Multifocal neoplasia involving the colon and appendix in ulcerative colitis: Pathological and molecular features

A patient with ulcerative colitis, extensive dysplasia, multifocal colon ca ncer, and an appendiceal cystadenoma is described. A 48-year-old man with a 26-year history of ulcerative colitis (UC) had extensive dysplasia involvi ng nearly the entire colon and four dysplasia-associated mass lesions (DALM s), Four invasive adenocarcinomas were present. This case is the first docu mentation of a DALM (mucinous cystadenoma) arising in the appendix in the s etting of UC. The genetic alterations present in the various lesions were a nalyzed, The molecular profiles of the neoplastic lesions differed. Mutatio ns were found in p53 and ras genes, and one site showed microsatellite inst ability in a single genetic locus, These molecular abnormalities develop be fore invasive cancer develops, and may undergo clonal expansion to create l arge mucosal patches containing certain cells with genetic alterations, The diversity of the early changes suggests that the recurrent inflammation ch aracteristic of long-standing UC randomly damages genes known to participat e in colon carcinogenesis and that it affects multiple target genes, The fi ndings also support a multiclonal origin of synchronous tumors because the molecular phenotypes of the preinvasive lesions differed at various sites.