This document provides information on the normal anatomy and histology of ovaries as well as pathological conditions that can affect the ovaries. It begins by describing the normal development and structure of ovaries, including the presence of ova and follicles in the cortex and blood vessels in the medulla. Various pathological entities are then discussed such as polycystic ovarian syndrome, ovarian torsion, and various types of ovarian tumors including serous, mucinous, endometrioid, clear cell, Brenner's, granulosa cell, and germ cell tumors. For each condition, the morphology, histology, clinical features, and prognosis are described. Germ cell tumors are noted to arise from abnormal gonadal development.

1. Pathology of Ovaries
Dr.CSBR.Prasad, M.D.

2. Normal ovary
Each ovary contains the ova, or primordial
germ cells, that will eventually contain a
haploid number of chromosomes. Thus,
an ovum has a karyotype of 23, X and can
be fertilized by either a 23, X or 23, Y
sperm to produce a 46, XX female or 46,
XY male offspring.

3. The fetal ovary contains mostly ova, with an indistinct intervening stroma.

4. Normal ovary
The number of follicles will begin to
decrease even before birth, and by
puberty there will only be several
hundred that remain to undergo
ovulation during reproductive years.

5. Normal ovary
• The adult ovary consists of a cortex and a medulla.
• A mesothelium, also known as the germinal epithelium, surrounds
the ovary.
• The outer cortex consists mainly of a stroma, or interstitium,
composed of small fusiform cells that can transform under hormonal
influence to support the developing ova. the cortex contains
scattered ova. A primordial follicle consists of just the oocyte
surrounded by a flattened layer of stromal cells.
• The central medullary portion of the ovary contains abundant blood
vessels in connective tissue.
• Both the ovary and the fallopian tube are supported and held in
place by a broad ligament of connective tissue with the vascular
supply.
• There are a few scattered hilus cells (the female equivalent of
testicular Leydig cells) capable of secreting androgenic steroids.

6. Normal adult ovary at low magnification reveals a dense ovarian
cortex with abundant stroma and few follicles. A developing primary
follicle with prominent granulosa cells is seen near the center. At the
lower right is a pink cloud-like corpus albicans.

7. Normal adult ovary at high magnification reveals a dense ovarian cortex
with abundant stroma and only a few follicles that contain the germ
cells--the ova. At high magnification can be seen a developing primary
ovarian follicle with a central oocyte and surrounding granulosa cells.

8. Ovulation
During reproductive years, primordial follicles are
transforming into primary follicles that have a
layer of granulosa cells to support the oocyte.
A primary follicle is surrounded by interstitial cells
termed the theca. As this structure enlarges and
fluid accumulates centrally, it becomes a
secondary follicle.
A mature follicle takes about 10 to 14 days to
develop, at which time ovulation with release of
the oocyte can take place.

9. Ovulation
After ovulation, the mature follicle that released the
oocyte becomes a corpus luteum.
If the oocyte becomes fertilized by the sperm and
implants in the endometrium, hormonal changes
transform the corpus luteum into a steroid
factory, producing much progesterone, that
maintains the pregnancy.
If fertilization does not occur, the corpus luteum
involutes into a corpus albicans that appears as
a cloud-like pink scar.

10. Normal Ovary
• At menopause the ovary loses regular
hormonal stimulation and atrophies.
• In the postmenopausal ovary, there are
no follicles, only a dense stroma
containing corpora albicantia, and a
medulla with thick, hyalinized blood
vessels.

11. The postmenopausal ovary is much smaller that the ovary of
reproductive years and contains corpora albicantia along with thick
vessels and a dense outer stroma devoid of follicles.

12. PCOD
Stein-Leventhal syndrome
• 3-6% of women in reproductive age suffer
from this.
--Persistent anovulation
--Obesity
--Hirsutism
--rarely Virilization
--Oligomenorrhea
--US shows Follicular cysts

13. Morphology:
--ovary is enlarged 2X
--grayish white with smooth surface
--thick cortex
--cortex is studded with subcortical cysts of 0.5-
1.5cms.
--hyperplasia of theca interna
--corpora lutea are frequently absent
PCOD
Stein-Leventhal syndrome

15. This MRI scan
of the pelvis in
sagittal view
demonstrates
multiple small
peripheral fluid-
filled cysts of an
enlarged ovary
consistent with
polycystic
ovary.

16. Polycystic ovarian disease (PCOD) is characterized by ovarian enlargement with
thickening of the outer cortex (at left) and many follicle cysts (one is at the right).
PCOD with oligomenorrhea is known as Stein-Leventhal syndrome. Anovulatory
cycles can be coupled with endocrine abnormalities including hirsutism. Some patients
are obese.

