Prof. Abdulhafid Abudher MBBch,DGO,MD,FABOG,FRCOG Introduction Fifth most common cancer in women Fifth most frequent cause of cancer death 1 in 70 newborn girls will develop cancer during her lifetime Disease of postmenopausal women and all ages Year 2000 23000 new cases 14000 deaths Etiology Cause is unknown Predisposing factors Repeated ovulation Infertility treatment PCO 2.5 fold increase Unopposed estrogen therapy Etiology Increase risk by High diet in saturated animal fats Alcohol and milk (never confirmed) Exposure to talk powder Etiology Protective factors Chronic anovulation Multiparty Breast feeding Pregnancy -reduction 13-19% per pregnancy COC Pills decrease by 50% for 5 years and more of use Over 90% develop sporadically 10% of epithelial based on genetic predisposition Turner syndrome(45,XO) dysgerminoma and gonadoplastoma Two first degree relatives –risk 50% hereditary In two forms Breast and ovarian syndrome (BOC) Germline mutation in BRCA1 gene on chromosome 17(2844%) Less common BRCA2 on chromosome 13 (1/800) Lyncy II syndrome (hereditary nonpolyposis colorectal cancer syndrome )HNPCC Histopathology Divided to three categories according to cell type of origin Epithelia neoplasms Germ cell neoplasms Sex cord and stromal neoplasms May be the site of metastatic disease Neoplasms metastatic to the ovary 1-Epithelia neoplasms Tend to occur in the sixth decade of life Derived from the ovarian surface mesothelial cells , six types: Serous Mucinous endometroid clear cell Transitional cell undifferentiated Account for over 60% of all ovarian neoplasms More than 90% of malignant ovarian tumors Ovarian serous cystadenocarcinoma Most common 35-50% of all epithelial tumors Bilateral in 40-60% 85% with extra ovarian spread at diagnosis Over 50% exceeds 15 cm, solid areas, hemorrhage, cyst wall invasion Most poorly dfferentiated Mucinous neoplasms 10-20% of epithelial ovarian tumor Second most common type of epithelial ovarian carcinoma Bilateral in less than 10% Average size is 16-17 cm (large) ,multilocular ,viscous mucus Pseudomyxoma peritonei Unusual condition Associated with mucinous neoplasms of ovary Progressive accumulation of mucinous in abdominal cavity May be associated with appendix Benign Potentially morbid ,intestinal obstruction Mortality rate approaches 50% Endometroidal neoplasm Adenometroidal pattern Bilateral in 30-50% 30% of patients will have endometrial carcinoma of uterus as primary Clear cell carcinoma Called mesonephroid carcinoma 5% of epithelial ovarian cancer Small size Aggressive ,hypercalcimeia ,hyperpyrexia Cystic and solid Transitional cell carcinoma Brenner Newly described Present with advanced stage Poorer prognosis Undifferentiated carcinoma Accounts for less than 10% of epithelial Absence of any distinguishing microscopic features that permit its placement in one of the other histologic categories. 2-Germ cell neoplasms Tend to occur in second and third decade of life Better prognosis Many produce biological markers Types: Dysgerminoma Young females (Seminoma in male) 30-40% of germ cell tumors Unilateral in 85-90% Solid Endometrial sinus tumor Was called yolk sac tumor Second most common germ cell tumor Occurs in 20% of cases Bilateral in less than 5% Commonly present with acute abdomen Produces AFP Immature teratomas Malignant counterpart of mature cystic teratoma 20% of germ cell neoplasms Bilateral in less than 5% Elevated serum AFP Three germ layers Immature neuroectodermal element Mature teratomas Common at age 20 to 30 Most common neoplasm diagnosed during pregnancy Less than 2% goes malignant after age of 40 Embryonal carcinoma Very rare in pure form HCG and AFP are usually elevated Choriocarcinoma rare germ cell tumor unrelated to pregnancy Lower elevation HCG May cause precocious puberty, uterine bleeding or amenorrhea Gonadoblastoma Rare More common on the right than left ovary Occur in second decade of life Associated with presence of Y chromosome Mixed germ cell tumors Accounts for 10% of germ cell tumor Contains two or more germ cell elements dysgerminoma and endometrial sinus tumor ocurs together 3-Sex Cord-Stromal tumors Granulosa cell tumor 1-2% of all ovarian neoplasms Most common malignant tumor of sex cord-sromal Associated with hyperestrogenism May cause precocious puberty(girls) ,adenomatous hyperplasia and vaginal bleeding(postmenopausal women) Ovarian thecoma Associated with hyperesrogenism Benign tumor Ovarian fibroma Benign tumor Associated with Meig’s syndrome Sertoli-stromal cell tumors Rare consist of testicular structures Occur during third decade Usually virilizing Rarely bilateral 4-Neoplasms metastatic to the ovary Accounts for 25% of all ovarian malignancy Mimic primary ovarian cancer Present as bilateral adnexal masses 25% unilateral Common primary cancers Breast (40%_ Stomach (Krukenberg