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MALIGNANT DISORDERS OF THE OVARIES

MALIGNANT DISORDERS OF THE OVARIES. Assoc. Prof. Gazi YILDIRIM, M.D. Yeditepe University, Medical Faculty Dept of Ob&Gyn. The 5. most common cancer in women The 5. most frequent cause of cancer death Lifetime risk 1/70. 5-year survival rate <35% Mortality has decreased only

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MALIGNANT DISORDERS OF THE OVARIES

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

  2. The 5. most common cancer in women • The 5. most frequent cause of cancer death • Lifetime risk 1/70

  3. 5-year survival rate • <35% • Mortality has • decreased only • slightly in 30 years • Most diagnosis • made at advanced • disease

  4. RISK FACTORS • Cause of Ovarian Cancer is unknown Risk Factors • High socio-economicstatus • Early menarche • Late menopause • Few children • Never used oralcontraceptive • Genetic (10%) • Environment??? • Dietary factors • Exposure to talc • Exposure to asbestos >90% of ovarian cancer develops sporadically. ~10% of epithelial ovarian cancers are based on genetic predisposition.

  5. GENETIC PREDISPOSITION • Chromosomal abnormalities • Turner syndrome Dysgerminoma, gonadoblastoma • Hereditary ovarian cancer • BOC (breast and ovarian cancer syndrome) • BRCA-1 mutations on chromosome 17 and less commonly BRCA-2 mutations on chromosome 13. • Lynch II syndrome (HNPCC syndrome) • DNA mismatch repair gene mutations • Colon ca, ovarian-endometrial-breast cancer • Acquired genetic abnormalities • P53 tumor supressor gene mutations, HER2/neu proto-oncogene activation

  6. Genetic Predisposition: 5-10% 0f Ovarian Cancer • Carriers of BRCA1 orBRCA2: • 40% risk of ovariancancer • BRCA1 and 2 Germ linemutations: • 10% of all ovariancancers • 1-2% of all breastcancers

  7. HISTOPATHOLOGY OF OVARIAN CANCER 5% of ovarian cancer arises from metastases!! (breast, colon, stomach, endometrium, lymphoma)

  8. EPITHELIAL NEOPLASMS • Derived from the ovarian surface mesothelial cells. • Serous • Mucinous • Endometrioid • Clear cell • Transitional cell • Undifferentiated • Account >60% of all ovarian neoplasms and >90% of malignant ovarian tumors.

  9. Serous Neoplasms • Most common malignant tumor of the ovary. • 35-50% of all epithelial tumors. • Bilateral in 40-60 of cases. • Extraovarian spread at the time of diagnosis in 85% of cases. • Cut section: solid areas,areas of hemorrhage,necrosis, cyst wall invasion and adhesions to adjacent structures.

  10. Histology- serous carcinoma • Mild to moderate nuclear atypia • Psammoma body (irregular calcifications) • The grade of differentiation is based on the degree of preservation of the papillary architecture.

  11. Mucinous Neoplasms • Account for 10-20% of all epithelial ovarian neoplasms • The second most common type of epithelial ovarian cancer. • Bilateral in <10% of cases (in contrast to serous tumors!!!!)

  12. Large size (~16 cm) • Cut sections: multilocular cysts filled with viscous mucin.

  13. Histology- mucinous carcinoma • Composed predominantly of intestinal-like cells that invade surrounding stroma. • Invasive tumors exhibit marked histologic variability from area to area within the tumor. • The differentiation is based on the preservation of the glandlike architecture of the tumor. Extensive sampling required !!

  14. Pseudomyxoma peritonei • Resulting from the progressive accumulation of mucin in the abdominal cavity. • Most commonly in association with low malignant potential. • Also with cystadenocarcinoma of the ovary and appendix, mucocele of the appendix. *potentially morbid secondary to repeated bowel obstruction.

  15. Endometrioid Neoplasm • Exhibits an adenomatoid pattern that resembles endometrial adenocarcinoma. • Bilateral in 30-50% of cases. • Arises rarely in foci of endometriosis (<10% of cases). • The degree of differentiation is based on the extent to which the glandular architecture is retained. • In 30% of cases, there is a synchronous endometrial carcinoma of the uterus A second primary rather than a metastatic focus !!!

  16. Clear Cell Carcinoma • Also referred to as mesonephroid carcinoma • Biologically aggressivehypercalcemia and hyperpyrexia • Difficult to differentiate from mucinous neoplasms the periodic acid-Schiff reaction only weakly (+) in clear cell carcinoma; strikingly (+) in mucinous tumors.

  17. Transitional Cell (Brenner) Carcinoma • Composed of cells that resemble low-grade transitional cell carcinoma of the urinary bladder. • Typically diagnosed at advanced stage disease • Poorer prognosis when compared with that of other histologic types of epithelial ovarian cancer.

  18. Undifferentiated Carcinoma • <10% of epithelial neoplasms. • Characterized by the absence of any distinguishing microscopic features that permit its placement in one of the other histologic categories.

  19. GERM CELL NEOPLASMS • Arise from the germ cell elements of the ovary. • Dysgerminoma • Endodermal sinus tumor • Embryonal cell carcinoma • Choriocarcinoma • Teratoma • Polyembryoma • Mixed germ cell tumors • Occur during the second and third decades of life. • Produce biologic markers which can be monitored to assess response to therapy.

  20. Tumor Markers that may be elevated in the presence of Germ Cell Neoplasms

  21. Dysgerminoma • The female counterpart of the seminoma in the male. • Young females • 30-40% of germ cell tumors. • Unilateral in 85-90% of cases.

