NEOPLASTIC DISEASES OF

THE OVARY
MARLA A. LLANTO, MD
Epidemiology

• 27% of gynecologic cancers

• 53% of all gynecologic cancer deaths
• most common cause of gynecologic mortality
• 5th most frequently occurring fatal cancer in women in the
US
• Will develop in approximately 14 of 1000 women in the US
older the 40
RISK FACTORS

Family history

Ethnicity

Reproduction
Risk Factors
• Family History
• The strongest risk factor
• A woman with a single first- degree relative with ovarian cancer has a
relative risk of approx. 3.6 of developing ovarian cancer than the general
population
• Lifetime risk is 5%
• 5-10 % of ovarian cancer are linked to identifiable, inherited mutations in
certain genes
• Families in which three or more first – degree relatives have ovarian cancer
or ovarian plus breast cancer are likely to have a cancer – susceptibility
genetic mutation that is transmitted in an autosomal dominant pattern
Risk factors
• Family History
• Three familial ovarian cancer syndromes
• 1. The site specific ovarian cancer syndrome (BRCA1)
• Only ovarian cancer is seen
• Account for 10-15% of hereditary ovarian cancer
• 2. hereditary breast/ovarian cancer syndrome (BRCA2)
• Associated with 65-75% of hereditary ovarian cancer
• 3. hereditary nonpolyposis colorectal cancer syndrome (HNPCC)
• may have colon, endometrial, breast, ovarian or other cancers
• Lifetime risk is 10%
Risk factors
• Ethnicity
• Higher in white women
• Higher in North America and Northern Europe than
Japan
• BRCA1 and BRCA2 genes are more common among
White women of Ashkenzi descent
• Incidence is higher in industrialized countries
Risk factors
• Reproduction factors
• Nulliparous
• First childbirth after age 35 years
• Involuntary infertility
• Late menopause and early menarche
• Patients with prolonged period or uninterrupted ovulation
Risk factors

•Others:
• Dietary Factors: diets high in saturated animal fats seem
to confer an increased risk
PROTECTIVE FACTORS
• Oral contraceptive use – 5 year use cuts risk by half
• Multiparity: First preganancy before age 30
• Lactation
• Tubal Ligation
• Hysterectomy
Pathology
• Ovarian cancer can be divided into 3 major categories based on cell
type of origin
• The ovary may also be the site of metastatic disease by primary
cancer from another organ site
• Unlike carcinomas of the cervix and endometrium, precursor lesions
of ovarian carcinoma have not been defined
Pathogenesis
• 2 broad phases
• 1. malignant transformation
• Benign  borderline malignant
• 2. peritoneal dissemination
• Histogenetic classification categorizes ovarian
neoplasm with regards to their derivation
• COELOMIC EPITHELIUM
• GERM CELLS
• MESENCHYME (Stroma)
 Histogenetic Classification of Ovarian Neoplasms
• Derived from Coelomic Epithelium (Epithelial
Tumors)
• Serous Tumor
• Mucinous tumor
• Endometriod Tumor
• Mesonephroid (Clear Cell Tumor)
• Brenner Tumor
• Undifferentiated Tumor
• Carcinosarcoma and Mixed Mesodermal tumor
 Histogenetic Classification of Ovarian Neoplasms

• Derived from Germ Cells • Dysgerminoma

• Teratoma • Embryonal Carcinoma
• Mature Teratoma • Endodermal Sinus Tumor
• Solid Adult Teratoma • Choriocarcinoma
• Dermoid Cyst • Gonadoblastoma
• Malignant neoplasms
secondarily arising form
mature cystic teratoma
• Immature Teratoma
 Histogenetic Classification of Ovarian Neoplasms

• Derived from Specialized Gonadal Stroma

• Granulosa – Theca cell tumors
• Granulosa tumor
• Thecoma
• Sertoli – Leydig Tumors
• Arrhenoblastoma
• Sertoli Tumor
• Gynandroblastoma
• Lipid Cell Tumors
Histogenetic Classification of Ovarian Neoplasms
• Derived from Nonspecific Mesenchyme
• Fibroma, hemangioma, lipoma
• Lymphoma
• Sarcoma

• Metastatic to the ovary

• GI (Krukenberg)
• Breast
• Endometrium
• Lymphoma
Frequency of Ovarian Neoplasms (WHO)
CLASSIFIACTION FREQUENCY

