Pilomatrixoma : Molecular Pathology
Activating mutations in CTNNB1 gene coding for beta-catenin appear to play a key role in the pathogenesis of pilomatrixoma. Role of beta-catenin: Beta-catenin is a dual function protein. It is involved in cell-cell adhesion by binding to alpha-catenin as well as cadherins, thereby linking actin cytoskeleton with adherens junctions. It also acts as a signal transducer in Wnt/wingless signal transduction pathway and mediates transcriptional activation of genes such as c-myc and cyclin D1. Regulation of beta-catenin is accomplished by phosphorylation of its N-terminus followed by ubiquitin-mediated degradation involving the adenomatous polyposis coli (APC) protein, encoded by the tumor suppressor APC gene. Beta-catenin mutations in pilomatrixoma: Activating mutations in beta-catenin have been identified in the N-terminus which prevent its phosphorylation leading to accumulation of cytosolic beta-catenin. Pilomatrixoma has been induced in a mouse model by creating truncating mutations in the N-terminus of beta-catenin protein. Beta-catenin in other cancers: Besides pilomatrixoma, mutations in beta-catenin gene have also been found in other morphologically similar tumors, including basal cell carcinoma with ghost cell differentiation, cribriform trichoblastoma, and craniopharyngioma. Other cancers associated with beta-catenin mutations include hepatocellular carcinoma, colorectal cancers, lung cancer, breast carcinoma, ovarian and endometrial cancers. Beta-catenin alterations have also been implicated in dilated cardiomyopathy. The image shows a sheet of basaloid cells and lobules of ghost cells with foreign body giant cell response in a pilomatrixoma.