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Neoplasms of the Ovary and Normal Histology Pincas Bitterman, MD 2019

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Neoplasms of the Ovary and Normal Histology Pincas Bitterman, MD 2019 Neoplasms of the Ovary and Normal Histology Pincas Bitterman, MD 2019 Epithelial ovarian tumors Sub-types Brenner tumor BRCA1/BRCA2 Borderline tumors Tumors with "coffee-bean" nuclei Pseudomyxoma peritonei Germ cell tumors Benign and malignant Mature cystic teratoma (Dermoid cyst) Dysgerminoma Schiller-Duval bodies Sex Cord-Stromal Tumors Fibroma Granulosa cell tumor Call-Exner bodies Metastatic tumors to the ovary Most common sites Krukenberg tumor OVARIES ● Most common lesions are functional cyst which are benign, and non-malignant neoplasms. ● Functional cysts include Follicular cysts and Luteal Cysts. Patients may present with or without symptoms, or vaginal bleeding with or without a pelvic mass. ● The incidence of ovarian cancer increases with age. Early detection is problematic as generally the patients have no symptoms and present at high stage (II-III) where the tumor has spread to other sites inside or outside the pelvis. ● Ovarian cancer is the #1 killer among female genital malignancies in the US ● Inflammation ○ Oophoritis . Associated with PID . Autoimmune, rare ● Non-Neoplastic and Functional Cysts ○ Follicular and luteal cysts . Very common: physiologic? . Unruptured graafian follicles . Ruptured follicles which sealed immediately . Usually multiple, about 2cm in diameter . Lined by granulosa and thecal cells Theca cells may be luteinized ○ Corpora lutea . Lined by luteinized granulosa cells ○ Polycystic Ovaries (former name: Stein Leventhal syndrome). May be associated with stromal hyperthecosis . Stromal hyperplasia is not unusual ▪ Affects 3% - 6% of reproductive-age women ▪ Very conspicuous luteinized thecal cells . estrogen production . Endometrial hyperplasia on occasion . Most common in postmenopausal women . Numerous follicle cysts Subcortical . Enlarged ovaries Twice the normal size . Thickened cortex . Absence of corpora lutea . Clinical presentation Oligomenorrhea Anovulation Obesity Hirsutism Virilism (rarely) . Microscopic appearance Concordant with the gross view: Cysts etc . Clinical course Persistent anovulation Obesity Hirsutism, virilization ● Neoplastic Processes ○ Review of histology is absolutely necessary for understanding and diagnosis ○ Malignant tumors represent 6% of all cancers in females in the USA ▪ Incidence ranks below uterine and cervical cancers ▪ Not commonly detected at early stage ▪ Risk factors include Nulliparity or low parity Gonadal dysgenesis in children Family history Heritable mutations (BRCA – 5% of patients < 70 years old- and BRCA2) • These increase the susceptibility to ovarian cancer, but not borderline tumors • 20% to 60% by the age of 70 • Most cancers are Serous Better than 90% of serous carcinomas show mutations in the tumor-suppressor gene p53 Oral contraceptives and tubal ligations appear to be protective ○ The majority of ovarian tumors are benign . Once removed, the patient is “cured” ○ The incidence of malignancy increases with age ○ The size of the tumor is generally unrelated to its behavior, (benign versus malignant ○ Behavior of malignant tumors depends primarily on the grade and stage of the tumor . Borderline (Atypical proliferative) Tumors No destructive stroma invasion Implants which are not clear cut malignant Chemotherapy only with metastatic carcinoma About 5% die from disease metastatic carcinoma is not present . Malignant Destructive stromal invasion Metastasis ▪ Risk factors for malignant tumors include: . Nulliparity . Family history . Gonadal dysgenesis in children . Genetic BRCA1 and BRCA2 mutations Lynch syndrome II ○ The classification of ovarian tumors is based on the most probable tissue/cell of origin . Surface coelomic epithelium Serous (Serous intraepithelial carcinoma, (STIC). Mucinous, etc. Germ cells These migrate to the ovary from the yolk sac at the 5th to sixth week of gestation . Ovarian stroma . Metastatic ○ The majority of tumors are nonfunctional ○ Most become symptomatic because of their size ○ Many have spread prior to surgery ○ Some epithelial tumors tend to be bilateral – review table ○ Metastatic tumors have a tendency to be bilateral ○ Stroma tumors are generally unilateral ○ Malignant germs cell tumors are most often unilateral ○ Occasional symptoms include: . Abdominal/pelvic pain . Abdominal distention – ascites . Urinary and gastrointestinal symptoms . Vaginal bleeding ○ Prognosis is determined by type of tumor, STAGE and GRADE ○ Epithelial tumors . Most common . Size: small or massive ○ Histologic types . Serous (lined by tall columnar ciliated cells-tubal-like) Filled with clear fluid All types of serous tumors (benign, borderline, and malignant) account for 30% of all ovarian tumors. 