SURGICAL PATHOLOGY OF THE OVARY

Anatomy.
· measures 4 x 2 x 1 cm.; weighs about 5 Gm.
· outer surface covered by a layer of cuboidal or low columnar epithelium (surface or germinal
epithelium)
· outer cortex contains ovarian follicles; inner medulla contains the blood vessels and nerves
· maturation of follicle: primordial follicle  primary follicle  mature Graafian follicle  corpus
luteum  corpus albicans.
Primordial follicle: oocyte surrounded by a thin layer of granulosa cells and stroma
Primary follicle: oocytes enlarge, follicular granulosa cells become cuboidal or columnar
Mature graafian follicle: a cavity (antrum) develops within the nest of granulosa cells and gradually
enlarges, pushing the ovum to one side. The stroma surrounding the follicle differentiates into two
layers: inner theca interna, outer theca externa.

Non-neoplastic cysts and related disorders.

1.. Surface epithelial cysts (germinal inclusion cysts)
· frequently occur near or after menopause
· derived from invaginations of surface epithelium; lined by one layer of cuboidal epithelium
· asymptomatic, but are considered to be the site of origin of some true neoplasms of the ovary

2. Cystic follicle
· cystic changes may occur during the course of maturation and regression of the normal follicle 
cystic follicle, cystic corpus luteum, cystic corpus albicans.
· usually less than 3 cm. in diameter

3. Polycystic ovarian disease

· a spectrum of clinical pictures, including asymptomatic patients, Stein-Leventhal syndrome,
familial polycystic ovarian disease, hyperthecosis.
· Stein-Leventhal syndrome: infertility, hirsutism, amenorrhea, obesity, menometrorrhagia
· PCOD may also be associated with virilization, due to secretion of androgens by theca cells and
the hyperplastic stroma
· Pathology: thickened white cortex with multiple cysts lined by granulosa and theca cells; usually
no corpora lutea or albicantia; stromal hyperplasia.

Classification of Ovarian Tumors (WHO)

I. Common Epithelial Tumors (Surface Epithelial-Stromal Tumors)
1. Serous tumors: benign, of low malignant potential, malignant
2. Mucinous tumors: benign, of low malignant potential, malignant
3. Endometrioid tumors: benign, of low malignant potential, malignant
4. Clear cell tumors: benign, of low malignant potential, malignant
5. Brenner tumors (transitional cell tumors): benign, of low malignant potential, malignant
II. Sex Cord-Stromal Tumors
1. Granulosa-stromal cell tumor: adult type, juvenile type
2. Thecoma-fibroma
3. Sertoli-Leydig cell tumors (androblastomas)
III. Germ Cell Tumors
1. Dysgerminoma
2. Yolk sac tumor (endodermal sinus tumor)
3. Embryonal carcinoma
4. Choriocarcinoma
5. Teratomas: mature, immature, monodermal and highly specialized
IV. Metastatic Tumors
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COMMON EPITHELIAL TUMORS OF THE OVARY

· 60% of all ovarian neoplasms
· 80-90% of all primary ovarian malignancies
· derived from the surface epithelium, which differentiates along one or more of the mullerian cell types:
endosalpingeal (serous), endocervical (mucinous), endometrial (endometrioid), mesonephroid (clear
cell), and urothelial or transitional (Brenner).
· “Borderline” ovarian tumors (tumors of low malignant potential) [WHO, FIGO]
 a subset of patients with much more favorable prognosis than the “usual” surface epithelial
carcinomas
 WHO definition: a greater proliferation than cystadenoma but lacking invasive or destructive
growth (stromal invasion)
 All definitions of borderline tumors take into account only the histological appearances of the
ovarian neoplasm; the presence or absence of extraovarian spread plays no role in the definition of
borderline tumors. Even if extensive extensive extraovarian deposits are present, it will still be
classified in the borderline category if it fulfills the histologic criteria for that diagnosis. (Fox,
1989)

Benign Serous Tumors (Serous cystadenoma, serous cystadenofibroma)