17. At high magnification, the thick cortex is seen, along with some scattered follicles. PCOD may
be due to pituitary dysfunction with either irregular release of LH or with hyperprolactinemia.
Treatment consists of controlling the menstrual cycle and inducing ovulation pharmacologically.

18. Torsion - ovary

19. This ovary is dark and enlarged from hemorrhage following torsion. Torsion of the ovary is
uncommon but may occur in adults in conjunction with benign ovarian cysts or neoplasms and in
children or infants spontaneously. It leads to a presentation like that of acute appendicitis, but an
adnexal mass may be palpable. The disruption of the blood supply results in hemorrhagic
infarction.

20. Parovarian cyst and ovary with torsion
VCDL 1218-06

21. Cut surface showing hemorrhages in to the wall
VCDL 1218-06

22. Ovarian tumors

23. Ovarian tumors
• They are common forms of neoplasia in
women**
• They constitute around 1-3% gynec
admissions*
• About 75% are benign - occur mostly in
young women (20-45yrs)*
• The malignant tumors - older women - 40
& 65yrs**
Source: *Text book of gynecology by D.C.Dutta 4th
Ed
**Robbins Pathologic basis of disease

24. Ovarian tumors - Classification
• WHO classification separates ovarian
neoplasms according to most probable
tissue of origin
1-Surface epitrhelial tumors
2-Germ cell tumors
3-Stromal tumors
Source: Robbins Pathologic basis of disease

25. • Nulliparity
• Family history
• Heritalbe mutations (ex: BRCA)
• High frequency in unmarried women and married
women with low parity
• Gonadal dysgenesis
• Reduced incidences – OCs and Tubectomy
• BRCA1 and BRCA2 mutations (60% & 20% by
age of 70yrs)
• ~30% ovarian adenocarcinomas express
HER2/neu oncogene – poor prognosis
• p53 mutations are seen in 50% of ovarian
carcinomas
Ovarian tumors - Pathogenesis
Source: Robbins Pathologic basis of disease

29. Serous tumors
• They account for 40% of all ovarian
cancers and is the most common malignant
tumor of the ovary
• These tumors are cystic and are filled with
clear fluid hence the name – serous
• They are lined by tube like epithelium – tall
ciliated columnar
• 75% are benign / borderline
• 25% are malignant

30. Morphology:
• Cystic lesion with smooth surface and
glistening wall
• There may be small papillary projections
• Borderline cysts may contain increased
number of papillary projections
• Mostly solid mass with irregularity and
fixation and nodularity of the capsule are
indicators of malignancy
Serous tumors

31. Microscopy:
• Lined by columnar epithelium with cilia
• Microscopic papillae
• Borderline tumors contain increasing
compelxity of papillae and stratification
of epithelium (< 4cell thickness)
• Malignant lesions are solid with cell
features of malignancy
• Psammoma bodies may be seen
Serous tumors

32. 5yr survival rate:
• Boderline 100% (ovary),
90% (peritoneum)
• Malignant 70% (ovary),
25% (peritoneum)
Serous tumors

33. Seen here in the pelvis adjacent to the uterus in the midline is a tumor of ovarian
surface epithelium--a serous cystadenoma of the right ovary. The left ovary is atropic,
consistent with a postmenopausal state. Such tumors can reach a large size because
they do not impinge upon surrounding structures until they are quite large. They may
cause some local discomfort.

34. Here is an excised serous cystadenoma. It was filled with pale yellow serous fluid in
only a single cavity. Mucinous tumors are filled with sticky mucin and tend to be
multiloculated. Benign epithelial ovarian tumors are bilateral in about 20% of cases.

35. Benign epithelial tumors of the ovary can reach massive proportions.
The serous cystadenoma seen here fills a surgical pan and dwarfs the 4
cm ruler.

37. Here is a benign serous cystadenoma that demonstrates multiloculation.
Note that the inner surface is, for the most part, smooth, with only a
solitary papillation at the upper right.

40. This is a borderline serous tumor of the ovary. This mass had a smooth surface, and
upon opening revealed the papillary appearance shown here. Such borderline tumors
are not clearly malignant, and conservatively the ovary can be resected.

41. Microscopically, a borderline serous cystadenoma is seen here with
papillary projections of epithelium extending into the lumen of the
tumor. There is no invasion of the stroma or capsule.

42. This ovarian papillary cystadenocarcinoma is mostly composed of solid tissue and has invaded
outside of the ovary, with papillations seen over the surface. Because there are no early signs or
symptoms with masses in the ovary, many of these ovarian tumors have metastasized by the time
they are detected with abdominal enlargement. These neoplasms characteristically spread by
"seeding" along peritoneal surfaces.