tumors) Colon endometrium Diagnosis of ovarian Cancer Insidious disease Non specific GIT complains Abdominal distention Pelvic weight Menstrual abnormalities in 15% Rarely excessive estrogens or androgens Screening Routine pelvic examination Ultrasound examination Tumor markers CA-125 antigen from fetal amniotic and coelomic epithelium TAG 72 ,M-CSF ,OVX1 Evaluation of the patient with suspected ovarian neoplasm Child and postmenopausal women at great risk of malignancy Reproductive women is likely to have functional cyst or endometrioma Differential diagnosis is influenced by Age Characteristic of the mass on pelvic examination Radiographic appearance Physical Examination Comprehensive examination Lymph node , Sister Mary Joseph’s nodule Abdomen examination Pelvic examination Characteristics Benign Malignant Mobility Mobile Fixed Consistency Cystic Solid or Firm Bilateral/Unilate Unilateral ral Bilateral Cul-de-sac Nodular Smooth Radiographic Evaluation Trans abdominal ultrasound Trans vaginal ultrasound Color flow Doppler Consistency Simple cyst <10cm in size Solid or cystic and solid Septations Septations <1mm in thickness Multiple septations >3mm in size Uni or bilateral unilateral Bilateral others Calcification, teeth ascites Radiographic Evaluation,,,, Computed tomography (CT) Pelvic organs and Retroperitoneal structures Magnetic resonance imaging (MRI) Nature of ovarian neoplasm X ray chest Barium enema mammogram Laboratory Evaluation CBC Serum electrolytes hCG (pregnancy) AFP ,LDH lactate dehydrogenase (young girls) CA-125 Surgical Treatment of Epithelial Cancer Surgery is the corner stone of therapy Surgical staging to Reduce amount of disease Evaluate the extent of spread Debulking or cytoreduvtive surgery is removal Primary tumor Associated metastasis disease Intra operative differentiation Benign Malignant Simple Unilateral No adhesions Smooth surface Intact capsule Adhesions Rupture Ascites Solid areas Areas of hemorrhage or necrosis Multi loculated mass Bilateral Most common location of metastases Peritoneum 85% Omentum 70% Liver 35% Pleura 33% Lung 25% Bone 15% Procedures in staging Sample of ascites or peritoneal washings from Para colic gutters , pelvic and sub diaphragmatic for cytology Complete abdominal exploration Intact removal of tumor Infracolic omentectomy Biopsies of abdominal peritoneal implants Pelvic and Para aortic lymph node biopsies Cytoreduvtive surgery to remove all visible disease International Federation of Gynecology&Obstetrics (FIGO) Staging Stage I. growth limited to the pelvis Ia- One ovary Ib- both ovaries Ic- Ia or Ib and ovarian surface tumor ,rupture capsule, malignant ascites, peritoneal cytology positive. Stage II. Extension to the pelvis IIa- extension to the uterus or fallopian tube IIb- extension to the other pelvic tissues IIc- IIa or IIb and ovarian surface tumor ,rupture capsule, malignant ascites, peritoneal cytology positive. Stage III.Extension to abdominal cavity IIIa- abdominal peritoneal surfaces with microscopic metastases IIIb- tumor metastases <2cm in size IIIc- tumor metastases >2cm or metastatic disease in pelvic para aortic or inguinal lymph nodes Stage IV. Distant metastases Malignant pleural effusion Pulmonary parenchymal metastases Liver or splenic paranchyml metastases Metastases to thr supraclavicular lymph nodes or skin Surgical treatment of Germ Cell Neoplasms Most are at early stage on young women Removal of involved adnexia Same complete surgical staging Chemotherapy of epithelial cancer Stage Ia and grade I, don’t need treatment Agents ,cisplatin, carboplatin, cyclophosphamide, paclitaxel Compination paclitaxel 175mg/m2 and cisplatin 75mg/m2 or carboplatin for 6 cycles at 3 week intervals Toxic effects Vomiting ,diarrhea ,alopecia, nephro and ototoxicity and myelosuppression. Chemotherapy of Germ Cell Neoplasms Curable Dysgerminoma most radiation sensitive Preserve future reproductive potential with chemotherapy Regimens ,vinblastine-bleomycin-cisplatin , vincristinactinomycin, D-cyclophsphomide, bleomycinetoposide-cispltin Complications of chemotherapy Nausea vomiting alopecia Agent Toxicity Cisplatin Carboplatin Cyclophosphamid e Paclitaxil Altretamin Etoposide Bleomycin Doxorubicin Vincristine ifosfamide Nephrotoxicity,neurotoxicity, ototoxicity Thrombocytopenia, neutropenia Hemorrhagic cystitis, pulmonary fibrosis Myelosuppression Peripheral neuropathy Myelosuppressiom Pulmonary fibrosis Cardiac toxicity Neurotoxicity Hemorrhgic cystitis,central neurotoxicity Radiation therapy and alternative Very limited role in epithelial cancer Dysgerminoma Immunotherapy Gen therapy prognosis Related to Response to chemotherapy Differentiation of tumor Germ cell better than epithelial Stage of the disease -5 year survival rate (epithelial) Stge I -75-93% stageII- 65-74% Stage III- 23-41% Stage IV- 11%