Ovaries and Ovarian Tumours

1. Dr. Saumya, Dept of Pathology, SIMS
www.shadan.in

2. NORMAL OVARIES
 Normal size 5 x 3 x 3cm
 Variation in dimensions can result from
 Endogenous hormonal production(varies with age and
menstrual cycle)
 Exogenous substances, including OCs, GnRH agonists, or
ovulation-inducing medication, may affect size

4. Lifetime Risk of ovarian neoplasm
 A woman has 5–10% lifetime risk of undergoing surgery
for a suspected ovarian neoplasm and
 13–21% of these will be found to be have an ovarian
malignancy

5.  Differential diagnosis of the adnexal masses varies considerably with
the age of the patients.
 In pre-menarchal girls and post-menopausal women adnexal mass
should be considered highly abnormal – requires immediate
investigation.
 In menstruating patients differential diagnosis is varied.

6. Clinical features:
1. Pelvic pain
2. Menstrual irregularities ( abnormal pattern of
ovarian hormone secretion).
3. Infertility; failure of ovulation (Stein-Leventhal).
4. Ovarian mass : either non-neoplastic (cysts) or
neoplastic (cystic or solid).

7. DIAGNOSTIC EVALUATION OF THE PATIENT WITH AN
ADNEXAL MASS
 Complete physical examination
 Pelvic ultrasound examination
 Computed tomography scan with contrast enhancement or
intravenous pyelography
 Colonoscopy or barium enema study, if symptomatic
 Laparoscopy, laparotomy

8. OVARIAN
MASSES
FUNCTIONAL INFLAMMATORY NEOPLASTIC OTHERS
FOLLICULAR CYST
CORPUS LUTEUM
CYST
THECA LUTEIN
TUBO OVARIAN ABSCESS BENIGN
BORDERLINE
MALIGNANT
ENDOMETRIOMA
ENLARGED PCO
PAROVARIAN CYST

9. COMMON OVARIAN TUMOURS
Infancy Pre pubertal Adolescent Reproductive Peri
Menopausal
Post
Menopausal
1 Functional
cyst
Functional
cyst
Functional
cyst
Functional
cyst
Epithelial
ovarian
tumor
Neoplastic
ovarian
tumor
2. Germ cell
tumor
Germ cell
tumor
Germ cell
tumor
Dermoid Functional
cyst
Functional
cyst
3. Epithelial
tumor
Epithelial
tumor
Mets

10. Functional ovarian cysts
 Follicular cysts
 Corpus luteum cysts
 Theca lutein cysts
 Luteomas of pregnancy
By far the most common clinically detectable enlargements
of the ovary in the reproductive years.
All are benign and usually asymptomatic.

11. Follicular cysts
 Cystic follicle is defined as Follicular cyst of diameter > 3cm
 Most common functional cysts.
 Rarely larger than 8cm.
 Lined by granulosa cells
 Found incidentally on pelvic examination
 Usually resolve within 4 – 8 weeks with expectant management
 May rupture or torse occasionally causing pain and peritoneal
symptoms.

12. Follicular cysts

15. Corpus luteal cyst
 Less common than follicular cyst.
 May rupture leading to hemoperitoneum and requiring surgical
management( more in patients taking anti coagulants or with
bleeding diathesis)
 Unruptured cysts may cause pain because of bleeding into
enclosed ovarian cyst cavity.

16. Corpus luteal cyst

19. Theca lutein cysts
 Least common
 Usually bilateral
 Result from overstimulation of the ovary by β- hCG
 Do not commonly occur in normal pregnancy
 Often associated with hydatidiform moles, choriocarcinoma,
multiple gestations, use of clomiphene and GnRH analogues.
 May be quite large (up to 30 cm) , multicystic, and regress
spontaneously.

20. Theca lutein cysts

21. Polycystic ovarian (Stein-Leventhal
syndrome(PCOD)
 It is important cause of infertility. There is excessive
production of androgens, increase conversion of androgens to
estrogen, insulin resistance, and inappropriate gonadotrophin
production by the pituitary.
 Morphology: Ovaries are large, white, many subcortical
follicular cysts(0.5-1 cm.) in diameter, and covered by
thickened fibrosed outer tunica. No corpora lutea (= no
ovulation).
 Manifestations: Young females with Oligomenorrhea,
infertility, obesity & hirsuitism.

