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PATHOLOGY OF OVARIES
Ansari P. Salpin, MD, DPSP
March 22, 2016
OUTLINE
I.
II.
III.
Difference: Size
For uniformity sake, the cut off is 2 cm.
If the size the size of the cyst is >2 cm, we call it
follicular cyst. If it is <2 cm then we call it cystic
follicle.
Gross: Unilocular cyst with smooth external surface
So, when a patient presents with a unilocular
cyst with a clear serous fluid, the differential
diagnosis would always be a follicular cyst or a
serous cystadenoma. So you must perform
microscopic examination to differentiate
between the two.
Microscopic:
o Granulosa cells have uniform, round nuclei and
little cytoplasm
o Thecal cells are small and spindle shaped
Corpus Luteum cyst (corpora lutea)
o Bright yellow in color
o You can diagnose it just by gross examination of
the
ovary
even without microscopic
examination because it is a bright yellow color
with a central hemorrhagic area
o Lined by luteinized theca and granulosa cells on
microscopic examination
Luteinized:
abundant
eosinophilic
cytoplasm
o Clinical significance: when they enlarge and
they rupture, they cause hemoperitoneum
Follicular Cyst
Microscopic:
o Numerous follicles in early developmental
stages
o Follicular atresia
o Increased stroma with occasional hyperthecosis
o Features of anovulation (thick, smooth capsule
and absence of corpus luteum)
Stromal hyperthecosis
o Also called cortical stromal hyperplasia
o Disorder of ovarian stroma seen in
postmenopausal women, but may overlap with
PCOS in younger women
o Uniform enlargement of the ovary (up to 7 cm)
o White to tan appearance on sectioning
o Bilateral involvement
o Microscopic:
hypercellular
stroma
and
luteinization of the stromal cells, which are
visible as discrete nests of cells with vacuolated
cytoplasm
o Clinical presentation: similar to those of PCOS;
virilization may be more striking
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Pathogenesis:
Previous theory : Arise from the mesothelial
layer of the ovary
Current theory: epithelial tumors do not come
from the ovary, they come from the fallopian
tubes from the endometrium
The fallopian tubes, however, arise from
the Mllerian ducts, which in turn is from
the mesothelium of the coelomic cavity in
which the ovaries arise from.
Studies conducted on the lining of the fallopian
tube: it contains p53 mutation
When they examined serous cell adenoma,
serous cell adenocarcinoma: they also have p53
mutations
So they propose that because of retrograde
menstruation, the endometrial cells were
implanted on the ovaries and undergo mutation
especially KRAS mutation
Another set of implicated genes are defects in
the repair genes BRCA1 and BRCA2, which is
also seen in breast cancers.
The invasion must be at least 1 cm. Some
authors, for serous tumors, consider a
malignant diagnosis if it is more than 0.5 mm
but for uniformity sake we will use 1 sq. mm.
Classified according to the type of cells. In order of
decreasing frequency, the common epithelial
tumors are:
SEROUS: looks like tubal epithelium, looks
like fallopian tube (simple ciliated columnar
epithelium)
MUCINOUS: looks like endocervical glands
or intestinal glands, easy to recognize with
basally located nuclei, clear cytoplasm
Intestinal type has poorer prognosis
compared to endocervical type
Differentiate by means of looking for
goblet cells (intestinal type has goblet
cells)
ENDOMETRIOID: looks like endometrial
cells
CLEAR CELL: has glycogen-rich cells like
endometrial glands in pregnancy
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Most
Frequent
Mutations
Chromosomal
Instability
LG serous CA
APST, noninvasive
MPSC
KRAS, BRAF
Low
LG endometrioid CA
Endometriosis
CTNNB1,
PTEN
Low
Clear cell CA
Endometriosis
PIK3CA
Low
Mucinous CA
APMT
KRAS
Low
HG serous CA
TP53
High
HG endometrioid CA
TP53
High
Undifferentiated CA
Carcinosarcoma
TP53
TYPE 1 TUMORS
TYPE 2 TUMORS
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Microscopic Findings
Simple architecture, non-branching papillae if
present with rare to absent finding
Single, orderly layer of nonstratified, cuboidal to
columnar epithelium, often ciliated
Nuclear atypia minimal or absent
The nuclei are oriented perpendicular to the long
axis of the columnar epithelium.
Borderline serous tumor of the ovary. Papillations are seen, but with
no invasion of the stroma (blue line). Some papillations grow off of a
fibrovascular core (
), which can also be seen in other
cystadenomas.
