Female Reproductive System Kristine Krafts, M.D. | November 25 , 2013

1. Female Reproductive System Kristine Krafts, M.D. | November 25, 2013

2. Female Reproductive System Outline • Cervix • Uterus • Ovaries • Breast

3. Female Reproductive System Outline • Cervix • Cervical carcinoma

4. Cervical Carcinoma • Once the most common cancer in women – now not even in top 10. • Decrease due to Pap test! • At the same time, precursor lesions are increasing (early detection)

5. Cervical Intraepithelial Neoplasia (CIN) • Precursor to carcinoma • Almost all carcinomas arise in CIN; but not all cases of CIN progress to carcinoma! • Three grades: • CIN I: mild dysplasia (half regress, 20% progress) • CIN II: moderate dysplasia • CIN III: severe dysplasia (30% regress, 70% progress) • The higher the grade, the more likely the lesion will progress to carcinoma

6. Cervical Carcinoma Risk Factors • Early age at first intercourse • Multiple sexual partners • A male partner with multiple previous partners • Persistent infection with “high-risk” HPV • Smoking • Immunodeficiency

7. Cervical Carcinoma and HPV • HPV is detectable in almost all CIN and cancer. • “High-risk” types: • 16, 18, 45, 31 • Found in carcinomas • Integrate into genome, inactivate p53, RB • “Low-risk” types: • 6, 11 • Found in condylomas (benign lesions) • Do not integrate into genome

9. Development of transformation zone

10. Transformation zone Normal cervix, young adult

11. Transformation zone

12. Spectrum of cervical intraepithelial neoplasia (CIN)

13. Normal (left) turning into CIN (right)

16. normal CIN I CIN II CIN III Cytology of CIN (Pap smear)

17. normal CIN I CIN II CIN III “High-grade dysplasia” “Low-grade dysplasia” Cytology of CIN (Pap smear)

18. Invasive Cervical Carcinoma • Most cases are squamous, arising from CIN • Small number are adenocarcinomas • Peak age: 45 (10-15 years after CIN develops!) • Spreads slowly • Most cases are diagnosed early • Mortality is related to stage: • stage 0 (preinvasive): 100% 5 year survival • stage 4: 10% 5 year survival

19. Cervical carcinoma

20. Cervical carcinoma

21. Female Reproductive System Outline • Cervix • Uterus • endometriosis • endometrial hyperplasia • tumors

22. Endometriosis • Location of endometrial glands outside uterus • Usually peritoneum, rarely lymph nodes • Endometrium undergoes cyclic bleeding • Causes scarring, pain, sometimes sterility • How does endometrium get out?

24. Endometriosis in ovary (“chocolate cyst”)

25. Endometrial Hyperplasia • Proliferation of endometrium due to estrogen excess • Risk factors: anovulatory cycles, obesity, estrogen-producing ovarian tumors, exogenous hormone use • Three categories: simple, complex, and atypical • The more severe the hyperplasia, the greater the chance that it will evolve into carcinoma

26. Normal endometrium

27. Simple Complex Atypical Endometrial hyperplasia

28. Leiomyoma • “Fibroid” • Benign tumor of smooth muscle • Common! • Stimulated by estrogen • Menorrhagia, metrorrhagia, or asymptomatic

29. Leiomyosarcoma • Malignant tumor of smooth muscle • Necrotic, with atypical cells and lots of mitoses • Often recur after surgery • Many metastasize, especially to lungs • 5 year survival = 40%

30. Leiomyoma Leiomyosarcoma

31. Leiomyoma Leiomyosarcoma

32. Endometrial Carcinoma • Peak age: 55-65 (not before 40) • Frequently arises in endometrial hyperplasia • Risk factors: obesity, nulliparity, estrogen replacement • Symptoms: leukorrhea, irregular bleeding • Metastasizes late

33. Endometrial adenocarcinoma

34. Female Reproductive System Outline • Cervix • Uterus • Ovaries

35. Female Reproductive System Outline • Cervix • Uterus • Ovaries • Tumors

36. Surface epithelial tumors Germ cell tumors Sex cord-stromal tumors • Cystadenoma • Cystadenocarcinoma • Teratoma • Dysgerminoma • Yolk sac tumor • Choriocarcinoma • Granulosa-theca cell tumor • Sertoli-Leydig cell tumor Origin of Ovarian Tumors

37. Cystadenoma • Benign tumor derived from surface epithelium • Repeated ovulation, scarring, infolding of epithelium leads to cysts, which can undergo neoplastic transformation • Typically large, occasionally bilateral

38. Patient with ovarian cystadenoma

39. Patient with ovarian cystadenoma

40. Ovarian cystadenoma

41. Ovarian cystadenoma

42. Ovarian cystadenoma

43. Teratoma • Benign tumor with differentiation along all three germ cell layers (ectoderm, endoderm, mesoderm) • Usually cystic, with skin inside (“dermoid cyst”) • Sebaceous material, matted hair, teeth, bone… • Malignant variant has immature tissues

44. Teratoma

45. Teratoma

46. Ovarian Cancer • 23,000 new cases / 15,000 deaths in 2007 • 5th commonest, 5th most deadly cancer in women • Danger: no definitive signs until advanced • Peak age: 50 • Most are cystadenocarcinomas

47. Papillary cystadenocarcinoma

48. Papillary cystadenocarcinoma

49. Ovarian Cancer Symptoms • feeling of fullness or bloating • pelvic pain • back pain • abnormal menses Risk factors • nulliparity • family history (BRCA gene mutation) • NOT using oral contraceptives!

50. Ovarian Cancer • Treatment: surgery, radiation, chemotherapy • Prognosis depends on stage • cancer confined to the ovary: 5y survival 70% • cancer through ovarian capsule: 5y survival 13%