2. Female Reproductive System Outline Ovaries Disorders of Gestation

3. Polycystic Ovary Disease Formerly Stein-Leventhal syndrome affects 3% to 6% of reproductive-age women. The central pathologic abnormality is numerous cystic follicles often associated with oligomenorrhea: persistent anovulation, obesity (40%), hirsutism (50%), and, rarely, virilism

4. Polycystic Ovary Disease Morphology The ovaries are usually twice normal size and have a smooth, gray-white outer cortex studded with subcortical cysts 0.5 to 1.5 cm in diameter. On histologic examination, there is a thickened, fibrotic superficial cortex beneath which are innumerable follicle cysts associated with hyperplasia of the theca interna (follicular hyperthecosis

5. Polycystic Ovary Disease Etiology Unclear, due to dysregulation of several enzymes involved in androgen synthesis Increased secretion of luteinizing hormone may contribute to excessive production of androgens by the theca lutein cells. The excessive androgens are converted to estrone. Insulin resistance is an additional features usually seen. Treatment: of the insulin resistance sometimes results in resumption of ovulation.

6. Ultra sound “ Strings of pearl”

7. Ovarian Tumours Divided into: The surface müllerian epithelium The germ cells The sex cord-stromal cells.

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

9. Ovarian Tumours Ovarian epithelial tumors are divided into Serous, mucinous and endometriod types based on histology. These are further divided based on extent of epithelial proliferation into: Benign, Borderline,Malignant Benign tumors in younger age group Borderline and Malignant in older age group 90 % of ovarian tumors 80% are benign

10. Ovarian Tumours Ovarian epithelial tumors are divided into Serous, mucinous and endometriod types based on histology. These are further divided based on extent of epithelial proliferation into: Benign, Borderline,Malignant Benign tumors in younger age group Borderline and Malignant in older age group 80% are benign The malignant epithelial derived tumors constitute more than 80% of all malignant ovarian tumor.

11. Ovarian Tumours Serous tumor Most common histologic type(tall cilliated columnar epithelium with watery secretions(fallopian tube like epitheliu) Bilateral tumors are relatively common BRCA-1,BRCA2,P53 BRAF,KRAS mutations Benign Serous adenoma, Serous cystadenoma, Malignant Serous cystadenocarcinoma(most common malignant ovarian tumor,40%) Omental and peritoneal spread =>ascites

12. Ovarian Tumours Mucinous Tumors KRAS mutation Most are unilateral tumors Areas of solid growth correlate with increase chances of malignancy Tall,columnar, mucin secreting epithelial lining(endocervical like epithelium). Huge tumors(larger than serous tumors)More likely benign than malignant. Dissemination into the peritoneum may lead to pseudomyxoma peritonei. Note that metastatic spread from appendiceal tumor may also present with P.Myxoma Peritonei.

13. Ovarian Tumours Endometriod tumors Glandular epithelium similar to uterine endometrium Most are carcinomas(malignant) Associated with PTEN,B-catenin pathway mutation and p53 mutation 20% 0f cases coexist with endometriosis,15-30% have an associated endometrial carcinoma.

14. Ovarian Tumours Endometriod tumors Glandular epithelium similar to uterine endometrium Most are carcinomas Associated with PTEN,B-catenin pathway mutation and p53 mutation 20% 0f cases coexist with endometriosis,15-30% have an associated endometrial carcinoma.

15. Ovarian Tumours Brenner tumors Adenofibromas of the ovary Fibrous stroma and epthelial component that shows a transitional type differentation(Bladder like epithelium) Most are benign and non functional.

16. Ovarian Tumours;Diagnosis and clinical features Most ovarian tumors present late CA125 is marker present in 80% of Ovarian CA. It lacks specificity and may be elevated in other conditions of ovarian inflammation such as endometriosis. CA 125 is more useful for monitoring tumor remission in patient undergoing treatment. OCPS and bilateral tubal ligation has shown remarkable reduction in ovarian CA risk.

