngs 50
E m b ryonal carci noma
of testis 222
Emp hysema, l u ngs 32
Encephalomye l it i s
postvacc i n al 260

Endocard i u m
f i b roelastosis o f 120
Endometri u m
hyperplasia 46

Enterobius vermicularis i n appendix

1 86
E p u l i s 70
Eso p hagitis
cand idal 66
F

Fat necrosis 68
Fatty
degeneration of l iver 1 6
i nfi ltration o f myocard i u m 1 1 4
Fibrinous
pericard itis 54
p n e u m o n i a 1 32
F i b roadenoma of b reast 240
F i b rocystic di sease i n b reast 238
F i b roel astosis, endocard ial 1 20
Fi b rosarcoma 276
Foreign body g ra n u loma 68
G

Gastritis
c h ro n i c 1 74
G i ant cel l g ra n u loma of o ral cavity,
peri pheral 70
G l ioblastoma m u ltiforme 270
Glomeru loneph ritis
acute poststreptococcal 204
membranopro l i ferative 206
G lomeru losclerosis
d iabetic 21 0
Goiter
n o d u l a r 250
G ra n u lar cel l tumor 1 66
G ra n u loma
foreign body type 68
G ran u l omato u s thyroiditis 254
G ran u l osa cel l tu mor, of
ovary 236

G raves d i sease 252

Gum,
giant cel l gra n u loma 70

Hemangioma,
cap i l lary 96
cave rnous 96
Hemosiderosis 26
Hepatiti s ,
acute viral 1 92
alcoholic 1 96
chro n i c 1 94
Hepatocel l u lar ca rci noma 200
H i stiocytosis
sinus, lymph node 1 46
Hodgki n ' s d i sease
lymph nodes i n 1 50
Hya l i n e membrane d i sease 1 38
Hydatidiform mole 228
Hyperplasia,
endometri u m 46
prostate 48
Hyperthyroidism 252
Hypokalemic n e p h ropathy 1 4

I n farct
of bra i n 42
of kid ney, anemic 38
of l u ng, hemorrhagic 40
of myocard i u m 1 1 6

Jaund ice
cholestatic 28

Kaposi's sarcoma 1 30
Keratosis
of o ral m ucosa 1 64
Kid n ey
i n amyloidosis 1 8
carci noma,
renal cel l 21 6
degeneration, vacuolar 1 4
en d-stage d i sease 214
i n farct of 38
polycystic d i sease 34
Wi l m s ' tumor 1 06

Lae n nec's ci rrhosis 1 98

Larynx
squamous pap i l l oma of 78
Leiomyoma
of uterus 98
Leiomyosarcoma 276
Leu ke m i a 1 48
i nf i ltrate i n l iver 1 48
lymphocytic, ch ro n i c 1 48
myeloge n o u s , c h ro n i c 1 48
Leu koplakia
of o ral m u cosa 1 64
L i pogra n u l o m a 68
Liver
alco h o l i c hepatitis 1 96
centri l o b u lar n ecro s i s 44
cho lestasi s 28
fatty 1 6
hemosiderosis 26
N i e man n-Pick d i sease 20
Lung
abscess 56
carci noma
b ronchioloalveo lar 1 44
smal l cel l 1 42
squamous cel l 80
c h ron ic passive con gestion 24
edema 50

289

290

e m p hysema 32
i n farct, hemorrhagic 40
in resp i ratory d i stress synd rome
1 38
s i l i cosis 1 40
squamous cel l carci noma 80
tubercu losis 60
Lym phadenitis
tuberc u l o u s 62
Lym ph n ode
metastas i s to 96
s i n u s h i stiocytos i s 1 46
tubercu l o u s 62
Lym phoma
B cel l 282
Hodg k i n ' s 150
n o n - H odgki n ' s 1 52
T cel l 282

Necros i s
caseo u s
i n tubercu losis 6 0 , 62
fat 68
kid ney, anemic 38
l iver, cent rilobular 44
l i q u efactive b ra i n 42
l u ng, h emo rrhagic 40
Neph rosclerosis
benign 202
N e u ri lemmoma 275
N e u rob lasto ma 268
Nevu s , pigmented 30
N i e mann-Pick d i sease 20
N i pple
Paget d i sease of 242

