Ovarian Cancer

Deri Edianto

Greatest clinical challenge. Epithelial are most common cases with advanced disease No screening method Major surgical challenge 90% from celomic epithelium

Histologic typing of epithelial ovarian carsinoma

Serous type : 40 50% Mucinous type : 12 15% Endometrioid type : 25% Clear cell Malignant Brenner Undifferentiated carsinomas

Borderline tumor
Low malignant potential Remain confined to the ovary Good prognosis Metastatic implants may occur

Etiology : ?

Variety of epidemiologic variables Low parity and infertility Talc use : Tubal ligation : Oral contraceptive 5 years : Genetic ( 5 10% ) Early menarche and late menopause

Prevention : oral contraceptive

Screening :

Tumor marker : ? Ultrasonography (transvaginal) Gynecologic examination

Not cost effective

Hereditary ovarian cancer

Accounting 5 10% Most are sporadic BR CA1 mutation : chromosome 17 BR CA2 mutation : chromosome 13 Ovarian and breast cancer HNPCC (Lynch II) Autosomal dominant 10 year younger than sporadic

Symptom and sign

No symptom for long period Often vague and nonspecific Mass compressing symptom Pelvic mass on physical examination Solid, fixed, irregular Ascites

Diagnosis

Requires an exploratory laparotomy Frozen section Paraffin block

Differential diagnosis

Benign neoplasm Functional cyst Non gynecologic

Patterns of spread
Cell exfoliation Peritoneal cavity: tanscelomic Lymphatic dissemination Hematogenous spread

Prognostic factors
1. Pathologic hystologic type : clear cell grade 2. Biologic ploidity : aneuploid HER 2 neu expression 3. Clinical stage residual mass age

Staging

Tumor confined to the ovaries IA tumor limited to one ovary, capsule intact . No tumor on ovarian surface. No malignant cells in the ascites or peritoneal washing. IB tumor limited to the both ovaries, capsule intact. No tumor on ovarian surface. No malignant cells in the ascites or peritoneal washing. IC tumor limited to one or both ovaries, with any of following: capsule rupture, tumor on ovarian surface, positive malignant cells in the ascites or peritoneal washing. II Tumor involve one or both ovaries with pelvic extension. IIA extension and/or implants in uterus and/or tube. No malignant cells in the ascites or peritoneal washing. IIB extension to other pelvic organ. No malignant cells in the ascites or peritoneal washing. IIC IIA/B with positive malignant cells in the ascites or peritoneal washing

Staging
III Tumor involve one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvic and /or regional lymph node metastasis

IIIA IIIB IIIC

microscopic peritoneal metastasis beyond the pelvis macroscopic peritoneal metastasis beyond the pelvis 2cm or less in greatest dimension peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension and/or regional lymph node metastasis

IV Distant metastasis beyond the peritoneal cavity

Surgery

Staging Fluid : cytologic examination Peritoneal washing Systematic abdominal exploration Biopsy at any suspicious areas Omentum resection Lymph node evaluation TAH + BSO Conservative : I A + preserve fertility Debulking or cytoreductive surgery

Rationale for cytoreductive

Physiologic benefit Improve tumor perfusion Increase growth fraction Enhance immunologic

Physiologic benefit
Reduce ascites volume Alleviate nausea and satiety Restore intestinal function Improve nutritional status

Tumor perfusion

Bulky tumor : poor vascularisation Chemotherapy concentration Poorly oxygenated

Growth fraction

Non dividing / resting phase (G0) Resistant to the therapy Fractional cell kill hypothesis

Immunologic

Large mass immunosuppressive Host defense mechanism Cytotoxic lymphocyte

Adjuvant therapy
No adjuvant Chemotherapy Radiation Hormonal Immunotherapy

No adjuvant

Stage I A grade 1 Stage I A I B grade 1 & 2 Non high risk

Chemotherapy

High risk Combination Cisplatin base Cisplatin + paclitaxel Intravenous Intraperitoneal : ? Neoadjuvant Interval debulking

Radiation

Whole abdomen Some institution in Canada Not been tested against chemotherapy

Hormonal
Not appropriate as primary therapy Progestional agent Recurrent case For : well differentiated endometrioid (+) ve estrogen receptor

Immunotherapy

Various trial Corynebacterium parvum Bacillus Calmette Guerin (BCG) Conjunction with cytotoxic chemotherapy Benefit : ? Cytokine, interferon, interleukin Monoclonal directed antibody Herceptin : HER 2 / neu

Nonephitelial ovarian and Fallopian tube cancer

Uncommon ( 10%) Germ cell origin Sex cord stromal origin Metastasis carcinoma Sarcoma Fallopian tube carcinoma

Histologic typing of ovarian germ cell tumors

Dysgerminoma Teratoma

A. mature B. immature

solid Cystic

C. monodermal and highly specialized

Dermoid cyst (mature cystic teratoma) Dermoid cyst with malignant transformation

Endodermal sinus tumor Embryonal carcinoma Polyembrioma Choriocarsinoma Mixed form

Struma ovarii Carcinoid Struma ovarii and carsinoid Others

Epidemiology
Only 10% are malignant More frequent in Asian and black women First two decade of life

Symptom and sign

Grow rapidly (than epithelial) Hemorrhage and necrosis Pressure symptom to bladder/rectum May torsion or rupture Palpable adnexal mass Ascites at advanced cases

Diagnosis

Premenarchal girl : 2 cm Premenopausal : 8 cm Tumor marker : hCG & AFP Karyotype evaluation (dysgenetic gonad = Y chromosome)

Dysgerminoma

Most common germ malignant Younger age (10 30 years) Rarely after 50 years Always in stage I Young women : complete surgery ? Conservative surgery Chemo and radiosensitive With Y chromosome : BSO

Radiation

Very sensitive 2.500 3.500 cGy Loss of fertility Rarely use as first line therapy

Chemotherapy

The treatment of choice Preservation of fertility Cisplatin based combination

Recurrent disease

Most in the first year Depend on first treatment Chemo or radiation Relaparotomy : later

Immature teratomas
Resemble tissue derived from embryo Combination with other germ cell Malignant transformation from mature teratoma is rare Usually unilateral

Diagnosis

Same as other germ cell

Treatment

Surgery Fertility preserve : conservative surgery No fertility need : complete surgical Chemotherapy : initiated a s a p Except : stage IA grade 1 Radiation : not as primary treatment

Endodermal sinus tumor (EST)

Referred as yolk sac carsinomas Derived from primitive yolk sac Abdominal / pelvic pain Most secrete AFP

Treament
Surgery Fertility can be preserved Chemotherapy : all patients

Embryonal carsinoma

Extremely rare tumor Very young ( 4 20 years) May secrete estrogen : pseudopuberty Frequently secrete AFP and hCG Treatment : same as for EST

Choriocarsinoma of the ovary

Pure non gestational Extremely rare Secrete hCG Chemotherapy same as gestational

Sex cord stromal tumors

Derived from sex cord and ovarian stroma Composed various combination Female cells : granulosa and theca cell Male cells : Sertoli and Leydig

Treatment

Surgery Chemo and radiation : ?

Fallopian tube cancer

Only 0,3% of female genital tumor Feature and behavior = ovarian cancer Exclusively or predominantly involve the fallopian tube Treatment = epithelial ovarian cancer