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>75%
Psamomma bodies
Psammomatous serous carcinoma
Better prognosis compared to the
usual serous CA
2. MUCINOUS TUMORS
Surface of the ovary is rarely involved
Mostly unilateral
Tend to produce larger cystic masses (up to
more than 25 kg)
Multiloculated tumors filled with sticky,
gelatinous fluid rich in glycoproteins
A. Mucinous Cystadenoma
Benign surface epithelium tumor composed
of endocervical type or intestinal type
mucinous epithelium
Basally oriented nuclei with clear cytoplasm
Most common mucinous ovarian tumor
(80%)
Unilateral
When you see a bilateral mucinous tumor, then
its not primary ovarian, its a metastasis
Gross Findings
Unilocular or multilocular
Usually mulitloculated, and can present
with hundreds of small cysts
Contains gelatinous material
Often very large (>30cm)
Size is not an indicator for malignancy
Largest tumor of the female reproductive
tract whether benign or malignant
Smooth capsule and cyst lining
Microscopic Findings
Columnar
pale
staining
mucinous
epithelium resembling endocervix or
intestine
Minimal or absent atypia
Minimal or absent stratification
If with atypia and stratification, the diagnosis
will be borderline. But atypia and stratification
must be 10% to qualify as borderline serous or
mucinous tumor.
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C. Mucinous Adenocarcinoma
Surface epithelial tumor with cytologically
malignant mucinous epithelium associated
with stromal invasion
Uncommon surface epithelial carcinoma
Unilateral
With stromal invasion of more than 10 mm2
If less than 10 mm2, label it as borderline
tumor with microinvasion
Mucinous adenocarcinoma is almost always
well differentiated. We rarely see poorly
undifferentiated.
A poorly differentiated adenoCA may be a
metastasis rather than primary ovarian tumor.
Clinical features
Asymptomatic
Abdominal enlargement
Pain
Change in bowel or bladder function
CA-125 may not be markedly elevated
Molecular Studies
KRAS mutation
No association with BRCA1 or BRCA2
mutation
(compare
with
serous
cystadenocarcinoma)
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without
Molecular study
Genetic alterations similar to endometrial
endometrioid carcinoma
o Somatic mutations in b-catenin and PTEN
o Microsatellite instability
o Germline mutation in DNA mismatch repair
associated with Lynch syndrome
Gross Findings
Cystic and solid with areas of hemorrhage and
necrosis
Bilaterality usually implies extension of the
neoplasm beyond the genital tract.
Microscopic Findings
Round to elongated glands with or without
squamous differentiation infiltrating the ovarian
stroma
Serous vs endometrioid in grade 3 tumors:
difficult to differentiate because they are both
solid, unlike mucinous which is only grade 1 or
2; high grade tumors favour serous.
Differentiation vs serous tumor:
More likely to be serous if there is/are:
1. Psamomma bodies
2. Slit-like lumen
More likely to be endometrioid if there is/are:
1. Squamous differentiation
2. Punched-out glands
3. Adenofibromatous pattern
fibrovascular core
Gross Findings
Thick walled unilocular cystic and solid mass
with fleshy nodules
Hemorrhage and necrosis on inner cyst wall and
adhesions over the capsule
May present as single fleshy nodule in an
endometriotic cyst (25%)
Micrscopic Findings
2 possible patterns:
o In solid neoplasms, the clear cells are
arranged in sheets or tubules
o Cystic neoplasms have the cell line the
cystic spaces.
Tubulocystic, papillary and solid architecture
Polyhedral cells with abundant clear and
eosinophilic granular cytoplasm
Containing 1 antitrypsin (seen in yolk sac
tumor, rhabdomyosarcoma)
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Clear Cell Adenocarcinoma. The clear cells are polyhedral and have
eccentric, hyperchromatic nuclei without prominent nucleoli
Microscopic Findings
Well circumscribed solid and cystic areas with
nests of uniform transitional epithelium
embedded in an abundant, fibromatous stroma
Not a sign of invasion because you do not
have dysmoplastic reaction.
Malignant equivalent: malignant Brenner
tumor, malignant transitional carcinoma
Dystrophic calcification (50%)
Ovoid cells with discernable grooves and small
indistinct nucleoli (nuclear grooves hallmark,
but not exclusive)
Coffee bean like nuclei
Associated with mucinous and serous
cystadenoma and dermoid cyst (25%)
Some of the nuclei can contain grooves
4. BRENNER TUMOR
A form of cystadenofibroma
Benign surface epithelial tumor composed of
urothelium (in a fibromatous stroma)
Frequently asymptomatic
Gross Findings
Well circumscribed, solid with smooth external
surface from 220cm
Sometimes with cystic component
Yellow or white tissue with small cyst and gritty
on cut section
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4. SERTOLI-LEYDIG TUMOR
Aka ANDROBLASTOMA or ARRHENOBLASTOMA
It can be a Sertoli tumor or a Leydig tumor only.
Combination of both is usually malignant.
In Sertoli tumor you have to do special stains
and when if you do electron microscope you will
see Charcott-Butcher microfilaments. This is the
hallmark of Sertoli tumor.