  22. Endodermal Sinus Tumor • Second most common germ cell tumor (20%). • Bilateral in <5% of cases. • The most rapidly growing neoplasm !! • Commonly present with an acute abdomen. • Pathognomic finding: Schiller-Duval body • AFP(+)

  23. Immature Teratoma • The malignant counterpart of the mature cystic teratoma or dermoid. • 20% of germ cell tumors. • Bilateral in <5% of cases, although the contralateral ovary commonly contains a dermoid cyst • Immature elements: commonly neuroectodermal

  24. Mature Teratoma (Dermoid) • Common • 20-30 years • The most common tumor diagnosed during pregnancy. • Rarely, the squamous component undergoes malignant transformation over the age 40. (<2%)

  25. Embryonal Carcinoma • Younger patients (mean age of 14 years) • Epithelial cells resembling those of the embryonic disc. • Typically produce hCG • 75% also secrete AFP.

  26. Choriocarcinoma • Primary ovarian choriocarcinoma arises from a germ cell similar in appearance to gestational choriocarcinoma. Nongestational tumors: poorer prognosis * The detection of other germ cell components indicates nongestational tumors!

  27. Gonadoblastoma • Rare tumor composed of nests of germ cells and sex cord derivatives. • More common in the right ovary. • Usually during the second decade of life. • Found in patients with abnormal gonadal development in the presence of a Y chromosome.

  28. Mixed Germ Cell Tumors • 10% of germ cell neoplasms. • Contain ≥2 germ cell elements. • Dysgerminoma and endodermal sinus tumor occur together most frequently.

  29. SEX CORD-STROMAL TUMORS • Heterogeneus group of rare neoplasms originating from the ovarian matrix. cells within matrix have potential for hormon production. Signs and symptoms of estrogen or androgen excess.

  30. Granulosa Cell Tumors • 1-2% of all ovarian tumors. • The most common malignant tumors of the sex cord-stromal tumors. • Hyperestrogenism • Call-exner bodies Precocious puberty in young girls Endometrial hyperplasia and vaginal bleeding in postmenopausal women

  31. Thecoma • Benign • Hyperestrogenism • Lipid-laden stromal cells • Typically develop in postmenopausal women in their mid-60s. Yellow color on cut section

  32. Fibroma • Benign • Meigs’ Syndrome • Ovarian fibroma • Ascites • Pleural effusion • Hormonally inactive Mimic the presentation of ovarian cancer.

  33. Sertoli-Leydig Cell Tumors • Rare • Consist of testicular structures at different stages of development. • Usually virilizing • During the third decade of life • Rarely bilateral

  34. Tumors metastatic to the ovary • 25% of all ovarian malignancies. • Clinically mimic the primary ovarian cancer • Usually present as bilateral adnexal masses • 25% of cases unilateral • Most common primary cancers: breast, stomach, colon and endometrium.

  35. SYMPTOMS • Vague and non-specific !! • Abdominal bloating • Indigestion, dyspepsia • Altered bowel habits • Menstruel abnormalities • Pelvic fullness • Pain

  36. Evaluation of the patient with a suspected ovarian neoplasm

  37. The prepubertal child and the postmenopausal woman are at greatest risk for developing a pelvic mass that subsequently proves to be a malignant ovarian tumor. The reproductive age woman is more likely to have a functional ovarian cyst or endometrioma.

  38. Physical Examination • Perform a comprehensive examination. • Attention to the lymph-node-bearing areas • Particularly the supraclavicular and inguinal areas. • Examination of the abdomen • Abdominal distention • The presence of flank fullness and shifting dullness • Tympanitic percussion note over the lateral abdomen a large mass displacing the bowel to the periphery. • central tympanitic percussion note ascites

  39. Characteristics of a pelvic mass on physical examination BENIGN !! Mobile Cystic Unilateral Cul-de-sac: smooth MALIGNANT !! Fixed Solid or form Bilateral Cul-de-sac:nodular

  40. Radiographic Evaluation-I • Ultrasonography • Transabdominal • Transvaginal • Color flow doppler studies • CT retroperitoneal structures,pelvic organs • MRI more information regarding the nature of the ovarian tumor. • High cost and questionable benefit !!! • Particular benefit in the evaluation of pregnant woman.

  41. Radiographic Evaluation-II • Radiograph of the chest exclude metastatic parenchymal disease and detect pleural effusion. • Barium enema • Screening mammogram study

  42. Radiographic characteristics that help to differentiate benign and malignant adnexal masses BENIGN *Simple cyst, <10 cm in size *Septations, <3 mm in thickness *Unilateral *Calcification, especially teeth *Gravity-dependent layering of cyst contents MALIGNANT *Solid or cystic+solid *multiple septations >3mm in size *bilateral *ascites

  43. PROGNOSTIC FACTORS • Stage !! • Grade • Cell-type of tumor • Residual disease aftersurgery • Disease volume prior to any surgical debulking • Age of woman >70 • Performance status

  44. SCREENING FOR OVARIAN CANCER NO EVIDENCE THAT SCREENING WORKS!! • Ultrasound • Transvaginal • Abdominal • Color flow • Tumor Markers: • Ca 125 • Protein patterns • Pelvic exam • Genetic screening

  45. SURGICAL TREATMENT of epithelial overian cancer • Surgery:the cornerstone of therapy • debulking: • remove as much ofthe cancer as possible • the less cancer leftafter primary surgerythe better theoutcome • the best outcome iswhen there is noresidual disease

  46. At the time of diagnosis, >70% of patients with epithelial ovarian cancer have metastases beyond the pelvis • . The most common locations of metastases: *peritoneum (85%) *omentum (70%) *liver (35%) *pleura (33%) *lung (25%) *bone (15%) Lymphatic metastasis occurs frequently, with up to 80% involving pelvic lymph nodes and 67% involving para-aortic lymph nodes, depending on the stage of cancer.

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