· 25% of all benign ovarian neoplasms
· peak incidence: 4th and 5th decades
· bilateral in 12-20% of cases
· gross: unilocular, but may be multilocular cysts with polypoid excrescences
· microscopic: papillary processes lined by a single layer of epithelium resembling tubal mucosa

Serous Tumors of LMP (borderline serous tumors, atypically proliferating serous tumors)
· 10-15% of ovarian serous tumors
· bilateral in 25-30% of cases
· 20-40% are associated with papillary serous epithelial lesions on pelvic viscera or omentum
("implants")
· gross: often cystic, with papillary excrescences; NOT grossly distinguishable from serous carcinoma.
· microscopic criteria: 1. nuclear stratification up to 3 layers
2. atypia
3. micropapillary formation
4. absence of stromal invasion

· survival rate: Stage LMP Serous CA

1 95% 54%
1-4 91% 23%

· Survival in S-LMPs (953 cases)

Stage I 99%
Stage II, III. IV 92%
Dev. of invasive CA 0.7%

· patients without extraovarian disease after a thorough staging lap can be expected to survive without
recurrence
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· in high stage S-LMPs, evaluation of implants is important in guiding therapy:

= Non-invasive implant: circumscribed, sharp demarcation, mild to moderate
atypia, rare cribriforming
= Invasive implant: irregular, jagged infiltration into underlying normal tissue,
marked atypia (malignant cytology), cribriform nests
Mortality rate with implants: = Non-invasive 7%
= Invasive 33%
S-LMPs with invasive implants should be removed from the borderline category.
· patients with extraovarian disease: 30-40% succumb ultimately to progressive disease, "benign"
complications, or side effects of therapy.

· S-LMP with microinvasion: individual cells/clusters within stromal stalks or papillae, or cribriform
pattern, less than 3 mm. Microinvasion does not worsen the prognosis beyond that of serous tumor of
low malignant potential.

Malignant Serous Tumors (serous cystadenocarcinoma)

· 40-50% of malignant ovarian neoplasms
· bilateral in two-thirds of cases
· age distribution: 45-65
· widely disseminated disease in 80-85% at time of diagnosis
· Microscopic: stromal invasion >3 mm.
malignant cytologic features, even in the absence of stromal invasion
· 10-yr survival rate 5-25%
· full staging laparotomy is vital, "upstaging" more than 1/3 of cases apparently confined to the pelvis

Benign Mucinous Tumors (mucinous cystadenoma)

· 20-25% of all benign ovarian neoplasms
· age distribution: 3rd to 5th decades
· bilateral in only 2-3%
· gross: multilocular cysts, can become very large (up to 50 cm.)
· microscopic: endocervical or intestinal type of epithelium in single layer, with no evidence of
atypia/mitosis, no tufting or papillae

Borderline Mucinous Tumors (atypically proliferating, of low malignant potential)

· 14% of all mucinous tumors
· peak incidence in the 30's
· grossly similar to the benign lesion
· microscopic: multilayering (2-3 cell layers), micropapillary formation (filigree pattern), nuclear
atypia, mitotic activity, no stromal invasion
= stromal invasion: irregular jagged nests in granulation tissue-like fibrous tissuemay be extremely
focal, hence the importance of adequate sampling

· Survival rate: Stage I almost 100%

Stage II & up 40-50%
· High stage mucinous LMPs of the intestinal type have pseudomyxoma peritonei as manifestation of
extraovarian tumor, with a predictable course of recurrent mucinous ascites, bowel obstruction, and
death (50% mortality at 5 years). Explore/remove the appendix.
· Pseudomyxoma peritonei: extensive mucin deposits unaccompanied by epithelium, or accompanied
by a disproportionately small volume of bland epithelium.
= the ovarian neoplasm is almost always benign or M-LMP, yet clinically aggressive
and lethal
= histogenesis: (1) chronic spillage of mucinous epithelium from appendix/ovary
(2) mesothelial cell metaplasia

Malignant Mucinous Tumors (mucinous cystadenocarcinoma)

