Histopathological Correlation of Chromosome 12 Polysomy by Fluorescence in Situ Hybridization in Adipocytic Neoplasms

Abstract

Background: Identification of MDM2 amplification by fluorescence in situ hybridization is an important diagnostic tool for evaluation of adipocytic neoplasms. Rarely, neoplasms can show increased copies of MDM2 and CEP12 probes (polysomy) without amplification ( MDM2/CEP12 ratio <2.0). While noted in the literature, this finding has not been the focus of any study to date. Methods: Consecutive cases were retrospectively screened for increased copies of MDM2 and CEP12 and were classified as: high polysomy (ratio<2.0, CEP12≥10.0), low polysomy (ratio<2.0, but >0.5, CEP12≥4.0 but <9.9), and CEP12 amplification (ratio≤0.5, CEP12 > 4.0). H&E slides were classified by a pathologist into diagnostic categories based on morphology without knowledge of MDM2 amplification result. Correlations between chromosome 12 polysomy and histological features in the same region of the tumor were investigated. Results: There were 19 (0.7%) high polysomy, 52 (2.0%) low polysomy and 3 (0.1%) CEP12 amplification cases identified in the 2541 cases screened. While low polysomy was seen across benign and malignant adipocytic tumors and other sarcomas, high level polysomy was primarily seen in liposarcomas, both atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS). No lipomas were high polysomy. Conclusion: Polysomy is an uncommon, but distinct, finding in adipocytic neoplasms found across the spectrum of benign to malignant with little insight into the pathophysiology or prognosis. While low polysomy is also observed in benign adipocytic neoplasms, high polysomy is almost always seen in malignant adipocytic neoplasms and is uncommon in benign adipocytic neoplasms.