Transcript Ovarian Cancer

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)
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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
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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
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Young females (Seminoma in male)
30-40% of germ cell tumors
Unilateral in 85-90%
Solid
 Endometrial sinus tumor
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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
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Very rare in pure form
HCG and AFP are usually elevated
 Choriocarcinoma
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rare germ cell tumor unrelated to pregnancy
Lower elevation HCG
May cause precocious puberty, uterine bleeding or
amenorrhea
 Gonadoblastoma
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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
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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
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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
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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
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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)
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Stge I -75-93%
stageII- 65-74%
Stage III- 23-41%
Stage IV- 11%