Malignant Ovarian Tumors

Overview and Epidemiology

-80% ovarian tumors benign -Ovarian cancer accounts for 25% of all gyn malignancy but is responsible for over 50% of gyn malignancy deaths (lack of effective screening tools for early diagnosis, spread by direct extension into the peritoneal cavity) -5-year survival is 25-45%: High degree of suspicion, prompt diagnosis and intervention

Pathogenesis
-3 distinct components of the ovary: surface epithelium, ovarian germ cells, and ovarian stroma -90% of ovarian cancers originate from the epithelium, on the ovarian capsule -5% are metastatic (Krukenberg tumors) -Malignant transformation of ovarian tissue after prolonged periods of chronic uninterrupted ovulation (ovulation disrupts ovarian epithelium, cell repair mechanisms, opportunity for gene deletions and mutations)- e.g. early menarche, infertility, nulliparity, delayed childbearing, late-onset menopause, and increasing age Risk factors Familial syndromes, family hx br/ov canc. Personal hx br canc. Early menarche Infertility Nulliparity Increasing age Late menopause Obesity Protective factors Oral contraceptives (suppress ovulation) Multiparous Breastfeeding Tubal ligation **, hysterectomy Hysterectomy Chronic anovulation

-Primarily spreads by direct exfoliation of malignant cells, and so mets wherever peritoneal fluid goes (umbilicus: Sister Mary Joseph nodule); also can spread lymphatically to para-aortic lymph nodes; lung and brain get mets from hematogenous spread -Carcinomatous ileus: intermittent bowel obstruction from advanced intraperitoneal spread that causes ascites and encasement of the bowel with tumor -10-15% of ovarian cancer is due to a familial syndrome (Lynch II syndrome/HNPCC, BRCA1, some BRCA2)

Clinical
-asx, or vague complaints (bloating, urinary frequency, weight loss) until advanced stages; later, ascites and SOB from pleural effusion -may feel solid, irregular pelvic mass on physical exam

Diagnosis
-Pelvic ultrasound is the primary diagnostic tool (can distinguish benign, malignant) Benign Malignant Size <8 cm >8 cm Uni/bilateral Unilateral Often bilateral Consistency Cystic Solid (or cystic and solid) Solid components Not present Nodular, papillary Septations Not present, or singular Multilocular, thick (>2 mm) Doppler flow Not present Present in the solid parts Other Calcification, teeth Ascites, peritoneal masses, lymphadenopathy CA-125: not routinely used to screen, but instead, used to follow Pre-menopause: CA-125 can be elev in leiomyomata, PID, endometriosis, pregnancy Post-menopause: CA-125 can be helpful in predicting higher likelihood of malignant tumor rather than benign. CA-125 is often normal, even in advanced cancer, and therefore cannot rule out ovarian cancer.

Staging
-Surgical staging, surgical treatment -75% of patients present with stage III or IV (epithelial tumors are slow growing so remember, patients can be asymptomatic) -I: growth limited to the ovaries -II: extension to pelvis (uterus, fallopian tube, etc) -III: extension to the abdominal cavity (peritoneal surface, lymph nodes) -IV: distant mets (pleural effusion, pulmonary parenchyma, liver or spleen parenchyma, or supraclavicular lymph nodes)

Types
Borderline ovarian tumors:10% of seemingly benign epithelial cell tumors may contain histology showing intraepithelial neoplasia. Generally remain confined to the ovary, but are more common in premenopausal women. Malignant tumors often have benign counterparts, and if benign counterpart is found in a patient, bilateral removal is considered, because there is a possibility of future malignant transformation of remaining ovary. Epithelial Cell Ovarian Carcinomas- Most Common Ovarian Cancers CA-125 is elevated in 80%, use to track treatment, recurrence, not screening 1. Malignant epithelial serous tumors (serous cystadenocarcinoma) is most common, and 50% of these derive from serous cystadenoma (benign precursor). Can have psammoma bodies.

2. Malignant mucinous epithelial tumors (mucinous cystadenocarcinoma) are not as common as benign ones, and may be associated with pseudomyxoma peritonei 3. Endometrioid are mostly malignant, often coincident with endometrial cancer (uterine) 4. Clear cell carcinoma- mesonephric? 5. Brenner- transitional epithelium, may be found with mucinous cystadenoma Germ Cell Carcinomas- Most Common Ovarian Cancer in <20 yo age group -Benign (95%), malignant (5%) -Malignant: most commonly 1. dysgerminomas (assoc w/ Turners), 2. immature teratomas and 3. yolk sac tumors -Contrast w/above: grow rapidly, unilateral, stage I at diagnosis -Rapid growth distends ovarian capsule and causes hemorrhage, necrosis and acute pelvic pain Germ cell tumor Dysgerminoma Immature teratoma Endodermal sinus/ Yolk sac Choriocarcinoma Marker LDH N/A AFP hCH

Sex Cord-Stromal Tumors -functioning tumors: hormone production 1. Granulosa cell tumor (most common): often secrete large amounts of estrogen and therefore may cause endometrial hyperplasia or endometrial carcinoma. Endometrial sampling is especially important in this case. 2. Sertoli-Leydig cell tumors (arrhenoblastoma) are rare, testosterone-secreting. Often postmenopausal patients with hirsutism or virilization.

Management
-Cytoreductive surgery, or tumor debulking -adjunctive radiation and chemotherapy are more effective when tumor mass < 1 cm -TAHBSO (total abdominal hysterectomy, bilateral salpingo-oophorectomy), plus partial omentectomy, peritoneal washings, Pap smear of diaphragm, sampling of pelvic and paraaortic lymph nodes -Adjunctive treatment with paclitaxel combined with carboplatin -Post-chemo: CA-125 and CT imaging to evaluate success (NOT second-look lap) -Recurrent disease (frequent): combination chemotherapy