Riskfactorsfordevelopingendometrialhyperplasiaincludeanovulatorycycles,polycysticovarysyndrome,estrogen-producingovariantumor,obesity,andestrogentherapywithoutcounterbalancingprogestin.
Hyperplasiaisclassifiedbasedoncytologicatypia,whichdeterminestheriskofdevelopingendometrioidcarcinoma.
Onthebasisofclinicalandmoleculardata,twomajortypesofendometrialcarcinomaarerecognized:
Endometrioid carcinoma isassociatedwithestrogenexcessandendometrialhyperplasia.EarlymolecularchangesincludeinactivationofDNAmismatchrepairgenesandthePTEN gene.
Serous carcinoma oftheendometriumarisesinolderwomenandusuallyisassociatedwithendometrialatrophyandadistinctprecursorlesion,serousintraepithelialcarcinoma.MutationsintheTP53 geneareanearlyevent,usuallybeingpresentinserousendometrialintraepithelialcarcinomaaswellasinvasiveserouscarcinoma.
Stageisthemajordeterminantofsurvivalinbothtypes.Seroustumorstendtomanifestmorefrequentlywithextrauterineextensionandthereforehaveaworseprognosisthanendometrioidcarcinomas.
These polyps are usually sessile and range from 0.5 to 3 cm in diameter. Larger polyps may project from the http://ebooksmedicine.net
Fig.19.12Endometrialcarcinoma.(A)Endometrioidtype,grade1,infiltratingmyometriumandgrowinginaglandularpattern.(B)Endometrioidtype,grade3,hasapredominantlysolidgrowthpattern.(C)Serouscarcinomaoftheendometrium,withpapillaformationandmarkedcytologicatypia.(D)Immunohis-tochemicalstainingshowsaccumulationofp53,afindingassociatedwithTP53 mutation.
endometrial mucosa into the uterine cavity. They are composed of endometrium resembling the basalis, frequently with small muscular arteries. Some glands are normal architecturally, 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.
Although endometrial polyps may occur at any age, they are most common around the time of menopause. Their main clinical significance is that they may produce abnormal uterine bleeding.
Benign tumors that arise from the smooth muscle cells in the myometrium are properly termed leiomyomas, but because of their firmness often are referred to clinically as fibroids. Leiomyomas are the most common benign tumor in females, affecting 30% to 50% of women of reproductive age, and are considerably more frequent in black women. These tumors are associated with several different recurrent chromosomal abnormalities, including rearrangements of chromosomes 6 and 12 that also are found in a variety of other benign neoplasms, such as endometrial polyps and lipomas. Mutations in the MED12 gene, which encodes a component of the RNA polymerase transcription complex, have been identified in up to 70% of leiomyomas. The mechanism by which MED12 mutations contribute to the development of leiomyomas is not presently understood. Estrogens and possibly oral contraceptives stimulate the growth of leiomyomas; conversely, these tumors shrink postmenopausally.
MORPHOLOGYLeiomyomasaretypicallysharplycircumscribed,firmgray-whitemasseswithacharacteristicwhorledcutsurface.Theymayoccursingly,butmoreoftenoccurasmultipletumorsthatarescatteredwithintheuterus,rangingfromsmallnodulestolargetumors(