Ovarian Cancer
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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)
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%