44. This is a papillary serous cystadenocarcinoma. Note the many papillations on the inner surface.
Between benign cystadenomas and malignant cystadenocarcinomas lies the grey zone of
"borderline" lesions that are not clearly malignant, but are treated as though they could be.

45. Here is a serous cystadenocarcinoma in which there is more pronounced
papillary growth with more hyperchromatic cells.

46. Ovarian papillary serous cystadenocarcinomas may contain small concretions called
psammomma bodies, seen here as purplish rounded and laminated objects. They are
essentially just a form of dystrophic calcification in neoplasms.

53. Mucinuos tumors
• Constitute 25% of ovarian tumors
• Middle adult life (rare before puberty
and after menoapuse)
• 15% are malignant
• Malignant tumors constitute ~10% of
ovarian cancers

54. Morphology:
• Cysts of variable sizes
• They tend to produce large cystic
masses (25kgs)
• Multiloculated tumor filled with sticky,
gelatinous fluid rich in glycoproteins
Mucinuos tumors

55. Microscopy:
• Tall columnar epithelium with apical mucin
• No cilia
• Resemble cervical or intestinal type of
epithelium
• “Mullerian mucinous cystadenoma” (arising in
endometriosis)
• Malignant tumors exhibit papilale, nuclear
atypia and stratification, necrosis et.c.
Mucinuos tumors

64. • Pseudomyxoma peritoni
-extensive mucinous ascitis
-inability to drain the ascitis
-epithelial implants on the peritoneum
-intestinal obstruction and death
Mucinuos tumors

65. Endometroid tumors
• 20% of ovarian cancers
• All are carcinomas
• Glands resembling endometrial glands
• 15% are accompanied by EM ca
• 15% co-exists with endometriosis
• Gross: cystic and solid areas
• 5yr survival is ~75%

66. Clear cell adenocarcinoma
• Uncommon
• Younger age group
• Solid or cystic
• The clear cells are arranged in sheets or
tubules
• Aggressive neoplasms

71. Brenner’s tumor
• Adenofibroma
• Transitional epithelium with fibrous
component
• They may be associated with
mucinous cystadenomas

72. • Solid and cystic
• Unilateral
• Two components – transitional
epithelium and fibrous component
• Cysts may be lined by mucinous
epithelium
• Malignant counterparts can occur
Brenner’s tumor

74. Microscopically, this benign ovarian tumor has nests of cells resembling transitional
epithelium in a fibrous stroma. This is a Brenner tumor. They can be solid or cystic,
most are unilateral, and they range from no more than a centimeter to 20 cm in size.

76. Brenner’s tumor
Bean shaped nucleus

78. Brenner’s tumor (solid areas) and mucinous tumor (cystic area)

79. Granulosa - Theca cell tumor
• Composed of varying proportion of
granulosa and theca cells
• Usually unilateral
• Solid to cystic appearances
• Hormonally active tumors appear
yellow

80. This is a granulosa cell tumor of ovary with a variegated cut surface. These tumors are derived
from the ovarian stroma and often have a component of thecoma. They are often hormonally
active and can produce large amounts of estrogen such that the patient may initially present with
bleeding from endometrial hyperplasia.

85. Granulosa cell tumor
Microscopically
• Small cuboidal to polygonal cells
• Having nulcear grooving
• Arranged in cords, sheets, strands.
• Call-Exner bodies (recall immature
follicle)
• Theca component consists of clusters of
spindle to polygonal cells with
lutenization

86. Microscopically, the granulosa cell tumor attempts to form structures that resemble
primitive follicles, as seen at the left. Most of these tumors are histologically benign,
but some are malignant.

87. At higher magnification, an ovarian granulosa cell tumor has nests of cells which are
forming primitive follicles (Call-Exner bodies).

90. Granulosa tumor
Grooved nucleus

91. Granulosa cell tumors
Clinical importance:
• They may elaborate large amounts of
estrogens
• Potentially malignant
• Juvenile granulosa cell tumors may produce
precocious puberty, EM hyperplasia, FCD of
the breast and EM carcinoma
• Marker: Inhibin (elevated levels in serum)

95. Thecoma

98. Fibroma

99. Here is an ovarian stromal tumor that is hard and white and is a fibroma.

100. This is the cut surface of a fibroma. Such neoplasms slowly enlarge
over the years.

104. Here are bilateral benign ovarian tumors. These proved to be fibrothecomas. The thecoma
component of the neoplasm gives the tumor a yellowish cast because of the lipid content and can
also produce estrogen. These are tumors that arise from the ovarian stroma. They are bilateral in
only about 10% of cases. A right-sided hydrothorax in association with this tumor is known as
Meig's syndrome.

