1. Endometrial polyp, hyperplasia, carcinoma Dr: Salah Ahmed

2. Endometrial polyps - are focal benign overgrowth of endometrium - most common located on the fundus - may protrude into vagina and may cause bleeding

3. Endometrial polyp ( fibrous stroma harboring dilated glands lined by columnar epithelium

4. Endometrial hyperplasia - exaggerated endometrial proliferation due to excess of estrogen - can be preneoplastic - hyperplasia is classified based on crowding of glands and presence of atypia into: 1- simple hyperplasia 2- complex hyperplasia 3- atypical hyperplasia - these changes depend on the level and duration of the estrogen excess - risk factors: (estrogen excess) 1- failure of ovulation (e.g around the menopause) 2- prolonged administration of estrogen 3- estrogen-producing ovarian lesions (polycystic ovaries) 4- cortical stromal hyperplasia 5- granulosa-theca cell tumors of the ovary 6- obesity ( because adipose tissue processes steroid precursors into estrogens)

5. A) Simple hyperplasia - crowding of glands without atypia some of them are dilated (cystic hyperplasia) :Swiss cheese - only 1% of cases progress to adenocarcinoma

6. B) Complex hyperplasia - crowding and branching of glands without cellular atypia - 3% of cases progress to adenocarcinoma

7. C) Atypical hyperplasia - complex hyperplasia with atypia ( hyperchromatic nuclei, mitotic figures ) - commonly progresses to adenocarcinoma - treated may be with Tamoxifen (antiestrogen) or hysterectomy

8. Endometrial carcinoma - endometrial carcinoma is the most frequent cancer of the female genital tract Epidemiology and Pathogenesis: - common between the ages of 55 and 65 years - arises in two clinical settings: 1- in perimenopausal women with estrogen excess (endometrioid carcinoma) 2- in older women with endometrial atrophy (serous carcinoma) - Pathogenesis: 1) Endometrioid type: - related to excess of estrogen - the risk factors: 1- nulliparity 2- early menarche or late menopause 3- obesity (increased synthesis of estrogens )

9. 4- Diabetes Hypertension Infertility: women tend to be nulliparous, often with anovulatory cycles. 5- prolonged estrogen replacement therapy 6- estrogen-secreting ovarian lesions 7- endometrial hyperplasia - genetic abnormality: 1- mutations in DNA mismatch repair gene 2- mutations in PTEN, a tumor suppressor gene 2) Serous type: - is a distinct type - It typically arises in a background of atrophy - sometimes arises in endometrial polyp - nearly all cases have mutations in the p53 tumor suppressor gene

10. Morphology: - Endometrioid carcinomas: - closely resemble normal endometrium - may be exophytic or infiltrative - may infiltrate the myometrium and enter vascular spaces, with metastases to regional lymph nodes - four stages: stage I: confined to the corpus stage II: involvement of the cervix stage III: beyond the uterus but within the true pelvis stage IV: distant metastases or involvement of other viscera - Serous carcinoma: - forms small tufts and papillae rather than the glands - has much greater cytologic atypia - They behave as poorly differentiated cancers and are aggressive

11. (A, B )Endometrioid carcinoma (C ) Serous carcinoma of the endometrium displaying formation of papillae and marked cytologic atypia (D )Immunohistochemical stain for p53 reveals accumulation of mutant p53 in serous carcinoma.

12. Clinical course:- first clinical indication is marked leukorrhea and irregular bleeding - With progression, the uterus becomes enlarged and fixed - metastases to cervix, tubes, ovaries, vagina, broad ligament, regional LN, lungs, liver

13. Thank you