MALIGNANT DISORDER OF THE UTERINE CORPUS

1. MALIGNANT DISORDER OF THE UTERINE CORPUS Assoc. Prof. Gazi YILDIRIM, M.D. Yeditepe University, Medical Faculty Dept of Ob&Gyn

2. Endometrial Carcinoma • The most common pelvic genital cancer in women. • White woman have 2.4% risk of endometrial carcinoma (Black woman 1.3%) • The peak incidence in the 7th decade • characterised by hyperplasia and anaplasia of the glanduler elements, with invasion of underlying stroma, myometrium and vascular spaces

3. Risk Factors • Long term exposure to unopposed estrogens • polycystic ovarian syndrom • chronic anovulation • obesity • Early menarche • late menopause • exogenous estrogens) • Metabolic syndrome including diabetes, hypertension • Nulliparity • Increasing age • History of breast cancer • genetic predisposition • (hereditary nonpolyposis colon cancer syndrom) (HNPCC syndrom)  MSH2, MLH1, Ha-, K-, N-ras, c-myc, Her-2/neu, alterations in p53

4. ETIOLOGY • Type I Endometrial carcinoma • Associated with either endogenous or exogenous unopposed estrogen exposure • low grade or well differentiated tumor with favourable prognosis. • Type II Endometrial carcinoma • Independent of estrogen • Associated with endometrial atrophy • High risk of relapse with poor prognosis.

5. CLINICAL FINDINGS • Abnormal bleeding 80% of patients Most important and early symptom • Menorrhagia • Metrorrhagia • Postmenopausal bleeding • Lower abdominal cramps and pain 10% of patients It is secondary to uterine contractions caused by blood trapped behind a stenotic cervical os

6. LABORATORY FINDINGS • Rutin laboratory are usually normal • Anemia may be present • Pap smear • CA 125

7. SPECIAL EXAMINATIONS • main examination: endometrial sampling Fractional curretage Endometrial biopsy • Pipelle, novac curet, vabra aspirator • Pelvic ultrasonography • In postmenopausal woman endometrial thickness of more than 5 mm is considered to be suspicious for hyperplasia or malignancy • Estrogen and progesteron receptor assays • In general patiens with tumors positive for one or two receptors have longer survival than patients with receptor-negative tumors

8. CLASSIFICATIONS-1 • Adenocarcinoma • The most common type (80%) • Adenocarcinoma with squamous differantitation • Serous carcinoma • identical to the serous carcinoma of ovary • 1-10% • Woman with serous carcinoma are more likely to be older and less likely to have hyperestrogenic states • spread early and involve peritoneal surfaces of the pelvis

9. CLASSIFICATIONS-2 • Clear cell carcinoma • 1% of all endometrial carcinomas • Microscopic significance: clear cells or hobnail cells • Solid, papillary, tubular and cystic patterns • Commonly high grade and aggresive with deep invasion • older woman (average age: 67 years) • not associated with hyperestrogenic state.

10. Route of Metastasis • Direct extension • Lymphatic metastasis • Peritoneal implants after transtubal spread • Hematogenous spread.

11. Prognostic factors • Stage • Histologic grade • Cell type • Depth of myometrial invasion • Presence of lymphovascular space involvement • Lymph node status • Involvement of the lower uterine segment • Size of tumor • Tumor ploidy and the proportion of cells in S phase as determined by DNA flow cytometry

12. Endometrium Kanseri Cerrahi Evrelemesi (FIGO2009) Evre1 : tm uterus korpusuna sınırlı G1 2 3 1a: myometrial invazyon yok veya <1/2’den az 1b: myometriumun =>1/2’si invaze Evre2: uterus korpusunu ve servikal stromayı tutar,uterusu aşmaz Evre3: pelvise rejyonel tm yayılımı 3a:seroza ve/veya adnekslere invazyon 3b: vajinal ve/veya parametrial metastaz 3c: pelvik ve/veya para-aortik lenf nodu metastazı 3c1: pelvik lenf nodu metastazı 3c2: para-aortik lenf nodu metastazı var, pelvik lenf nodu metastazı var veya yok Evre4: ilerlemiş pelvik hastalık veya uzak metastaz 4a:mesane ve/veya barsak mukozasında tümöral tutulum 4b: intraabdominal ve/veya inguinal lenf nodlarını içeren uzak metastazlar

13. TREATMENT • Surgery • Radiation therapy • Hormone therapy • Chemotherapy

14. SURGERY • The most important treatment modality total simple or radical hysterectomy, bilateral salpingooopherectomy staging, including pelvic and periaortic lymphadectomy

15. Surgical Staging • who requires surgical staging? • Patients with stage I disease with grade 3 lesions • Tumor greater than 2 cm in maximum dimension • Tumors with greater than 50% myometrial invasion • Cervical extention • Evidence of extrauterine spread • Clear cell and papillary serous carcinomas because of high incidence of lymphatic spread

16. RADIATION THERAPY • primary therapy in patients considered to be medically unstable for laparotomy • Adjuvant preoperative radiation is no longer used unless the patient presents with gross cervical involvement • Relative contraindications presense of pelvic mass, a pelvic kidney, pyometra, history of a pelvic abscess, prior pelvic radiation previous multiple laparotomies

17. HORMONE THERAPY • Progesteron has shown some efficacy in the treatment of recurrent endometrial carcinoma not amenable to irradiation or surgery. • In patients with well differentiated estrogen receptor-positive tumors tamoxifen has been used either alone or in combination with progesterons.

18. CHEMOTHERAPHY • Doxorubicin, cisplatin, taxol. • Doxorubicin  single agent response rate 38% • Doxorubicin + cysplatin  longer survival • Taxol + doxorubicin+ cisplatin  response rate 57%

19. Uterine Sarcomas • Four categories; • leiomyosarcomas(LMSS) • endometrial stromal sarcomas (ESSS), • malignant mixed mesodermal tumors (MMMTS) • adenosarcoma