Medial
cystic n ecrosis of ao rta 1 24
Melanocyte, nevus 30
Melanoma
mal ignant 1 08, 278
Meni ngioma 264
M e n i ngitis
s u p p u rative 262
Metastasis
lymphatic 90
M i k u l i cz d i sease 1 62
M ixed tu m o r , paroti d gland 1 04
Mole, hydati d ifo rm 228
M o l l uscum contagios u m 76
Mycobacte ri u m tu bercu losis 64
Myeloma
m u lt i p l e 1 54
Myocard itis
i n rheu matic h eart d isease 1 1 8
Myocard i u m
fatty i nfi ltration 1 1 4
fibros i s 1 1 4
i n farction o f 1 1 6
Myxo ma 94

Odontoge n i c cyst 1 60
Osteosarcoma 248
Ovary
cystadenocarcinoma of 86
cystad enoma
m uc i n o u s 234
sero u s 234
gra n u losa cel l tumor of 236
thecoma 236

Paget d i sease
of bone 244
of n i pple 242
Pap i l lary carci noma
of bladder 21 8
of thyro i d 256
Papi l loma
of l arynx, squamous cel l 78
Parotid gland
cytomegalovi ral i n fection 1 56
pleomorp h i c adenoma 1 04

Peptic u lcer d i sease

chronic 1 76
Periarteritis nodosa 1 28
Pe ricarditis
fibrinous 54
Pe riodontal ( rad icu lar) cyst, apical 1 60
Placenta
hydatidiform mole of 228
Plasma cel l neoplasia 1 54
Pleural fl u i d ,
tumor cel l s i n 92
Pneumocystis carinii p n e u m o n i a 1 3 6
Pn eumonia,
lobar 1 32
Pneumocystis carinii 1 36
Polyarteritis nodosa 1 28
Polycystic d i sease, of kidneys 34
Postvacci nal encephalomye l itis 260
Pregnancy 226
Prostate
adenocarci noma 224, 280
nod u lar hyperplasia 48
Pyelonephritis, c h ro n i c 208

Sarcoma
Kapos i 's 1 30
osteogen i c 248
Schwan noma 272
Sem i n oma 220
S i al adenitis, chronic 1 58
Signet ring cel l carci noma of stomach 1 78
S i l i cosi s , p u l monary 1 40
S i n u s h i stiocytosis of lymph node 1 46
Skin
basal cel l carci noma of 82
hemangioma 96
mol l u scum contagiosu m 76
verruca vu l garis 74
Squamous cell carc i noma
of l u n g 80
of uterine cervix 232
Squamous cell papi l loma,
of l a rynx 78
Stomach
adenocarci noma, m u c i n o u s of 1 80
early 1 78
s ignet r i n g cell type 1 78
peptic u lcer, c h ro n i c of 1 76

Rad icu lar (apical periodontal) cyst 1 60

Renal cel l carci noma 21 6
Respi ratory d i stress synd ro m e 1 38
Rhabdomyosarcoma 1 00
Rheu matic fever di sease
myocard itis of 1 1 8
s

Salivary gland
adenoid cysti c carci noma 1 72
chronic i nflammation 1 58
cytomegalovi ral i n fection 1 56
Iymphoepith elial lesion of, benign 1 62
in M i k u l icz's d i sease 1 62
pleomorp h i c adenoma ( m ixed tu mor)
of 1 04
in Sjogren's synd rome 1 62
Warthi n's t u m o r of 1 70

Tay-Sachs-Schaffer d i sease 22
Testis
atrophy 36
e m b ryonal carci noma of 222
sem i noma of 220
Theco ma, of ovary 236
Th ro m boangitis o b l iterans 1 26
Thro m bosis 52
Thyroid gland
carc i noma, pap i l lary 256
hyperfu n ction of 252
n od u lar goiter 250
Thyroiditis
DeQu e rva i n ' s gra n u l omatou s 254
Transitional cell carci noma
of u ri nary b ladder 2 1 8
Tuberc u l osis
kid ney 212

291

lymphad e n i t i s 62
m i l iary 60
of lymph n odes 62
Tumor
markers i n 276, 278, 280, 282
T u m o r cel l s
i n pleu ral f l u i d 92

U l ce rative colitis 1 88
U ri nary bladder
tran sitional cel l carci noma of
papi l l a ry 21 8
Ute r i n e cervix
carc i noma of 232
erosion 230
l eiomyoma of 98

292

Vacuolar degeneration of, ki dney 1 4

Verruca vu lgaris 74

Warth i n 's t u m o r of sal ivary gland 1 70

Wil ms' t u m o r 1 06
Wou n d heal i n g
b y pri mary i ntenti on 72