Chapter 21 Female Genital Tumor

1. Chapter 21 Female Genital Tumor 6. Ovarian Tumor Women’s Hospital, School of Medicine, Zhejiang university Xiaodong Cheng

2. Ovarian tumor • Common gynecologic malignant tumors • Occur in females of all ages • but different histological types in different age-periods • Epithelial ovarian carcinoma with poor prognosis 5-year survival rate about 30-40% the mortality rate ranks first in gynecological malignancies

3. General Introduction • Histological classification very complicated • Most histological types in body organs • The current classification issued by WHO in 1973

4. Histologic types of ovarian tumor • Ovarain epithelial tumor • Germ cell tumor • Sex-cord stromal cell tumor • Lipid (lipoid) cell tumor • Gonadal blastoma • Non-specific ovarian soft tissue tumor • Unclassified tumor • Metastatic tumor • Tumor-like lesions

5. Symptoms and signs • Benign tumors • No symptoms as tumor is small • Abdominal distention or pelvic mass as tumor is medium size • Gynecological examinations A spherical mass on one side of the uterus, cystic, smooth surface, movable

6. Symptoms and signs • Ovarian cancer • early stage asymptomatic, often found occasionally by gynecological examinations • Late stages Abdominal distention, abdominal mass, ascites • End-stage Weight loss, severe anemia, cachexia Transvagina-rectnum examination • Pelvic masses: bilateral , solid or semi-solid, not movable

7. Complications • pedicel retortion Common gynecological emergency • Frequency about 10% • Usually occur in mass with a longer pedicle, medium size, good movability, and center deflection • Blood flow blocked and tumor necrosis after retortion Symptoms: one side of lower abdomen pain concomitant nausea and vomit, Signs: Mass with high tension and tenderness Treatment emergency surgery once diagnosed

8. Complications • Rupture • Frequency about 3% • Traumatic and spontaneous • Symptom lower abdominal pain related to the size of rupture the quality and quantity of cyst fluid • Signs abdominal tenderness muscle intensity ascites • Treatment emergency surgery

9. Complications • Infection • Due to rupture, retorsion or the near organs’ infection • Symptoms fever, abdominal pain • Signs mass, abdominal tenderness, muscle intensity • Treatment anti-infection, surgery • Malignant change surgery as soon as possible

10. Diagnosis • Benign tumors No specific symptoms A mass found occasionally by physical examination • Ovarian cancer No specific symptoms Gynecological examination bilateral pelvic mass, solid , poor movability, with ascites, uterus rectum nest nodules

11. Diagnosis • Adjuvant examinations Imaging techniques • Ultrasonography ： mainly used to diagnose primary lesion accuracy rate above 90% difficult to measure the diameter <1cm lesion • Radiology (X-Ray, CT, MRI) mainly used to diagnose the metastatic lesion

12. Ultrasound: ovarian cancer

13. Diagnosis • Adjuvant examinations • Tumor markers §CA125 rise up in 80% epithelial cancers more used for disease monitoring and prognosis evaluation §AFP rise in endodermal sinus tumor §hCG ovarian choriacarcinoma §Sex hormone sex-cord stromal cell tumor • Laparoscopy • Ascitic cytology

14. Metastatic pathway • Features • Widely disseminated in abdominal cavity • Subclinical metastasis • pathways • spread directly and abdominal cavity plant • lymph metastasis • blood vessel metastasis

15. Clinical surgical-pathology staging (2000，FIGO)

16. Therapy • Surgery Objectives • To confirm the diagnosis • To resect tumor • To determine surgical-pathology staging of malignancy • Chemotherapy and radiation for malignancy • follow-up ovarian cancer is easy to recurrent and should be long-term follow-up

17. Epithelial tumors • The most common histological type accounting for 50-70% of the primary tumor 85-90% of malignant tumor • Derived from ovarian germinal epithelium belong to the primitive body cavity epithelium have potential to differentiate into a variety of Mullerian epithelia • More common in older women • Can be divided into benign, borderline, malignant tumors

18. Epithelial tumors • Borderline tumors • low malignant potential tumors • pathological features of malignant tumor cells but no stromal invasion • clinically slower development, fewer metastasis and more later recurrence

19. Histological classification Epithelial tumors • Serous tumors • Mucinous tumors • Endometrioid tumor • Brenner tumor • Mixed epithelial tumors • Undifferentiated carcinoma Changing: New classification—2014 (WHO)

20. Pathology Serous tumors cancer cell differentiate into oviduct epithelial • Serous cystadenoma Mostly unilateral, spherical, smooth, cystic, serous fluidMicroscope: simple columnar epithelium • serous cystadenocarcinoma Mostly bilateral, semi-substantive, multiple antrum cystoid, cavity filled with papilla, crisp, bloody cyst fluid Microscope: cubic or columnar epithelium, stratified, arranged in ≥4 layers, cellular atypia, stromal invasion

21. Serous tumors Serous cancer

22. Pathology Mucinous tumors cancer cell differentiate into enteric or cervical endometrial • Mucinous cystadenoma Mostly unilateral, large size, cystic, and often have more capsules with the jelly-like mucus Microscope:simple columnar epithelium, can see goblet and argyrophil cells If tumor rupture, tumor cells seed in peritoneal to form peritoneal myxoma • Mucinous cystadenocarcinoma Mostly unilateral, cystic, cystic see the papilla, bloody cyst fluid Microscope:columnar epithelium, stratified, arranged in ≥ 3 layers, cellular atypia, stromal invasion

