Understanding Ovarian Neoplasm: Types, Diagnosis, and Treatment

1. Ovarian Neoplasm卵巢肿瘤 Chen Xiaojun 2011.09 Chen Xiaojun Ob&Gyn Hospital Fudan Uniiversity Obstetrics &Gynecology Hospital Fudan University

2. One single disease or a group of diseases? • A group of diseases • Benign or malignant disease? • Benign, borderline and malignant • Cancer or sarcoma? • Cancer, sarcoma, germ cell tumor… …

3. What we are going to discuss • General principles of ovarian neoplasm • Benign 良性 • Malignant 恶性 • Epithelial ovarian neoplasm 上皮性卵巢肿瘤 • Nonepithelial ovarian neoplasm 非上皮性

4. Key points in the session • Pathological classification of ovarian tumor • Spread pattern and staging of ovarian cancer • Differential diagnosis of benign and malignant ovarian neoplasm • The use of tumor markers in diagnosis of ovarian neoplasm • Principles of primary operation and chemotherapy for ovarian cancer

5. What is ovarian neoplasm? Epithelial tumor 50-70% 上皮性肿瘤 Germ cell tumor 20-40% 生殖细胞肿瘤 Metastatic tumor 5-10% 转移性肿瘤 Sex cord-stromal tumor 5% 性索间质肿瘤

6. Epidemiology • Almost 1/3 of invasive malignancies of the female genital organs • The fifth most common cause of death from malignancy in women. • A woman's risk at birth of having ovarian cancer sometime in her life is 1% to 1.5%, and that of dying from ovarian cancer almost 0.5% • 5 year survival rate : 90% for malignant germ cell tumor; 30-40% for epithelial ovarian cancer

7. Age distribution of ovarian neoplasm • Epithelial ovarian neoplasm • 50-60 y • 绝经后妇女 • Germ cell neoplasm • Under 30 y • 育龄年轻妇女 Epithelial ovarian cancer

8. Brief description Benign-borderline-malignant Mostly sporadic, 5-10% hereditary for malignancies Hard to be detected in early stage, often advanced when symptom appeared Operations being the most effective treatment Chemotherapy greatly improved prognosis of ovarian cancer

9. Etiology & Risk factors --Epithelial ovarian cancer • Most benign and malignant ovarian neoplasm is sporadic, with familial or hereditary patterns accounting for 5% to 10% of all epithelial ovarian cancer.

10. Etiology & Risk factors --Epithelial ovarian cancer • Sporadic ovarian cancer 散发性卵巢癌 • Continuous ovulation 持续排卵 • Early menarche and late menopause • Low parity and infertility • Damage –repair process leading to mutation • Environment • Pollution • Diet

11. Etiology & Risk factors --Epithelial ovarian cancer • Hereditary ovarian cancer 遗传性卵巢癌（5-10% ） • Hereditary ovarian cancers occur 10 years younger than those with nonhereditary tumors • BRCA1, BRCA2 mutation (ovarian and breast cancer) • Hereditary non-polyposis colorectal cancer遗传性非息肉性结直肠癌 (HNPCC) Syndrome (Lynch II syndrome) (multiple site adenocarcinoma)

12. Etiology & Risk factors --Epithelial ovarian cancer Hereditary ovarian cancer • BRCA1 gene mutation + high-risk families= 28% to 44% lifetime risk of ovarian cancer • BRCA2 gene mutation + high-risk families= 27% lifetime risk of ovarian cancer • BRCA1 or BRCA2 mutation= 56% to 87% risk of breast cancer

13. Symptoms----nonspecific 非特异症状 • Benign and early stage malignancy • Always found during physical examination when the mass is small • Benign and Early stage-vague and nonspecific symptoms • Ovary dysfunction-- irregular menses • Mass compression-- urinary frequency or constipation because of mass compression • Mass compression-- Lower abdominal distention, pressure, or pain, such as dyspareunia • Acute symptoms -- pain secondary to rupture or torsion, are unusual

14. Symptoms • Advanced-stage malignancy • symptoms related to the presence of ascites, omental metastases, or bowel metastases • abdominal distention, bloating, constipation, nausea, anorexia 厌食, or early satiety 早饱 • Cachexia 恶病质 • irregular or heavy menses • 70% had abdominal or gastrointestinal symptoms, 58% pain, 34% urinary symptoms, 26% pelvic discomfort