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

18. Ovarian Cancer 23,000 new cases / 15,000 deaths in 2007 5 th commonest, 5 th most deadly cancer in women Danger: no definitive signs until advanced Peak age: 50 Most are cystadenocarcinomas and sometimes shows Psamomma bodies. Risk of malignancy increases with :Bilaterality,Increase in solid areas,presence of of complex atypia and endometriod histology.

19. Papillary cystadenocarcinoma

20. 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%

21. Patient with ovarian cystadenoma

22. Ovarian cystadenoma

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

25. Ovarian tumors Ovarian germ Cell Tumors Similar to MGT, Germ cell tumors Patients are younger compared to epithelial tumor(reproductive age) Most common is Benign teratomas Malignant germ cell tumors account for 5% of all ovarian cancers.

26. 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(immature neuroepithelium) Monodermal teratoma includes struma ovarii and ovarian carcinods. Rarely teratomas undergo malignant transformation(squamous, thyroid carcinoma)

27. 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(immature neuroepithelium),uncommon,seen in prepurtal Monodermal teratoma includes struma ovarii and ovarian carcinods. Rarely teratomas undergo malignant transformation(squamous, thyroid carcinoma)

28. Teratoma

30. Dysgerminoma Analogous to Seminoma in males Always malignant but variable degree of aggressiveness Chemo and radio sensitive(>80% survival) Morphology: large cell cells with clear cytoplasm dispersed in sheets of or cords with scanty fibrous stroma.

31. Yolk Sac Tumor Similar to the male counterpart Alpha feto protein and alpha-1 antitrypsin may be positive Extra embryonic differentiation Malignant tumor children and young women. Morphology; Schiller duval bodies,(central blood vessel enveloped by germ cells within a space lined by germ cells.(said to resemble primitive looking glomerulus)

32. Schiller –Duval Body

33. Choriocarcinoma Most are mixed tumors Trophoblastic differentiation of germ cells Poorer response to chemotherapy compared to Gestational Choriocarcinoma Elevated Beta HCG

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

35. Ovarian stroma tumors Granulosa –Theca cell tumor Fibro-Thecomas

36. Granulosa –Theca cell tumor Estrogen producing tumors, may lead to uterine hyperplasia, precocious puberty Risk of malignancy 5-25 % 2 components granulosa and theca,the granulosa component is responsible for estrogen as well as the risk of malignancyy Cells recapitulating ovarian follicles, Call - Exner bodies may be seen. The tumor produces Inhibin.

37. Granulosa –Theca cell tumor Estrogen producing tumors, may lead to uterine hyperplasia, precocious puberty Risk of malignancy 5-25 % 2 coponents granulosa and theca,the granulosa component is responsible for estrogen as well as the risk of malignancyy Cells recapitulating ovarian follicles, Call - Exner bodies may be seen. The tumor produces Inhibin.

38. Call-Exner Bodies

39. Fibrothecomas Composed of fibroblasts or lipid producing cells Common,4 % of ovarian tumors. Most are unilateral tumors and are benign Meigs syndrome(Ascites,right sided hydrothorax,ovarian tumor) Gorlin syndrome(Basal cell nevus syndrome)

40. Sertoli-Leydig (Androblastomas) Causes masculinizaton due to excessive androgen Hirsuitism,breast atrophy,masculine voice,(defeminization) Embryogensis is unclear

41. Secondary tumors Mullerian derived tumors(uterus, fallopian tube, pelvic peritoneum) Krukenberg tumors from gastric(signet ring type),sometimes breast Pseudo myxoma peritonei from appendiceal tumors(rare)

