Neoplastic Diseases of The Ovary

NEOPLASTIC DISEASES
OF THE OVARY
CHARISSE ZYLMA T. HURTADO, 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 years use cuts risk by half

 Multiparity: First pregnancy before age 30
 Lactation
 Tubal Ligation
 Hysterectomy
 Lactation
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
 Derived from Germ Cells  Dysgerminoma

 Teratoma  Embryonal Carcinoma
 Mature Teratoma  Endodermal Sinus Tumor
 Solid Adult Teratoma
 Chroiocarcinoma
 Dermoid Cyst
 Strumma Ovarii
 Gonadoblastoma
 Malignant neoplasms secondarily
arising form
mature cystic teratoma
 Immature Teratoma
 Derived from Specialized Gonadal Stroma

 Granulosa – Theca cell tumors
 Granulosa tumor
 Thecoma
 Sertoli – Leydig Tumors
 Arrhenoblastoma
 Sertoli Tumor
 Gynandroblastoma
 Lipid Cell Tumors
 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
FIGO Staging
EPITHELIAL OVARIAN CANCERS
 80-90% of malignant ovarian tumors

 TYPES:
 Serous - 42%
 Mucinous - 12%
 Endometriod - 17%
 Clear cell - 6%
 Undifferentiated – 17 %
Serous Carcinoma
 Most common malignant epithelial tumor

 50% of all epithelial tumors
 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 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
GERM CELL TUMORS
 Represents about 20% of all ovarian tumors
 Of these, 97% are benign and 3% malignant
 Classified according to 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
 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
 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
 The cells have eosinophilic cytoplasm with distinct bordersand 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
Sertoli – Leydig Cell Tumor
POSTTEST
Pathognomonic histopath findings:
1. Psammoma bodies
2. Coffee-bean shaped with abundant stroma
3. Hobnail cells
4. Call-Exner bodies
5. Schiller Duval bodies
 Tumor Markers
6. Dysgerminoma
7. Yolk sac tumor/Endodermal sinus tumor
8. Choriocarcinoma
9. Granulosa cell tumor
10. Sertoli Leydig Cell Tumor
THANK YOU.

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NEOPLASTIC DISEASES

 27% of gynecologic cancers

 Oral contraceptive use – 5 years use cuts risk by half

 Derived from Germ Cells  Dysgerminoma

 Derived from Specialized Gonadal Stroma

 Metastatic to the ovary

 80-90% of malignant ovarian tumors

 Most common malignant epithelial tumor

 10-15% of malignant epithelial carcinoma

 Most common germ cell malignancy

 2nd most common malignant germ cell tumor (22%)

 Mature Cystic Teratoma

 One of the most malignant carcinoma of the ovary

 Non-gestational type is extremely rare

 Occurs almost exclusively in patients with dysgenetic ovaries

 10-15% of all germ cell cancers

Pathognomonic histopath findings:

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