Malignant Ovarian Neoplasms By Salah T. Fayed, MD Prof OB & GYN Gynecologic Oncology Unit Ain Shams University Cairo, Egypt

WHY? Uterus gives rise to carcinoma or sarcoma Cervix gives rise to carcinoma or sarcoma Vulva and vagina almost exclusively give rise to carcinoma only While Ovary can give rise to more than 20 types of ovarian cancers

BECAUSE Ovary is a Unique Organ with Complex Embryological Origin and Structure It has celomic surface epithelium Germ cells Specialized stroma Non-specialized stroma

Malignant Ovarian Tumors Primary: Common Epithelial Germ cell Sex cord-stromal Others Secondary: Breast GIT Uterus Lymphoma-Leukemia

According to the cell of Origin Epithelial Ovarian Cancer: papillary serous. Endometrioid, mucinous, clear cell, undifferentiated)

Germ cell tumors: Dysgerminoma, Endodermal Sinus, Immature teratoma, Non-gestational Choriocarcinoma Mixed germ cell tumors

Sex cord stromal tumors Granulosa cell tumor ( feminzing) Sertoli-Leydig cell tumor (masulinizing)

Non-specialized stroma Lymphoma Sarcoma

Different types of ovarian tumors have: Different biological behavior Different incidence Different age of occurrence Different risk factors Different strategies of management

Epithelial Ovarian Cancer (EOC) Epidemiology Comprise 85% of ovarian cancer Its rank differs in developed and under-developed countries It is the first in Scandinavian countries and the second in united states after endometrial It is less common among black races and in Latin America

Epithelial Ovarian Cancer: Epidemiology A disease of post-menopausal women, although young patients in their twenties and thirties are not immune Peak incidence at 60 years No parity and low parity increase the risk High parity and hormonal contraception decrease the risk Constitute 23% of gyn. Cancers and responsible for 47% of gyn. Cancer Deaths

Epithelial Ovarian Cancer: Pathogenesis As most of the cancers no definite etiology Genetic factors are important Women with a first degree relative with EOC have higher relative risk History of breast cancer increases the relative risk Excessive induction of ovulation may increase the risk Repeated trauma of ovulation may play a role in theory

EOC: Histological Types The most common varieties are: Papillary serous cystadenocarcinoma Endometrioid adenocarcinoma Mucinous cystadenocarcinoma Clear cell carcinoma Undifferentiated carcinoma

EOC: Spread Trans-peritoneal, the commonest as it is the only intra-peritoneal organ Direct infiltration of near-by organs Lymphatic to retro-peritoneal pelvic and para-aortic LN, rarely to inguinal and supraclavicular LN Blood to distant organs and to liver parenchyma

Ovarian Cancer: Staging Stage I: Confined to the Ovary (a, b &c) Stage II: Confined to the pelvis (a, b &c) Stage III: Abdomen and liver surface (a, b &c) Stage IV: Liver Parenchyma, positive pleural effusion or distant metastases These are the essential unforgettable elements of ovarian cancer stages

Early Ovarian Cancer I & II Stage I Ia: one ovary Ib: both ovaries Ic: Either + positive peritoneal cytology Stage II IIa: Genital IIb: extra-genital IIc: Either + positive peritoneal cytology

Late Ovarian cancer: III & IV Stage III (Abdominal) IIIa: Microscopic IIIb: < 2 cm nodules IIIc: > 2 cm nodules or (pelvic or para-aortic) LN metastases Stage IV Distant metastases Positive pleural effusion Parenchymatous liver metastases

EOC: Diagnosis Early: Adnexal Mass, usually accidentally discovered as during the infertility workup Late: The common presentation is vague abdominal discomfort, progressive abdominal enlargement, anorexia, weight loss, edema of the lower limbs, obstructive intestinal symptoms Unfortunately 75% of EOC patients present late as stage III & IV with poor prognosis

Clinical Findings: General & Abdominal Pallor is a common finding Jaundice is a late sign of liver metastases Lymphadenopathy including inguinal LN Lower limb edema (hypoproteinemia and venous compression) Ascites that may be tense Pelviabdominal mass Epigastric mass (Omental cake)

Clinical Findings: Pelvic Adnexal mass (mobile or fixed) Pelviabdominal mass Frozen pelvis with amalgamation of the whole pelvic viscera Hard nodular mass in Douglas pouch A mass may infiltrate the rectal wall (PR)

Investigations Pelviabdominal Ultrasonography Pelviabdominal CT Chest X-Ray Upper and Lower GI Endoscopy (to exclude primary GI malignancy) Serum tumor marker (CA125) Taping and cytological examination of Ascites Routine pre-operative investigations

EOC: Management Exploratory Laparotomy For Surgical Staging and Debulking: Peritoneal Wash TAH & BSO Omentectomy Palpation of the whole abdominal cavity Excision of all resectable tumor masses Pelvic and para-aortic LN sampling

Surgical Debulking Ovarian Cancer

Excision of involved organs

EOC: Management Definitive Diagnosis is established only after surgical staging and histopathological examination Almost all cases require post-operative Chemotherapy after Surgical Debulking

EOC Management cont. Combination Chemotherapy is the rule Common regimens are: Platinum-Cyclophosphamide (CP), accepted Platinum-Paclitaxel (Taxol), standard

EOC: Prognosis & Survival Tumor stage is the most important prognostic factor 5-year survival ranges from 90% for stage Ia to 10% for stage IV Optimal debulking is an independent prognostic factor (residual masses < 1 cm) Sensitivity to chemotherapy Age: Younger patients have better prognosis

EOC: Radiotherapy It has very limited role in Ovarian Cancer Its complications limits its use specially in presence of effective chemotherapy Intra-peritoneal Radioactive Phosphorus is the only type of radiotherapy used nowadays Its role is to eradicate microscopic residuals

EOC: Follow Up Follow up is mandatory Serum tumor marker CA125 is the mainstay of follow in non-mucinous tumors Clinical Examination every visit Pelviabdominal U/S and CT are useful Second look operations are NOT routienly done The benefit of secondary debulking is doubtful Second line chemotherapy in case of recurrence

EOC: cause of death Intestinal obstruction is the most common Drug toxicity from chemotherapy Coincidental thromboembolic disease Metastases in vital organs as liver and brain

Borderline Ovarian Tumors (LMP) A variety of epithelial tumors that grow slowly and have a tendency to recur after surgical removal Mucinous is the most common followed by endometrioid and serous types Multilayering, Atypia with NO stromal invasion are essential for diagnosis of Borderline Tumors

Borderline ovarian tumors (cont.) Usually present as stage I but advanced stages III are sometimes seen Treatment is essentially surgical with no role for Chemotherapy

Thank You Dr. Salah Fayed