105. Germ cell tumors

106. Germ cell tumors
Beginning with germ cells themselves,
an early conceptus matures and
consists of two parts:
1-Embryonic part (Embryo)
2-Extra embryonic part
(Trophoblast and extraembryonic mesoderm)

107. Figure 22-47 Histogenesis and interrelationships of tumors of germ cell origin.

108. Germ cell tumors
Hence germ cell tumors can be divided into:
1-Those that continue to resemble germ
cells (ex: Dysgerminoma)
2-Those that resemble protions of the
embryo (ex: Teratomas)
3-Those that resemble protions of the
extraembryonic tissue (ex: Yolk sac tumor,
Choriocarcinoma)

109. Germ cell tumors
Characteristically germ cell tumors
arise in abnormal gonads
(Dysgenetic gonads)

110. Germ cell tumors
In normal ovary:
1-Germ cells are surrounded by an epithelial
layer
2-Those which fail to have this lining will
degenerate and disappear
3-This is very important for the health of the
germ cells

111. Germ cell tumors
Dysgenetic gonad: will show one or the other
form of faulty encapsulation:
1-Germ cells lying loose in the gonadal stroma
without encapsulated by epithelium
2-Large follicles containing many germ cells,
each separately encapsulated by granulosa
cells. (This is associated with calcifications - Gonadoblastoma)

112. Teratomas

113. Here are bilateral mature cystic teratomas of the ovaries. These tumors represent one form of
ovarian germ cell tumor. A variety of mature, well-differentiated tissue elements may be found
from all three embryologic germ layers (ectoderm, mesoderm, endoderm). These tumors are
often called "dermoid cysts" because they are mostly cystic and mostly contain ectodermal
elements, typically resulting in the abundant hair seen here.

114. The cystic nature of a mature teratoma of ovary is seen here. The most common tissue element of these
teratomas is skin, so large amounts of hair and sebum are produced, leading to a challenging cleanup problem
in surgical pathology following dissection of these tumors. If these tumors are mostly solid, then they are
often "immature" teratomas with less differentiated tissue and may behave more aggressive. Rarely, there are
frankly carcinomatous areas.

115. There is a large unilateral mature cystic teratoma seen here at the right (in left ovary--
the uterus is opened anteriorly). The uterus has an intramural and a subserosal
leiomyoma. The other ovary is replaced by a fibroma.

118. Rokitansky’s protuberance

121. Microscopically, this teratoma has cartilage, adipose tissue, and intestinal glands at the
right, while at the left is a lot of thyroid tissue. This condition can be termed struma
ovarii. Rarely, a struma ovarii can even be a cause for hyperthyroidism.

123. Carcinoid tumor

126. Struma ovary

129. Dysgerminoma
• Relatively uncommon tumors
• 2% of all ovarian cancers yet form about half of
malignant germ cell tumors.
• They may occur in childhood, but 75% occur in
the second and third decades.
• patients with gonadal dysgenesis, including
pseudohermaphroditism.
• Most of these tumors are nonfunctional. A few
produce elevated levels of HCG
• Radiosensitive

131. This is an ovarian dysgerminoma that has been sectioned into two halves. Note
the pale brown appearance of the parenchyma, along with some central
collagenous scar. The gross and microscopic appearance of an ovarian
dysgerminoma is essentially the same as a seminoma of the testis in a male.

132. This is another ovarian dysgerminoma that on sectioning reveals a lobulated tan
appearance. Some normal edematous light brown ovarian tissue is present at the right.
Such tumors are usually solid. Only 10 to 20% are bilateral. They occur most often in
young women.

136. Metastatic deposits
• The most common "metastatic" tumors of
the ovary are probably derived from
tumors of müllerian origin: the uterus,
fallopian tube, contralateral ovary, or
pelvic peritoneum.
• The most common extramüllerian
primaries are the breast and
gastrointestinal tract, including colon,
stomach, biliary tract, and pancreas.

138. "Krukenberg" tumor of ovary which has a signet ring histologic pattern and usually is metastatic
from a primary in gastrointestinal tract. Seen here extending out of the pelvis at autopsy is a large
right ovarian mass. Metastases are also present in the lower right portion of liver.
Ovarian mass
Liver

140. Presence of intracellular mucin
evidenced by Meyer’s mucicarmine stain

141. Can you identify this metastatic tumor ?
Lobular carcinoma of the breast. There is prominent Indian filing.

142. E N DE N D
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