15. Signs • Benign • Pelvic mass with smooth wall • malignant • solid, irregular, fixed pelvic mass • Pelvic floor nodules • upper abdominal mass or ascites

16. Diagnosis • History • Physical examination • Imaging study • Laboratory examination • Cytological examination • Laparoscopic examination and biopsy • Other auxiliary examination needed

17. Diagnosis • Use of oral contraceptives • Pregnancy and breast-feeding history • Previous gynecologic surgery : tubal ligation or hysterectomy • History of ovarian tumor in the family • Previous cancer history • smoking habits • exposures to harmful occupational or environmental substances • History

18. Pelvic examination If the mass is larger than 5cm, is solid rather than cystic, or is bilateral , ovarian cancer may be present. Nodules on the floor of the pelvis indicate ovarian cancer. Diagnosis benign Malignant

19. Image studies Ultrasonography--most ovarian mass>1cm can be found low resistance and pulsatile indexes suggest the presence of a cancerous tumor. X-ray—mature teratoma with bones and teeth CT scan MRI Diagnosis benign malignant

20. Laboratory Tests Serum tumor markers CA125 epithelial ovarian cancer AFP Yolk sac tumor; other germ cell tumor hCGovarian choriocarcinoma Sex hormones sex cord stromal tumor Tests for genetic mutations Microscopic examination of ovarian cancer cells from ascites or pleural effusion Diagnosis

21. CA125---epithelial cancer marker 85% of women with clinically apparent ovarian cancer have increased levels of CA125 (> 35 U/ml). CA125 is not a specific tumor marker as the protein also is increased during other conditions Some ovarian cancers may not produce enough CA125 to cause a positive test result Diagnosis

22. Differential diagnosis

23. Differential diagnosis • Benign ovarian tumor • Physilogical ovarian cyst: follicular cyst; corpus luteum cyst • Inflammatory cyst • Uterine myoma • pregnancy • Ascites

24. Differential diagnosis • Malignant ovarian neoplasms • Endometriosis • Tuberculous peritonitis • Chronic pelvic inflammatory disease • Metastatic ovarian tumor 哑铃状 • Tumor from other pelvic organs What metastatic ovarian cancer might look like

25. Pattern of spread • Transcelomic腹腔内扩散 • The most common and earliest mode of dissemination is by exfoliation of cells than implant along the surfaces of the peritoneal cavity. • Lymphatic 经淋巴转移 • retroperitoneal ( pelvic and paraaortic ) LN spreading is common in advanced- stage disease. • Hematogenous血行转移 • uncommon, lungs and liver is the most common sites

28. Stage I • Tumor limited to ovary • Ia limited to one ovary • Ib limited to both ovary • Ic Ia or Ib +tumor on ovarian surface; tumor rupture; tumor cell (+） in peritoneal fluid or washing

29. Stage II • With pelvic extension • IIa to uterus or fallopian tube • IIbto other pelvic tissue • IIc IIa or IIb +tumor on ovarian surface; tumor rupture; tumor cell (+） in peritoneal fluid or washing

30. Stage III • Peritoneal implants outside pelvic; LN (+); superficial liver metastasis • IIIa microscopic abdominal seeding • IIIb abdominal implants≤2cm • IIIc abdominal implants>2cm; LN(+)

31. Stage IV • With distant metastasis • Tumor cell (+) in Pleural effusion • parenchymal liver metastasis 肝实质转移

32. Complications • Torsion 扭转 • Rupture 破裂 • Infection 感染 • Malignant transformation 恶性变

33. Acute Complications • Torsion 扭转 • Tumor with long pedicel • Middle sized • Without adhesion • Content not evenly distributed • Sudden occurrence of pain after changing of position, defecation or urination • Complicated with nausea or vomiting, even shock • Tenderness of the pelvic mass, most prominent at the pedicle site • Emergent operation is needed • Tumor should be moved with clapping the root of the pedicle • Torsion should not be released before clapping the pedicle