22. Polycystic ovary

23. Endometriosis (chocolate cyst)
 Most common site of involvement is the ovary.
 Endometriomas are pseudocysts formed by invagination of the ovarian
cortex, sealed off by adhesions.
 They may completely replace normal ovarian tissue. Cyst walls are usually
thick and fibrotic.
 USG: anechoic cysts to cysts with diffuse low-level echoes to solid-
appearing masses.
Fluid–fluid or debris–fluid levels may also be seen.
They may be unilocular or multilocular with thin or thick septations
 Malignant transformation: 0.3% to 0.8%
 Management: medical and/ or surgical

26. Management of functional cysts
 Expectant
 Watchful waiting for two or three cycles is appropriate.
 Combined oral contraceptives appear to be of no benefit.
 Should cysts persist, surgical management is often
indicated.
Oral contraceptives for functional ovarian cysts (Review)
Cochrane Database of Systematic Reviews 2011

28. OVARIAN TUMORS
- Common forms of neoplasia in women.
- 80-90% of ovarian tumors are benign.
- Most ovarian tumors occur between 20-45 years.
- Ovarian cancer is second MC malignancy of the female
genital tract (after endometrial cancer).
- Most ovarian tumors are derived from surface epithelium,
and “CA-125” is the tumor marker for surface epithelial
tumors of the ovary.
- Malignant ovarian tumors present at a late stage, thus are
associated with high mortality rate.
- Known risk factors are nulliparity, family history, and
specific inherited mutations (BRCAI & BRCAII) genes.

29. Precursor Ovarian component Other female genital tract
structures
Coelomic epithelium
Ectopic endometrial
epithelium—Mullerian
Epithelium
Surface epithelium 1.Fallopian tubes( ciliated
columnar serous cells)
2.Endometrial lining(non
ciliated columnar cells)
3. Endocervical glands
(mucinous non ciliated)
Yolk Sac Germ cells(toti potent)
Sex cords Stroma of the ovary Endocrine apparatus of post
natal ovary.

31. Tumour types-- a basic classification
Site of origin Types Frequency Age group
Surface epithelial
tumours
1.Serous
2.Mucinous
3.Endometroid
4.Clear cell
5.Brenner
60%-70% 20 years and greater
Germ cell 1.Teratoma
2.Dysgerminoma
3.Endodermal Sinus(Yolk Sac
Tumour)
4.Choriocarcinoma
15%-20% 0 to 25 years and
greater
Sex cord stromal
tumours
1.Granulosa Theca cell
tumours
2.Sertoli-Leydig cell tumours
3.Gynandroblastoma
5%-10% All ages
Miscellaneous 1.Lipid cell tumour
2.Gonadoblastoma
Variable variable
Metastasis Krukenberg tumours 5% variable

34. III. SEX CORD-STROMAL TUMORS:
1- Granulosa-Theca cell tumor: secrete
estrogen
2- Sertoli-Leydig cell tumor: secrete androgens
3- Fibroma: associated with Meig’s syndrome
4- Sex cord stromal tumor with annual tubules
5- Gynandroblastoma
6- Steroid (Lipid)cell tumors

36. I. Surface mullerian epithelial tumors: (Benign,
Borderline, and Malignant)
1-Serous tumors: composed of ciliated columnar (tubal
type) epithelium
2- Mucinous tumors: composed of mucus-secreting
(cervical canal type) epithelium
3- Endometrioid tumors: composed of glandular
(endometrium-like) epithelium.
4- Brenner’s tumors: composed of transitional
(urothelium-like) epithelium
5- Clear cell tumors.

37. Serous tumors
Cysts are lined by tall columnar, ciliated epithelial cells (fallopian tube type)
& filled with serous fluid.
Types:
 Benign Serous Tumors (Cystadenomas): (60%),
smooth lining & no papillary or solid areas. 20% are bilateral.
 Borderline Serous Tumors (low malignant potential): (15%),
epithelial atypia, solid areas, but no stromal invasion. 30% are bilateral.
 Malignant Serous Tumors (Cystadenocarcinomas): (25%)
multilayered epithelium, solid areas & papillary structures
invasing the stroma. 65% are bilateral. The prognosis depends on
stage, and the presence of peritoneal implants means poor prognosis.