· 5-10% of malignant primary ovarian neoplasms
· 4th-7th decades
· 15-20% bilateral
· gross: multilocular cysts, with solid areas, necrosis, hemorrhage
· microscopic: highly malignant features, stromal invasion, cribriform pattern
· mucinous tumors may be lined by intestinal or mullerian (endocervical) type of epithelium; intestinal
type cells are more common in borderline and invasive mucinous tumors.
· 5-year survival rate: overall - 40%

Endometrioid Tumors
· 80% of ovarian endometrioid tumors are frankly malignant
· 20-25% of all ovarian carcinomas
· bilateral in 28% of cases
· age incidence: 5th-6th decades
· Microscopic features of endometrioid differentiation:
(1) Architecture: = villoglandular or glandular
= round gland lumens
(2) Epithelium: = resembles cells of endometrial hyperplasia/carcinoma
= squamous differentiation common
· 20-25% associated with endometrial carcinoma
When endometrioid carcinoma of the ovary occurs in associated with endometrial adenocarcinoma,
does this represent FIGO Stage IIA ovarian carcinoma, Stage III endometrial carcinoma, or dual
synchronous primary tumors?
Consider the two lesions as independent primaries when:
1. the tumors display different histologic types
2. the endometrial tumor is less than 2 cm., with minimal or no evidence of myometrial invasion
3. there is evidence of endometriosis with malignant transformation or associated with hyperplastic
changes adjacent to the endometrial adenocarcinoma.
· usually better overall prognosis than mucinous or serous carcinoma

Clear Cell Tumors: most clear cell tumors are malignant; benign and borderline clear cell tumors are
uncommon.

Malignant Clear Cell Tumors

· 5-10% of all malignant ovarian epithelial tumors
· 5th-7th decades
· 50-70% associated with pelvic endometriosis
· microscopic: 1. sheets of polyhedral clear cells (abundant glycogen and lipid)
2. tubulo-papillary pattern lined by clear, hobnail, or eosinophilic cells.
· 5-yr survival, stage I - 80-90% (Brescia, 1989)

Transitional Cell (Brenner) Tumor

· derived from surface epithelium which undergoes urothelial metaplasia
· 1-2% of primary ovarian neoplasms
· mean age: 50
· majority are benign; less than 2% are borderline or malignant
· epithelial component consists of small solid islands of transitional cells with grooved nuclei (coffee
bean appearance)
· stromal component consists of fibrous tissue surrounding islands of epithelium

SEX CORD STROMAL TUMORS

The sex-cord stromal tumors comprise all ovarian neoplasms derived from the embryonic sex cords,
stroma, or both. These may contain granulosa cells, theca cells, Sertoli and Leydig cells in varying
combinations and degree of differentiation.

Granulosa cell tumor

 Incidence: 1-2% of ovarian tumors
 Clinical: estrogen producing in 70% - sexual precocity, endometrial hyperplasia and carcinoma
 Gross: unilateral, solid or solid-cystic, gray to yellow, necrosis and hemorrhage
 Microscopic:
 Microfollicular pattern most common, with Call-Exner bodies (granulosa cells surrounding a
central space with eosinophilic material)
 Trabecular, solid, tubular, diffuse
 Nuclear grooves
 Prognosis: low grade malignancy; 10-yr survival rate >90%

Thecoma
 Incidence: 1/3 as common as granulosa cell tumor
 Clinical: pre- and postmenopausal; estrogenic effects more common than granulosa cell tumors
 Gross: unilateral, solid, yellow
 Microscopic: cells with vacuolated, lipid-rich cytoplasm
 Biologic behavior: benign

Fibroma
 Incidence: 4% of ovarian tumors
 Clinical: Meig’s syndrome (<1%) – ascites and hydrothorax
 Gross: unilateral, solid, white, whorled
 Microscopic: spindle cells in bundles producing collagen
 Benign

Sertoli-Leydig cell tumor (Androblastoma)
 Incidence: <0.5% of ovarian tumors
 Clinical: young (average 25 years); virilization
 Gross: unilateral; solid or solid-cystic
 Microscopic: predominantly tubular pattern (Sertoli cell component) with the stroma consisting of
fibrous tissue with Leydig cells
 Four categories: well differentiated, intermediate differentiation, poorly differentiated, with
heterologous elements
 Prognosis depends on differentiation and stage
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GERM CELL TUMORS

These tumors are derived from germ cells directly (dysgerminoma) or indirectly through embryonic
(teratoma) or extra-embryonic (EST, choriocarcinoma) differentiation.