34. Acute Complications • Tumor rupture 肿瘤破裂 • Spontaneous or exogenesis mechanical reasons • Mild or severe abdominal pain • Symptoms and signs of peritoneal irritation • Intraperitoneal bleeding • Preexisted Pelvic mass cloud not be felt or became smaller on pelvic examination • Emergent operation is needed

35. Management • Benign ovarian neoplasm • Cystectomy or salphingo-oophorectomy • Malignant ovarian neoplasm • Complete staging surgery • Fertility preservation surgery for young women • Cytoreductive surgery for advanced stage • Chemotherapy • Radiotherapy

36. Management • Complete staging surgery • Laporotormy--A midline or paramedian abdominal incision is recommended to allow adequate access to the upper abdomen • Laparoscopic operation-- only for early stage ovarian cancer • ·

37. Management complete staging surgery 完全分期手术 • Exploration • Free fluid or peritoneal washings for cytological evaluation • Systematic exploration of all the intra-abdominal surfaces and viscera—clock wise • Biopsy any suspicious areas or adhesions on the peritoneal surfaces; and Random peritoneal biopsy including diaphragm

38. Management complete staging surgery • Operation • Total hysterectomy+ bilateral salpingectomy & oophorectomy (Keep and encapsulated mass intact during removal) • Unilateral salpingo – oophorectomy when fertility preservation is desired in selected patients • Omentectomy • Aortic & pelvic lymph node dissection • Appendectomy when mucinous cancer

40. Management • Indication for fertility preserving operation 保留生育功能手术 The uterus and the contralateral ovary can be preserved when • Young and desires fertility • Stage Ia • Low grade (1 or 2) • No evidence of spread beyond the ovary after a thorough staging laparotomy

41. Management • Cytoreductive surgery 肿瘤细胞减灭术 • Staging surgery • Maximal efforts should be made to remove all gross diseases • Optimal cytoreduction: residual disease <1cm

42. Management • Treatment for borderline ovarian tumor 交界性卵巢肿瘤 • Stage I • Hysterectomy + bilateral salpingo-oophorectomy • Unilateral salpingo – oophorectomy when fertility preservation is desired • Stage II-IV complete staging surgery

43. Pregnancy complicated with ovarian neoplasm 妊娠合并卵巢肿瘤 • Mostly benign • Teratoma • Cystic adenoma • Diagnosed by • Pelvic examination during early pregnancy • Ultrasonography after mid-term pregnancy

44. Pregnancy complicated with ovarian neoplasm • Complication • Abortion • Torsion • Rupture • Abnormal fetal growth • Birth tract obstruction • Fast progression of malignant tumor • Management • Operation after 3 months of pregnancy • Surgery when C-S if found during late term pregnancy

45. Prevention and Screening 预防与筛查 • Sporadic ovarian cancer • Prevention • Child bearing • Oral contraceptive pills

46. Prevention and Screening • Sporadic ovarian cancer • Screening • Ultrasonography + CA125 every 6 months for high risk women • Surgery if tumor >5cm • High alert if enlarged ovary before menarche, after menopause or oral contraceptive pills is taken regularly • Consider laparoscope or laparotomy if pelvic mass can not be diagnosed clearly or no effect after treatment

47. Prevention and Screening • Hereditary ovarian cancer • Genetic counseling and genetic testing for BRCA1and BRCA2. • Screening by transvaginal ultrasonography every 6 months for women wishing to preserve their reproductive capacity • Oral contraceptives for young women before they embark on an attempt to have a family. • Prophylactic bilateral salpingo-oophorectomy for women who do not wish to maintain their fertility

48. Prevention and Screening • Hereditary ovarian cancer • Annual mammographic screening beginning at age 30 years for women having strong family history of breast or ovarian cancer • HNPCC syndrome: be treated as above and undergo periodic screening mammography, colonoscopy,and endometrial biopsy

49. Epithelial ovarian neoplasm上皮性卵巢肿瘤

50. Epithelial ovarian neoplasm Serous 浆液性 endosalpingeal Mucinous 黏液性 endocervical Endometriod内膜样 endometrial Clear-cell 透明细胞 mullerian Brenner 勃勒纳 transitional Undifferentiated 未分化 anaplastic