38. Serous cystadenomas
 Benign tumors typically have a smooth glistening cyst
wall with no epithelial thickening or with small papillary
projections.
 Microscopy : the cysts are lined by columnar epithelium,
which has abundant cilia in benign tumors. Microscopic
papillae may be found

42. Borderline serous tumours
 Borderline tumors contain an increased number of
papillary projections
 Exhibit increased complexity of the stromal papillae –
hierarchical pattern, stratification of the epithelium and
mild nuclear atypia, but invasion of the stroma is not seen
or there is stromal microinvasion (< 1cm).

43. Borderline serous tumours

44. Stromal
microinvasion

45. Serous carcinoma
 Serous carcinoma are classified into 2 subtype
 low-grade serous carcinoma (LGSC)
 High-grade serous carcinoma(HGSC)
 These tumors are different based on their molecular study.

46. Pathogenesis

47. APST - Atypical proliferative serous tumour
SBT – Serous borderline tumour

48. Spread of STIC from the Fimbria to the Ovarian Surface

49. Development of Cortical Inclusion Cyst from Tubal Epithelium

53. HGSC
• Most common ovarian carcinomas.
• High stage disease at the time of presentation.
• Histopathology:
– Highly stratified epithelium with a fenestrated appearance
and slit-like spaces, with/without solid or microcystic
growth.
– The tumor cells are of intermediate size, with scattered
bizarre mononuclear giant cells, prominent nucleoli, and
high mitotic rate.
– >3 fold variation in nuclear size, and mitosis >12/10HPF
distinguishes HGSC from LGSC.

61. LGSC
• Uncommon tumor(<5%) with excellent prognosis due
to its indolent course and delayed recurrence.
• Histopathology:
– Uniform nuclei and differentiated architecture with
papillary growth;
– Numerous psammoma bodies.
– The uniformity of the nuclei with <3 fold variation, is the
principal criterion for distinguishing between LGSC and
HGSC.
– LGSC is considered microinvasive if invasive foci measures
<10mm2.

62. • Molecular genetics:
– BRAF mutation
– KRAS mutation
– Unlike HGSC, no BRCA germline mutation, no
chromosomal instability.
• Therapy:
– Surgical excision.
– Unlike HGSC, it is Less sensitive for platinum based
chemotherapy.

63. Low grade ovarian serous
carcinoma with a micropapillary
pattern
Transition between borderline
serous cystadenoma and
invasive low grade serous
carcinoma.

69. Mucinous carcinoma
 Arise from transitional epithelial nests in paraovarian locations at
the tubo-peritoneal junction.
 Histopathology:
 Heterogeneous group of tumors.
 Benign-appearing, borderline, intraepithelial carcinoma, and
invasive patterns may coexist within an individual neoplasm
 Mucinous borderline tumor with intraepithelial carcinoma is
used for those tumors that lack the architectural features of
carcinoma but show cytological features of malignancy.

70. Large cystic masses, huge size, unilateral and multiloculated. Cysts filled with
sticky gelatinous fluid. They either lined by tall columnar mucus-secreting (rich
in glycoprotein) epithelium (intestinal-type mucinous cystomas) or show
papillary architectures and focal cilia (mullerian mucinous tumors), which may
be associated with endometriosis.
1- Benign Mucinous Tumors (cystadenomas):
80%; large cysts with smooth lining & no atypia. 5% are bilateral.
2- Borderline Mucinous Tumors (of low malignant potential):
10-15%; cellular atypia, but no stromal invasion.
3- Malignant Mucinous Tumors (Cystadenocarcinomas):
5-10%; atypia, solid sheets & stromal invasion.
20% bilateral.
Seeding in the peritoneum with malignant deposits causes
pseudomyxoma peritonei.
Usually mucinous cystadenocarcinomas are of intestinal type.

71.  Pseudomyxoma peritonei is marked by extensive
mucinous ascites, cystic epithelial implants on the
peritoneal surfaces, adhesions, and frequent involvement
of the ovaries.
 Pseudomyxoma peritonei, if extensive, may result in
intestinal obstruction and death

75. Borderline mucinous cystadenoma-ovary

76. Borderline mucinous cystadenoma

77. Mucinous cystadenocarcinoma

82. • 20% of all ovarian tumours.
• Majority are carcinomas, if benign forms are present they
are cyst adenofibromas.
• Distinguished from serous and mucinous tumours by
presence of tubular glands bearing close resemblance to
benign or malignant endometrial glands.
• 30% associated with carcinoma endometrium and
15% with endometriosis whereas 40% involve both
ovaries.
Endometriod carcinoma

83.  Gross: presence of both solid
and cystic areas
 Microscopic: Tubular
glands resemble those of
typical endometrial
adenocarcinoma.

