Endometrial polyp, hyperplasia, carcinoma

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Proliferative lesions of ENDOMETRIUM

Endometrial polyp, hyperplasia, endometrial carcinoma, leiomyoma & leiomyosarcoma.Dr Mohammad Manzoor MashwaniAll tend to produce abnormal uterine bleeding as their earliest manifestation.

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Endometrial PolypsUterine polyp is clinical term used for a polypoid growthprojecting into the uterine lumen and may be composed ofbenign lesions (e.g. endometrial or mucous polyp,leiomyomatous polyp and placental polyp), or malignantpolypoid tumours (e.g. endometrial carcinoma, choriocarcinomaand sarcoma). The most common variety, however,is the one having the structure like that of endometrium andis termed endometrial or mucus polyp.

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

Although endometrial polyps may occur at any age, they most commonly are detected around the time of menopause.Their clinical significance lies in abnormal uterine bleeding and, more important, in the risk (howeverrare) of giving rise to a cancer.

Endometrial PolypsThese sessile, usually hemispheric lesions range from 0.5 to 3 cm in diameter. Larger polyps may project from the endometrial mucosa into the uterine cavity.Small endometrial polyps generally remain asymptomatic and are detectedincidentally.The larger ones may ulcerate, degenerate and result in clinical bleeding

MorphologyGrossly, endometrial polyps may be single or multiple, usually sessile and small (0.5 to 3 cm in diameter) but occasionally they are largeand pedunculated.Have 2 patterns localised polypoid tumour, or a diffuse tumour; the latter being more common. The tumour protrudes into the endometrial cavity as irregular, friable and grey-tan mass. Extension of the growth into the myometrium may be identified by the presence of soft, friable and granular tissue in cut section. In advanced disease, the involvement may extend beyond the physiologic limitsinto the cervical canal, into the peritoneum, besides lymphatic metastases and haematogenous metastases to distant sites such as lungs, liver, bones and other organs.

MorphologyOn histologic examination, they are composed of endometrium resembling the basalis, frequently with small muscular arteries. Some glands have a normal endometrial architecture, but more often they are cystically dilated. The stromal cells are monoclonal, often with a rearrangement of chromosomal region 6p21, and thus constitute the neoplastic component of the polyp.

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

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- Ovarian cortical stromal hyperplasia 5- granulosa-theca cell tumors of the ovary 6- obesity ( because adipose tissue processes steroid precursors into estrogens)Polycystic ovarysyndrome(PCOS), also called hyperandrogenic anovulation (HA), orSteinLeventhal syndrome, is a set of symptoms due to a hormone imbalance in women.

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

Swiss cheese

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

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

When hyperplasia with atypia is discovered, it must be carefully evaluated for the presence of cancer and must be monitored by serial endometrial biopsies.In time, the hyperplasia may proliferate autonomously, no longer requiring estrogen, and eventually may give rise to carcinoma. In a significant number of cases, the hyperplasiais associated with inactivating mutations in thePTEN tumor suppressor gene, an important brake on signalingthrough the PI-3-kinase/AKT signaling pathwayAcquisition of PTEN mutations is believed to be one ofseveral key steps in the transformation of hyperplasias toendometrial carcinomas, which also often harbor PTENmutations.Phosphatase and tensin homolog(PTEN) is aproteinthat, in humans, is encoded by thePTENgene.

Endometrial carcinoma - endometrial carcinoma is the most frequent cancer of the female genital tractEpidemiology 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: 80% - related to excess of estrogen - the risk factors: 1- nulliparity 2- early menarche or late menopause 3- obesity (increased synthesis of estrogens )

In the United States and many other Western countries,endometrial carcinoma is the most frequent cancer occurring in the female genital tract. In Asia Cervical cancer common.These tumors are designated endometrioid because of their histologic similarity to normal endometrial glands. UTERINE CANCER

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: 15% - 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

Cowden syndrome(also known as "Cowden's disease," and "Multiple hamartoma syndrome"[ is a rareautosomal dominantinherited disordercharacterized by multiple tumor-like growths calledhamartomasand an increased risk of certain forms ofcancer (Endometrium, Breast, Thyroid). It is associated with mutations inPTEN, atumor suppressorgene

Whereas the decline in the incidence of cervicalcancer in the developed countries is due to aggressive cervicalscreening programme leading to early detection and cure ofin situ stage, increased frequency of endometrial carcinomain these countries may be due to longevity of womens lifeto develop this cancer of older females.

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

They include a range of histologic types, includingthose showing mucinous, tubal (ciliated), and squamous(occasionally adenosquamous) differentiation. Tumors originatein the mucosa and may infiltrate the myometrium andenter vascular spaces. They may also metastasize to regionallymph nodes. Endometrioid carcinomas are graded I to III,based on the degree of differentiation.

Endometrial carcinoma. The most common histologic pattern is well-differentiated adenocarcinoma showing closely packed(back-to-back) glands with cytologic atypia.

(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.

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

These tumors usually are slow to metastasize, but if left untreated, eventually disseminate to regional nodes and more distant sites. With therapy, the 5-year survival rate for early-stage carcinoma is 90%, but survival drops precipitously in