Epithelial 65%

Germ Cell 20-25%

Sex Cord – stromal 6%

Lipid cell <0.1%

Gonad0blastoma <0.1%
 Bilaterality of Ovarian Tumors
Type of Tumor %
Epithelial Tumors
Serous Cystadenoma 10
Serous Cystadenocarcinoma 33-66
Mucinous Cystadenoma 5
Mucinous Cystadenocarcinoma 10-20
Endometriod Carcinoma 13-30
Benign Brenner Tumor 6
Germ Cell Tumors
Benign Cystic Teratoma 12
Immature Teratoma 2-5
Dysgerminoma 5-10
Sex Cord – Stromal Tumors
Thecoma Rare
Sertoli – Leydig Cell Tumor Rare
Granulosa – Theca Cell Tumor Rare
Diagnosis
• Ultrasound remains to be the most helpful
examination with highest sensitivity
• To supplement findings on ultrasound, tumor
markers may be used
 Tumor Tumor marker

Epithelial ovarian cancer CA 125

Mucinous adenocarcinoma CEA

Endodermal sinus tumor AFP

Embryonal cell Ca hCG, AFP

Choriocarcinoma hCG

Dysgerminoma LDH-1,2

Granulsoa Cell tumor Inhibin

EPITHELIAL OVARIAN NEOPLASMS
• 85% of malignant ovarian tumors

CELL TYPE % ALL OVARIAN NEOPLASMS % OVARIAN CANCERS

SEROUS 20-50 35-40

MUCINOUS 15-25 6-10

ENDOMETRIOID 5 15-25

CLEAR CELL <5 5

BRENNER 2-3 Rare

 EPITHELIAL OVARIAN NEOPLASMS
•CATEGORY
• BENIGN  ADENOMA
• MALIGNANT  ADENOCARCINOMA
• Borderline malignant tumor
 EPITHELIAL OVARIAN NEOPLASMS
• Papillary
• Presence of papillae
• Ex. Papillary serous cystadenoma
• Cyst
• Presence of cystic structures
• Ex. cystadenoma
• Fibroma
• When ovarian stroma predominates
• Ex. adenofibroma
Serous Cystadenoma
• Low-grade serous tumor
• Consist of ciliated epithelial cells that resemble the fallopian
tube
• Occur during reproductive years
• Borderline tumors
• Occur on women ages 30-50
Serous Carcinoma
• Most common malignant epithelial tumor
• 50% of all epithelial tumors
• 40% of ovarian cancers
• Usually cystic with solid components
• Elevated CA 125 in 80% of women with advanced disease
• Characteristic: psammoma bodies
• Neoplastic epithelium resembles that of fallopian tubes
Mucinous Cystadenoma
• Epithelial cells filled with mucin
• Multiloculated, multiseptated
• Cells resemble that of the endocervix and mimic
intestinal cells
• Found primarily during reproductive years
Mucinous Carcinoma
• 10-15% of malignant epithelial carcinoma
• Usually cystic and multilocular with some solid components
• Often larger than serous ca
• May grow as large as 50 cms
• Fluids vary form watery to gelatinous
• Neoplastic epithelium resembles large bowel or endocervix
• There is elevation of CEA in 65% of cases
Endometroid Carcinoma
• 10 -15 %
• Neoplastic cells resemble typical endometrial ca
• Squamous components are common (50% )
• Commonly arise in foci of ovarian endometriosis
• Usually unilateral and locally invasive with late
peritoneal spread
Clear cell carcinoma
• Rare
• 6% of epithelial tumor
• Neoplastic epithelium resembles mesonephric apparatus
• Strong association with ovarian endometriosis
• Frequently coexist with endometroid tumor
• Bilateral in 40 % of cases
• Locally invasive and late peritoneal spread
Hobnail appearance of
nucleus
GERM CELL TUMORS
• Represents about 20% of all ovarian tumors
• Of these, 97% are benign and 3% malignant
• Classified according too degree of differentiation
• Undifferentiated
• Dysgerminoma
• Gonadoblastoma
• Differentiated
• All other germ cell tumors
Dysgerminoma
• Most common germ cell malignancy
• 1-2% of primary ovarian neoplasm and 3-5% of ovarian
malignancies
• Can occur at any age (7 months – 70 y/o)
• Most cases occur in adolescence and early adulthood
• Most common malignant neoplasm observed in pregnancy
• Contains isolated gonadotropin – producing syncitiotrophoblast
giant cells
• Elevated serum LDH or hCG
• Grossly, tumor appears firm, fleshy, cream colored or pale tan
• Characterized histologically by the presence of large, round, ovoid or
polygonal cells with stroma infiltrated by lymphocytes
• Frequently associated with gonadoblastoma
• Predilection for lymphatic spread
• Notable for acute sensitivity to irradiation and chemotherapy
• Only germ cell tumor in which the opposite ovary is frequently
involved in the tumor process (10-20%)
• Pure dysgerminoma has good prognosis since they present early
Endodermal Sinus Tumor/Yolk Sac Tumor
• 2nd most common malignant germ cell tumor (22%)
