Prof. Abdulhafid AbudherMBBch,DGO,MD,FABOG,FRCOG

IntroductionFifth most common cancer in womenFifth most frequent cause of cancer death1 in 70 newborn girls will develop cancer

during her lifetimeDisease of postmenopausal women and all

agesYear 2000

23000 new cases14000 deaths

Etiology Cause is unknownPredisposing factors

Repeated ovulationInfertility treatmentPCO 2.5 fold increaseUnopposed estrogen therapy

Etiology Increase risk by

High diet in saturated animal fatsAlcohol and milk (never confirmed)Exposure to talk powder

EtiologyProtective factors

Chronic anovulationMultipartyBreast feedingPregnancy -reduction 13-19% per pregnancyCOC Pills decrease by 50% for 5 years and

more of use

Over 90% develop sporadically10% of epithelial based on genetic

predispositionTurner syndrome(45,XO) dysgerminoma and

gonadoplastomaTwo first degree relatives –risk 50%

hereditaryIn two forms

Breast and ovarian syndrome (BOC) Germline mutation in BRCA1 gene on chromosome

17(28-44%) Less common BRCA2 on chromosome 13 (1/800)

Lyncy II syndrome (hereditary nonpolyposis colorectal cancer syndrome )HNPCC

HistopathologyDivided to three categories according to cell

type of originEpithelia neoplasmsGerm cell neoplasmsSex cord and stromal neoplasms

May be the site of metastatic disease Neoplasms metastatic to the ovary

1-Epithelia neoplasmsTend to occur in the sixth decade of life Derived from the ovarian surface mesothelial cells ,

six types:SerousMucinous endometroid clear cellTransitional cellundifferentiated

Account for over 60% of all ovarian neoplasmsMore than 90% of malignant ovarian tumors

Ovarian serous cystadenocarcinomaMost common 35-50% of all epithelial tumorsBilateral in 40-60%85% with extra ovarian spread at diagnosisOver 50% exceeds 15 cm, solid areas,

hemorrhage, cyst wall invasion Most poorly dfferentiated

Mucinous neoplasms10-20% of epithelial ovarian tumorSecond most common type of epithelial

ovarian carcinomaBilateral in less than 10%Average size is 16-17 cm (large) ,multilocular

,viscous mucus

Pseudomyxoma peritoneiUnusual conditionAssociated with mucinous neoplasms of ovaryProgressive accumulation of mucinous in

abdominal cavityMay be associated with appendixBenignPotentially morbid ,intestinal obstructionMortality rate approaches 50%

Endometroidal neoplasmAdenometroidal patternBilateral in 30-50%30% of patients will have endometrial

carcinoma of uterus as primary

Clear cell carcinomaCalled mesonephroid carcinoma5% of epithelial ovarian cancerSmall sizeAggressive ,hypercalcimeia ,hyperpyrexiaCystic and solid

Transitional cell carcinomaBrenner Newly describedPresent with advanced stagePoorer prognosis

Undifferentiated carcinomaAccounts 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 neoplasmsTend to occur in second and third decade of life Better prognosisMany produce biological markersTypes:

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 tumorsGranulosa cell tumor

1-2% of all ovarian neoplasmsMost common malignant tumor of sex cord-

sromalAssociated with hyperestrogenismMay 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 ovaryAccounts for 25% of all ovarian malignancyMimic primary ovarian cancerPresent as bilateral adnexal masses25% unilateralCommon primary cancers

Breast (40%_Stomach (Krukenberg tumors)Colonendometrium

Diagnosis of ovarian CancerInsidious diseaseNon specific GIT complainsAbdominal distentionPelvic weightMenstrual abnormalities in 15%Rarely excessive estrogens or androgens

ScreeningRoutine pelvic examinationUltrasound examinationTumor markers

CA-125 antigen from fetal amniotic and coelomic epithelium

TAG 72 ,M-CSF ,OVX1

Evaluation of the patient with suspected ovarian neoplasmChild and postmenopausal women at great

risk of malignancyReproductive women is likely to have

functional cyst or endometriomaDifferential diagnosis is influenced by

Age Characteristic of the mass on pelvic

examinationRadiographic appearance

Physical ExaminationComprehensive examination

Lymph node , Sister Mary Joseph’s noduleAbdomen examinationPelvic examination

Characteristics

BenignMalignant

MobilityMobileFixed

ConsistencyCysticSolid or Firm

Bilateral/Unilateral

UnilateralBilateral

Cul-de-sacSmoothNodular

Radiographic EvaluationTrans abdominal ultrasoundTrans vaginal ultrasoundColor flow Doppler

ConsistencySimple cyst <10cm in size

Solid or cystic and solid

SeptationsSeptations <1mm in thickness

Multiple septations >3mm in size

Uni or bilateralunilateralBilateral

othersCalcification, teeth

ascites

Radiographic Evaluation,,,,Computed tomography (CT)

Pelvic organs and Retroperitoneal structuresMagnetic resonance imaging (MRI)

Nature of ovarian neoplasmX ray chestBarium enemamammogram

Laboratory EvaluationCBCSerum electrolyteshCG (pregnancy)AFP ,LDH lactate dehydrogenase (young

girls)CA-125

Surgical Treatment of Epithelial CancerSurgery is the corner stone of therapySurgical staging to

Reduce amount of disease Evaluate the extent of spread

Debulking or cytoreduvtive surgery is removalPrimary tumorAssociated metastasis disease

Intra operative differentiationBenignMalignant

SimpleUnilateralNo adhesionsSmooth surfaceIntact capsule

AdhesionsRuptureAscitesSolid areasAreas of hemorrhage or necrosisMulti loculated massBilateral

Most common location of metastases

Peritoneum 85%Omentum 70%Liver 35%Pleura 33%Lung 25%Bone 15%

Procedures in stagingSample of ascites or peritoneal washings from

Para colic gutters , pelvic and subdiaphragmatic for cytologyComplete abdominal explorationIntact removal of tumorInfracolic omentectomyBiopsies of abdominal peritoneal implantsPelvic and Para aortic lymph node biopsiesCytoreduvtive 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 NeoplasmsMost are at early stage on young womenRemoval of involved adnexiaSame complete surgical staging

Chemotherapy of epithelial cancerStage Ia and grade I, don’t need treatmentAgents ,cisplatin, carboplatin,

cyclophosphamide, paclitaxelCompination 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 NeoplasmsCurableDysgerminoma most radiation sensitivePreserve future reproductive potential with

chemotherapyRegimens ,vinblastine-bleomycin-cisplatin ,

vincristin-actinomycin, D-cyclophsphomide, bleomycin-etoposide-cispltin

Complications of chemotherapyNausea vomiting alopecia

AgentToxicity

CisplatinCarboplatinCyclophosphamidePaclitaxilAltretaminEtoposideBleomycinDoxorubicin Vincristineifosfamide

Nephrotoxicity,neurotoxicity, ototoxicityThrombocytopenia, neutropeniaHemorrhagic cystitis, pulmonary fibrosisMyelosuppressionPeripheral neuropathyMyelosuppressiomPulmonary fibrosisCardiac toxicityNeurotoxicityHemorrhgic cystitis,central neurotoxicity

Radiation therapy and alternativeVery limited role in epithelial cancerDysgerminomaImmunotherapyGen therapy

prognosisRelated to

Response to chemotherapyDifferentiation of tumorGerm cell better than epithelialStage of the disease -5 year survival rate

(epithelial) Stge I -75-93% stageII- 65-74% Stage III- 23-41% Stage IV- 11%