75% are benign or borderline. Of the 25% malignant, 40%-50% are serous Benign tumors are generally cystic, with a smooth and glistening cut surface. Borderline tumors show a range of papillary projections. Malignant tumors show multifocal solid areas which may be associated with cysts. Bilaterality: 20% in cystadenomas; 30% of borderlines and approximately 65% in carcinomas Generally originate from the surface epithelium Cystadenomas Cystadenofibroma Benign ▫ Variant with more proliferation of the fibrous stroma associated with the epithelium ▫ Benign, small, multilocular with small, simple fibrotic, papillary processes. ▫ Depending on the lining epithelium, they may be serous, mucinous, endometrioid, transitional (Brenner), or rarely clear ▫ Borderline or malignant types are extremely rare Adenofibromas Carcinoma (STIC). ○ Morphology . Serous . Benign: cuboidal/columnar epithelium with cilia without nuclear stratification . Borderline: Complexity of papillae, nuclear stratification, nuclear atypia, few mitotic figures, but NO DESTRUCTIVE STROMAL INVASION; Microinvasion . Calcifications (psammoma bodies on occasion). Malignant: Destructive stromal invasion associated with marked nuclear atypia, numerous mitotic figures, large, edematous papillary structures . Borderline and malignant tumors may involve the ovarian surface Micropapillary tumors: areas of borderline and carcinoma, but low grade. Implants/metastasis; large intra-abdominal masses. 5-year survival rates range from 100%-70% if confined to the ovary, and 25% to 95% with peritoneal involvement, in carcinomas and borderline tumors respectively. Borderline tumors may recur after several years Mucinous Lines by mucinous epithelium similar to the cervix or colon without cilia. They represent 20%-25% of all ovarian tumors Mostly occur in middle adult life > 90% are benign or borderline Mucinous carcinomas account for < 5% of ovarian cancers Grossly: numerous cysts and rare surface involvement The majority show abundant gland-like or papillary structures with nuclear atypia and stratification if borderline or malignant. Carcinomas contain solid areas, marked nuclear atypia, numerous mitotic figures and necrosis plus INVSION OF THE STROMA • Intraepithelial carcinoma Some originate in endometriosis and are rarely carcinomas 10-year survival rate in borderline, noninvasive and invasive is about 95%, 90% and 55% respectively Endometrioid 20% of all ovarian cancers The great majority are carcinomas Occasionally benign: cystadenofibromas 30% associated with endometrial cancer >25% coexist with endometriosis Grossly: combination of solid and cystic areas Morphology: Lined by cells resembling endometrium 40% are bilateral 5-year survival in stage I is around 75% Clear Cell Adenocarcinoma Less common than the others May occur in association with endometriosis or endometrioid carcinoma May be solid or cystic Characterize by epithelial cells with abundant clear cytoplasm arranged in sheets, tubules, or cysts 5-year survival rate of approximately 60% when confined to the ovary. If not, survival is generally < 20% Transitional cell tumors Benign transitional cell tumor (Brenner). Rare adenofibromas Solid or cystic tumors Unilateral (90%) From microscopic lesions up to 30 cm. Small lesions (1cm -2cm) are more common Transitional epithelium resembling the epithelium of the urinary tract with ‘coffee bean’ nuclei Tumor nests in a fibrous stroma The nests may show glandular spaces lined my mucinous epithelium Rarely contain a plum cellular stroma with hormonal activity Greater than 95% are benign with rare borderline and malignant counterparts If malignant without a classic Brenner tumor component, they are characterized as TRANSITIONAL CELL CARCINOMA ○ Clinical Course, Detection, and Prevention of Surface Epithelial Tumors . Benign tumors are cured with resection . Characteristic symptoms when the tumors are large include: Lower abdominal pain Abdominal enlargement Gastrointestinal complains Urinary symptoms (frequency, dysuria) Pelvis pressure and pain etc. If malignant, additional symptoms may include weakness, weight loss and cachexia, particularly as the tumors progresses Ascites: Accumulation of fluid If the tumor has infiltrated the peritoneal cavity: • Malignant cells may be present in the fluid Advanced tumor show lymph node involvement and metastasis to the pelvis, abdomen, thorax, and other sites Generally diagnose when the tumor has spread with a consequent guarded prognosis Early detection is the key to achieve a better prognosis, however, blood markers have been somewhat elusive up to this point ▫ CA-125: high molecular weight glycoprotein is elevated in 80% of patients with serous and endometrioid cancer, however, its elevation is non-specific as benign tumors
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