Dysgerminoma
 Incidence: 1-2% of ovarian tumors
 Clinical: adolescent or young adult female
HCG-producing in 6-8% when associated with syncytiotrophoblastic giant cells
Radiosensitive
 Gross: unilateral (bilateral in 15%); solid; gray white
 Microscopic: (1) primitive germ cells with vesicular nuclei and prominent nucleoli; (2) delicate
fibrous strands with lymphocytes
 Prognosis: 90% 5-year survival

Endodermal sinus tumor (yolk sac tumor)

 Incidence: 1% of ovarian tumors
 Clinical: children, adolescent and young adult females
Serum AFP – diagnosis and monitoring
 Gross: unilateral, solid, gray, gelatinous, with necrosis and hemorrhage
 Microscopic: a variety of patterns – microcystic, macrocystic, solid, alveolar-glandular, papillary,
endodermal sinus
1. Schiller-Duval bodies: central capillary lined by cuboidal cells
2. Hyaline globules: PAS positive globules, source of AFP
3. Reticular pattern
 Associated lesions: teratoma, dysgerminoma, choriocarcinoma
 Prognosis
STAGE SURVIVAL
Pre-VAC VAC
All stages 5-10% 73%
Stage I 20% 92%
Stage II,III,IV 0 44%

Embryonal carcinoma
 Extremely rare, usually occurs in combination with other neoplastic germ cell elements
 Least differentiated form of germ cell tumor
 Highly malignant, locally aggressive, early metastasis

Choriocarcinoma
 May arise in the ovary in three ways:
1. As a primary gestational choriocarcinoma associated with ovarian pregnancy
2. As metastatic chorioCA from gestational chorioCA elsewhere in the genital tract
 3. As a germ cell tumor differentiating in the direction of trophoblastic structures (nongestational
chorioCA) – extremely rare

Teratoma
 A neoplasm composed of a disorganized mass of different kinds of tissues derived from three germ
layers.
1. Mature teratoma
2. Immature teratoma
3. Monodermal and highly specialized: struma ovarii, carcinoid

Mature cystic teratoma

 Most common type of ovarian teratoma
 Composed of fully differentiated mature tissues, usually ectodermal (skin, sebaceous glands, hair, glia)
but also including mesodermal and endodermal derivatives
 Complications: torsion, rupture, infection, malignant transformation (2%)

Immature teratoma
 Incidence: 1% of all ovarian cancers
 Clinical: children and young adults
 Gross: unilateral, solid, solid-cystic; necrosis and hemorrhage
 Microscopic: immature tissues derived from 3 germ layers (must be differentiated from malignant
transformation of mature tissues)
 Thorough sampling and careful examination very important
 Prognosis depends on stage and grade
 Histologic grading of Immature teratomas
Grade 0 – Mature tissues only
Grade 1 – Mainly mature but some immature tissues
Neuroepithelium limited to 1 LPF per slide
Grade 2 – Moderate amount of immature tissues
Neuroepithelium 1-3 LPF per slide
Grade 3 – Abundant immature tissue
Neuroepithelium 4 or more LPF per slide

Metastatic tumors of the ovary

Primary sites
 Stomach 38% (signet ring carcinoma)
 Colon 14%
 Breast 6-40% (average 10%)
Bilateral in 80%; solid.
Microscopic: mucin-filled signet ring cells
Routes: direct spread (f. tubes, uterus)
Transtubal (CA of corpus uteri)
Surface implantation
Progosis: most patients die within a year