In contrast to the Leydig tumor, you have to
stain with crystalloids or crystals to diagnose
Leydig tumor.
Gross Findings
Average size: 1.5cm
Solid, lobulated, tan to yellow cut surface
Purely Leydig: golden brown [benign course]
Leydig produces Testosterone and occasionally
estrogen
Microscopic Findings
Sertoli-Leydig tumors are graded based on the
immature tubules
Well differentiated tubules composed of
Sertoli cells or Leydig cells interspersed in a
fibroma-thecomatous stroma
Look for the Leydig component because they are
stromal cells, cuboidal or polygonal
Intermediate outlines of immature tubules
and large eosinophilic Leydig cells
Poorly differentiated sarcomatous pattern
with disorderly diposition of epithelial cords
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1. DYSGERMINOMA
The ovarian counterpart of testicular seminoma
Least differentiated from all the other tumors
Has a good prognosis because it is chemo- and
radiosensitive compared to the other tumors
Malignant germ cell tumor resembling
primordial germ cells, morphologically identical
to seminoma and extragonadal germinoma
Most common malignant germ cell tumor
Most common in 2nd to 3rd decade
Rapidly growing mass
Elevated serum LDH and PLAP
LDH is non-specific. It is elevated on most
malignant neoplasms that are rapidly growing.
PLAP(placenta-like alkaline phosphatase)
specific marker for germ cell tumors
PLAP is also not specific for dysgerminoma since
it is elevated on all germ cell tumors.
Rarely, elevated -HCG [due to presence of
syncytiotrophoblast]
Normal AFP
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Microscopic
Arranged in nests and sheets
Separated by fibrovascular septa with
lymphoplasmocytic infiltrates or granulomas.
Although the lymphopalsmocytic infiltrates and
granulomas are not neoplastic, these are clues
to the diagnosis.
Composed of large, vesicular cells with clear
(glycogen-filled) cytoplasm, well-defined cell
boundaries, and irregularly flattened central
nuclei.
Brisk mitotic activity
2. EMBRYONAL CARCINOMA
Arise from the undifferentiated, totipotential
germ cell
Often, young women who only present with
abdominal or pelvic mass
Primitive germ cell tumor morphologically
identical to its counterpart in the testis, capable
of somatic and extraembryonal differentiation
AFP normal to slightly elevated
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Embryonal carcinoma.
3. CHORIOCARCINOMA
Most aggressive
Maybe gestational (metastasis or associated
with pregnancy) or nongestational (no chorionic
villi)
Gross Findings
Large hemorrhagic mass
Microscopic Findings
Syncytiotrophoblasts growing nests or sheets of
cytotrophoblasts in a plexiform pattern
Brisk mitotic activity in cytotrophoblasts
Extensive hemorrhage and necrosis
Vascular invasion common
Primary metastasis route: hematogenous
Chorionic villi absent
(+) chorionic villi= invasive
Worst prognosis among germ cell tumors
More common in the endometrium than in the
ovary
4. YOLK SAC TUMOR
Aka Endodermal sinus tumor
Most common malignant tumor in children
Malignant germ cell tumor showing extraembryonic differentiation, less commonly,
embryonic differentiation
Second most common malignant germ cell
tumor
Children and young females
Rapidly growing mass
Elevated AFP
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6. IMMATURE TERATOMA
Heterogenous;, may also have mature
component; immature component are in the
solid areas
Differentiate between immature component
and malignant component
Immature: chrondrocytes, enlarged nuclei
Germ cell tumor showing variable amounts of
immature tissues associated with mature
elements
More common in first two decades
Gross Findings
Large tumor with ruptured capsule in
approximately 50%
Solid, soft and fleshy cut section, often with
cystic component
Solid in contrast to mature cystic teratoma,
which are cystic
Dermoid cyst identified in 1/4 of tumors and in
the opposite ovary in 10%
Microscopic findings
Tissues from the three germ cell layers with a
variable admixture of immature and mature
elements
Amount
of
immature
epithelium
[neuroectoderm or neuroepithelium] used in
grading
o Grade 1 1 LPF in any one slide
o Grade 2 1-3 LPF in any one slide
o Grade 3 - >3 LPF in any one slide
The immature epithelium is responsible for the
behavior of the tumor; if numerous
extraovarian sequence
Neuroepithelium may look like a gland,
differentiate by looking at the background; if
fibrillary then it is neuroepithelium
The number or amount of neuroepithelium
is responsible for the prognosis of immature
teratoma.
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Krukenberg tumor. (A) The ovary is enlarged and the cut surface
appears solid, pale-yellow, and partially hemorrhagic. (B) A
microscopic section of A reveals mucinous (signet-ring) cells (clear
cells, arrows) infiltrating the ovarian stroma.
References:
Clinicopathologic
th
Foundations of Medicine, 7 ed.
Robbins and Cotran Atlas of Pathology, 3rd ed.
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