84. Clear cell tumour
 These are uncommon and aggressive tumours.
 Grossly can present in solid and or cystic pattern (solid
tumour with cysts and necrosis)
 Microscopically: large epithelial cells with abundant clear
cytoplasm.

86. Brenner tumour
 Uncommon adenofibromas
 Epithelial components– nests of transitional cells
resembling urinary bladder.
 Most are benign,variable size(1cm to 30 cm).
 Gross—solid or cystic
 Microscopic – fibrous stroma resembling normal ovarian
stroma seperated by sharply demarcated nests of urinary
tract, with mucinous glands.

87. Brenner tumour
 Gross:A sharply
demarcated, yellow-white
fibromatous tumor
occupies a portion of the
sectioned surface of the
ovary.
Microscopically:Nests of
transitional cells, some
containing cysts, lie in a
fibromatous stroma.

88. II. GERM CELL TUMORS:
1- Teratoma
2- Dysgerminoma (seminoma ovarii)
3- Yolk sac tumor= Endodermal sinus tumor
4- Embryonal carcinoma (MC mixed with other
types)
5- Choriocarcinoma (MC mixed with other types)

89. Germ cell tumors
15-20% of all ovarian tumors. It arises from
totipotent germ cells capable of differentiation into the
three germ layers.
- Mostly benign cystic teratomas while Other
tumours are found principally in children
and young adults.
- Homologous to germ cell tumours in male testis.

90. Histogenesis

91. TERATOMAS
Mature
Benign
teratomas
Immature
Malignant
Monodermal
or highly
specialized

92. Mature (Benign) Teratoma: MC germ cell tumors of the ovary,
cystic (dermoid cysts), lined by skin & hairs, and filled with
sebaceous secretion. There may be mature cartilage, bone
(teeth) & other structures. 10-15% are bilateral. < 1%
undergo malignant transformation (MC sq.c.c.).
Immature (Malignant) Teratoma: Rare , solid, bulky, with areas
of hemorrhage and necrosis. It contains embryonic elements
of he three germ layers. Age: adolescent & young women.
Grading is based on the amount of immature
neuroepithelium. It causes wide spread extraovarian
metatases depending on the degree of the immaturity of the
including tissues.
Monodermal (Specialized )Teratomas: differentiate along the
line of single tissue. Examples:- Strauma ovarii is MC (mature
thyroid tissue) – Carcinoid tumor.

93. MATURE CYSTIC
GROSS: unilocular cysts with hair
and cheesy material. Thin walled
gray white wrinkled epidermis.hair,
tooth and calcification are found
within walls.
TERATOMA
MICROSCOPIC: cyst wall stratified
squamous epithelium and underlying
sebaceous,sweat glands and other
adnexa.other structures like thyroid
tissue,cartilage bone may be seen.

98. Dysgerminoma
The ovarian counterpart of testicular seminoma.
 Gross- Yellowish white to gray pink solid, fleshy
tumors, of children & young adults. 10% are bilateral.
 Microscopy: sheets of large cells, separated by fibrous
stroma infiltrated by small lymphocytes. Non-functional,
but may be mixed with other germ cell elements that
produce hCG
 Malignant, but radiosensitive & chemosensitive, with
relative good prognosis if treated early.

99.  GROSS: Small nodules to
very large size.Cut surface:
yellow white to gray pink
appearance and are soft and
fleshy.
 Microscopic:large vesicular
cells, clear cytoplasm and well
defined boundaries and centrally
placed regular nuclei.cells in
sheets or cords seperated by
scant fibrous stroma, which has
mature lymphocytes.