• Median age is 19 y/o
• Almost always unilateral
• Usually large tumors (10-30cms)
• On cut surface of tumors, appear gray – yellow with areas of
hemorrhages and necrosis with cystic, gelatinous changes
• Characeristic Schiller – Duval Body
• Highly malignant
• secrete AFP
Teratoma
• Arises from single germ cell and consists of all 3 germ cell layers
(endoderm, mesoderm and ectoderm)
• Mature (benign) and immature (malignant) form
• Cystic or solid
Teratoma
• Mature Cystic Teratoma
• >90% of all ovarian teratomas
• 15% of all ovarian neoplasms
• Common in 2nd and 3rd decades on life
• most commonly seen elements are ectodermal in origin – hair, sebaceous or
sweat glands and teeth or cartilage
• Slow growing
• Benign
• Malignant degeneration – squamous cell carcinoma, rare
• Immature Teratoma
• Also consist of tissues derived from 3 germ layers
• Contain immature or embryonal elements
• 1% of ovarian teratomas
• Occurs most commonly in the 1st 2 decades of life, not common
in menopause
• Contains immature neural elements
• Almost unilateral
Embryonal Carcinoma
• One of the most malignant carcinoma of the ovary
• 4% of the malignant germ cell tumors
• Occurs at mean age of 15y/o
• Half of the patients have hormonal abnormalities, precocious puberty,
irregular uterine bleeding, amenorrhea or hirsutism
• Tumors consists of primitive cells with occasional papillary or gland – like
formations
• Ill – defined mass with areas of haemorrhage and necrosis
• The cells have eosinophilic cytoplasm with distinct borders and round
nuclei with prominent nucleoli
• Secrete hCG and AFP
Polyembryonal tumor
• Rare
• Highly malignant
• Consists of numerous embryoid bodies resembling
morphologically normal embryo
• Not sensitive to radiotherapy and response to
chemotherapy is unknown
Choriocarcinoma
• Non-gestational type is extremely rare
• Distinguished form gestational choriocarcinoma by the absence of
paternal DNA
• Admixed with other germ cell elements
• Usually occurs in prepubertal period
• Poor response to chemotherapy
• Associated with precocious puberty – mammary dev’t, growth of
axillary and pubic hair , uterine bleeding
• Secretes hCG
Gonadolastoma
• Occurs almost exclusively in patients with dysgenetic
ovaries
• 25% occurs in phenotypic males
• They have the propensity to produce malignant germ
cell tumors (Dysgeminoma)they should be removed as
soon as possible after diagnosis
Mixed Germ Cell Tumors
• 10-15% of all germ cell cancers
• Contain at least 2 malignant elements
• Majority consist of dysgerminoma or immature
teratoma with endodermal sinus tumor
• Prognosis depends on age and the most malignant
element found
TUMORS DERIVED FROM SPECIAL
GONADAL STROMA
Granulosa - Stromal Cell Tumor
• Granulosa cell tumor
• Theca cell tumors
• Fibromas
Granulosa Cell Tumor
• Occurs in any age group but with peak incidence in perimenopausal
women
• Produce estrogen and few are androgenic
• Appear grossly as solid tumor that are soft or firm depending on the
neoplastic cells
• Sometimes resembles mucinous cystadenocarcinoma but on cut
section, contains serous fluid with blood clots
• 2 subtypes
• Adult – account for 95% of all granulosa cell tumors
• Occur more commonly in postmenopausal women
• m/c tumor that produces estrogen
• Associated with endometrial hyperplasia and carcinoma
• Causes postmenopausal bleeding
• Histologically, fibrothecomatous components are common with scanty
cytoplasm
• Call – Exner bodies – coffee – bean grooved cells which may be arranged
in clusters surrounding a central cavity which resembles primordial cells
• Juvenile type
• Most occur during 1st 3 decades of life
• Hormonally active and produces estradiol, progesterone and androgens
• Causes Sexual precocity
• Histologically, fibrothecomatous components are common with abundant cytoplasm, with numerous
mitosis, with dark nuclei and rarely demonstrate Call – Exner bodies
• High cure rate
Sertoli – Leydig Cell Tumor
• Acct for <1% of all primary ovarian tumors
• Mixture of sertoli and leydig cells
• Average age of dx is 25 y/0
• Majority are androgenic
• Patient classically presents with hirsutism and virilization
• Histologically: tubules lined with sertoli cells and sheet of leydig
cells
FIGO Staging
Management