42. Diseases of Pregancy Gestational Trophoblastic diseases

43. Gestational Trophoblastic Disease 1. Complete mole 2. Partial mole 3. Invasive mole 4. Gestational Choriocarcinoma

44. Hydatidiform mole A hydatidiform mole is an abnormality of fertilization It is the result of fertilisation of anucleated ovum ( has no chromosomes) with a sperm which will duplicate giving rise to 46 chromosomes of paternal origin only. It is the result of fertilisation of an ovum by 2 sperms so the chromosomal number is 69 chromosomes COMPLETE MOLE PARTIAL MOLE

45. Complete mole:

46. (ii) Partial mole

47. Grapelike hydrropic chorionic villi

48. Hydatidiform Mole, complete mole. No maternal tissues.

49. Partial mole This is a partial mole that occurs when two sperms fertilize a single ovum. The result is triploidy (69 XXY). Only some of the villi are grape- like, and a fetus can be present, but rarely survives past 15 weeks.

50. S & S Hydatiform Mole Vaginal bleeding  anemia  uterus size, cramps No FHT’s   Nausea/Vomiting Early PIH Elevated B-hcg.

51. Hydatidiform Moles Risk of malignancy Complete Mole 2.5% increased risk of choriocarcinoma. No significant risk of choriocarcinoma in partial moles.

52. Hydatidiform Moles Investigation: B-Hcg Histology : Complete mole; All or most of the villi are involved. The chorionic villi are enlarged,shows central cavitations and lack well developed blood vessels)There is extensive proliferation of trphoblasts. Partial mole; Villous enlargement,architectural changes and trophoblast proliferation are seen in only portions of the chorionic villi.

53. Hydatidiform Moles Investigation: P57 immunostaining may be used to differentiate complete from partial moles in equivocal cases. (+ve in partial moles but absent in complete moles ).The p57 gene is present in maternal tissues but absent in paternally derived chromosomes due to genomic imprinting.

54. Invasive Mole Invasive hydatidiform mole Invasive hydatidiform mole (complete or partial) is common since molar trophoblast invades the myometrium in most cases. Confirmed both on ultrasound examination of the uterus and the hCG profile in patients following evacuation of the uterine cavity. May spread to lungs and brain but do not grow in these organs(not true metastasis) Elevated B-HCG Irregular bleeding,and uterine enlargement. Chemotherapy..good cure rates.

55. Gestational Choriocarcinoma Choriocarcinoma is a tumour composed both of cyto-trophoblastic and syncitio- trophoblastic cells. Widespread intravascular dissemination to lungs, brain and other sites. Good response to chemotherapy compared to ovarian choriocarcinoma. The presence of paternal DNA is thought to elicit an immune reaction which contributes to elimination of the tumor

56. Gestational Chorio carcinoma Origin: 50% arise in complete hydatidiform moles, 25% in previous abortions, 22% in normal pregnancies 3% occurs following ectopic pregnancy

57. Gestational Chorio carcinoma Histology: Mixed proliferation of syncytio and cytotrophoblast without chorionic villi.

58. B-HCG elevation Choriocarcinoma>Invasive Mole>Complete mole>Partial mole>Normal pregnancy>Ectopic pregnancy

59. Hypertensive disease of Pregnanacy Pre-eclampisa,Eclampsia and HEELP syndrome

60. Hypertensive disease of Pregnanacy Pre-eclampisa: Elevated blod pressure Proteinuria Pedal edema 1 st pregancies 6% of pregnancies Requires monitoring blood pressure control and delivery ASAP

61. Hypertensive disease of Pregnanacy Pathogenesis of Pre-eclampsia Thought to be caused by placenta ischemia

62. Hypertensive disease of Pregnanacy Clinical 32 nd week Hypertension,edema,proteinuria,headeach e Bed rest,anti-hypetensives and delivery are the cure Resolves within 2 weeks of delivery.

63. Hypertensive disease of Pregnanacy Eclampsia Syndrome of eclampsia with addition of seizures Carries a very high mortality rate

64. Hypertensive disease of Pregnanacy HEELP syndrome Hemolysis Eclampsia Elevated liver enzymes Low Platelets