102. Endodermal Sinus Tumor ( Yolk Sac
Tumor)= Infantile embryonal carcinoma
It arises from mutlipotent embryonal carcinoma cells
differentiating towards yolk sac structures.
- Affects children & adolescents; grows rapidly & spreads
widely, but is radio- & chemosensitive.
- Histologically: it shows cystic spaces into which papillary
structures with central blood vessels, the cyst spaces and
papillary structures are lined by immature epithelium giving
glomeruloid or “Schiller-Duval” bodies; There are intracellular
and extracellular hyaline droplet (characteristic feature). Tumor
cells are positive for Alpha-fetoprotein (tumor marker).

103. Schiller Duval Bodies

104. Choriocacinoma
It is due to teratogenous development of germ cells.
Most cases exist in combination with other germ cell tumors.
- Resembles gestational choriocarcinoma, highly malignant,
spreads widely & elaborates hCG (tumor marker).
- Microscopic picture: malignat syncitiotrophoblasts &
cytotrophoblasts in a hemorrhagic stroma.
Gonadal choriocarcinomas are more resistant to chemotherapy
than Gestational choriocarcinomas.

105. III. SEX CORD-STROMAL TUMORS:
 1- Granulosa-Theca cell tumor: secrete
estrogen
 2- Sertoli-Leydig cell tumor: secrete androgens
 3- Fibroma: associated with Meig’s syndrome
 4- Sex cord stromal tumor with annual tubules
 5- Gynandroblastoma
 6- Steroid (Lipid)cell tumors

106. Granulosa - theca cell tumor
 1- 5% of all ovarian tumors, of peri & post-menopausal
women.
- Usually unilateral, solid white yellow, consisting of
theca cells & granulosa cells, arranged in “Call-Exner”
rosettes.
- Elaborated large amount of estrogen & may cause
precocious sexual development in children, endometrial
hyperplasia, cystic changes of the breast or endometrial
carcinoma (estrogen effects).
- Pure granulosa cell tumors are potentially malignant,
clinical malignancy occurs in 5-25% of cases, but they
are slowly growing & 10-years survival is above 85%.
- Pure Theca cell Tumors - THECOMA

107.  Gross: small partly solid,
partly cystic and mostly
unilateral.The neoplasm
composed of yellow-white
tissue with hemorrhage,
some of which is
intracystic

108.  Microscopically:
granulosa cell arranged in
various patterns like
micro,macro follicular,
trabecular,bands and
sheets.CALL-EXNER
BODIES characterstic
rosette like structures
having central rounded
pink mass surrounded by
granulosa

111.  Pure thecoma are almost always benign.
 Occur in post menopausal women.
 Oestrogen dominant tumours– endometrial disorders ,
carcinoma and cystic disease of breast.
 If androgen secreting – virilizing effects.
Thecoma

112.  Gross: a solid firm mass upto
10 cm in diameter.Section
shows. solid, lobulated,
yellow tissue.

113.  Microscopically : spindle
shaped theca cells along
with variable amount of
hyalinized collagen,
cytoplasm of these cells is
vacuolated and lipid laden.

114. SERTOLI-LEYDIG CELL TUMORS
(Androblastoma= Arrhenoblastoma= Hilus Cell
Tumors = Gonadoblastomas)
 Androgen producing neoplasm (rarely produce estrogen)
 Recapitulate the testicular counterpart & produce
masculinization or defemenization (Androgen) effect.
 Usually unilateral & benign.
 Gross: cut surface is solid and colour gray to golden brown.
 Microscopic picture: Tubules lined with Sertoli cells and Leydig cells
interspersed in the stroma.
Gynandroblastoma: Extremely rare. It consists of a mixture of granulosa/theca
& sertoli/ leydig cells. It may be benign or malignant.

115. Sertoli Leydig Cell Tumor-Ovary

116.  Common ovarian tumours. Usually bilateral
 Hormonally inactive
 Meig’s syndrome: fibroma with pleural effusion and
benign ascites.
 Gross large firm fibrous usually bi-lateral mass.
 Microscopic composed of spindle shaped well
differentiated fibroblasts and collagen.
 Fibrothecoma: combination of fibroma and thecoma.
Fibroma

118. Krukenberg tumor
Metastatic tumors
• Very common,
• The primary tumors is from abdominal and breast
tumors.
 A bilateral metastatic ovarian carcinoma, composed of mucin-
producing signet ring cells, metastasizing from GIT, mostly
from the stomach, it may produce pseudomyxoma peritonei
like well differentiated appendicial tumors.