23. Mucinous tumors Mucinous cancer

24. Pathology • Endometrioid tumor • Benign, borderline tumor is few • Endometrioid carcinoma • Mostly unilateral, cystic or solid, with papilla, bloody cyst fluid. Microscope: similar to endometrial cancer • Often concomitant with endometrial cancer

25. Endometrioid cancer

26. Pathology Clear cell tumors • Benign tumors are few • Clear cell carcinoma • Mostly unilateral, cystic or solid • Microscope:alveolar tumor cells with abundant cytoplasm , atypia nuclear • Easy to lymph node and liver metastasis • Often concomitant with endometriosis and hypercalcemia • Brenner tumor • Differentiate and formate from transitional epithelum • Most are benign, unilateral, diameter <5cm, hardware quality

27. Clear cell tumors

28. Brenner tumor

29. Epithelial Tumors Treatment • benign tumors • Once diagnosed, surgical extension • reproductive period women ovarian tumor resection or oophorectomy perimenopausal and postmenopausal women ● adnexectomy ● hysterectomy and bilateral salpingo-oophorectomy Notices in surgery ① differentiate the benign and malignant tumors during surgery (grossly, frozen section ) ② take out the tumor integrally

30. Epithelial Tumors Treatment • malignancy • Principle: surgery combined with chemotherapy and radiotherapy • surgery Early stage: Staging surgery • Cytology for ascites or peritoneal washings • Complete pelvic and abdominal exploration • Omentectomy • Back peritoneum lymph nodes excision • Hysterectomy + bilateral salpingoophorectomy • Conservative surgery only for eligible young women desiring childbearing

31. Epithelial Tumors Treatment • malignancy • surgery Advanced stage: Cytoreductive surgery (debulking surgery) Resect primar and metastatic tuomrs as much as possible , to minimize diameter of residual tumor (<1cm)

32. Epithelial Tumors • Chemotherapy Major adjuvant therapy, post-surgery Commonly used drugs cisplatin, carboplatin, paclitaxel, CTX, others. Preferred to platinum-based combination chemotherapy “Gold standard”: carboplatin and paclitaxel combination • Radiotherapy For metastasis and recurrence • Others immunotherapy Prognosis 5-year survival rate of Ia stage >90％ 5-year survival rate of advanced stage <30％

33. Ovarian germ cell tumor Features • From primitive germ cells in embryonic gonad • Ability to produce diversity organizations • Frequency: account for 20~40% in all ovarian tumors • More common in young women and girls • Sensitive to chemotherapy ，most can be reserved for reproductive function • Abnormal tumor markers: AFP, HCG

34. Histologic classification Germ cell tumors • dysgerminoma • endodermal sinus tumor • embryonal tumor • polyembryoma • choriocarcinoma • teratomas • mixed tumor

35. Pathology Teratomas • Comprised of multi-germ layer , rarely one layer • Mostly are mature , few are immature • Mature teratomas（dermoid cyst） • benign tumor，the most common germ cell tumor • frequently single side, cystoid with smooth surface, contains tissues of fat, hair, teeth and bone • microscopy： scolex contains three layers • malignant transformation: squamocarcinoma in scolex epilithium

36. Mature Cystic Teratoma Immature ovarian teratoma

37. Pathology Dysgerminoma • Moderate malignant tumor • Mostly occurs at puberty and child-bearing perild • Single side, solid • Microscopy ：rotundity or mostly cornual cells • Extraordinary sensitive to radiotherapy

38. dysgerminoma

39. Pathology Endodermal sinus tumor • Common in children and young women • Highly malignant, poor prognosis • Single side with large mass, fragile, obvious bleeding and necrosis; • Microscopy：loose reticulate and endothelial sinus structure • Produce AFP

40. Endodermal sinus tumor

41. Treatment • Benign tumor The same as epilithial tumors • Malignant tumor Surgery Lateral salpingoophorectomy regardless any stage as long as opposite side ovary and uterus are not involved Chemotherapy Sensitive to chemotherapy : BEP BVP VAC Radiotherapy sensitive for Dysgerminoma，seldom used for young ages

42. Sex cord-stromal tumors • From sex cord and stromal tissues of embryonic gonad • Frequency: account for 5％ in all ovarian tumors • Comprised or uni- or multi-cell components • Mostly are benign or low malignant tumor • Produce steroid hormones, with endocrine funtion, produce female or male features, also called “functioning ovarian tumor ”

43. Histologic classification Sex cord-stromal tumors • Granulosa cell -stromal cell tumors • Sertoli-stromal cell tumors • Granudroblastoma

44. Pathology Granulosa cell tumors • Adult form and child form • Adult form • common • low malignant，produce E2，female features • solid or partly cystic • microscopy: Granulosa cell, Call-Exner body • Child form • seldom, highly malignant

45. Granulosa cell tumor Granulosa cell tumor Call–Exner bodies (sex cord-stromal tumors ) Granulosa cell tumor Granulosa cell tumor stromal cell tumors

46. Pathology Ovarian thecoma (theca cell tumor) • Benign，seldom malignant • Single side, solid. • Microscopy short spindle cells, spiral arrangement • Female features

47. Ovarian thecoma

48. Pathology Fibroma • Benign • Single side, solid, hardness • Microscopy short spindle cells, knitting arrangement. • Meigs syndrome fibroma combination with ascites or hydrothorax, naturally disappear after tumor excision

49. Fibroma

50. Treatment • Benign tumor surgery as same as epithelial tumor • Malignant tumor Surgery Conservative surgery for young women with stage I, desiring childbearing Radical surgery for others Chemotherapy Combinated Chemotherapy Regimens: as same as germ cell or epilithelial tumors