38. MDM2/CDK4 amplification in large and/or deep-seated lipomatous neoplasms without overtly atypical morphological features

Abstract

Background MDM2/CDK4 gene amplification has been shown to be sensitive and specific for the diagnosis of well-differentiated lipoma-like liposarcoma (WD-LLLPS). However, there are limited data on the incidence of these alterations in large and/or deep-seated lipomatous neoplasms (LN) in which the histological features do not fulfil criteria for WD-LLLPS. Aims To assess the incidence of MDM2/CDK4 amplification in large and/or deep seated LN without overtly atypical morphological features and to examine the clinicopathological features of cases showing these alterations. Methods All LN submitted for FISH analysis or conventional karyotyping from January 2009 to March 2013 were retrospectively identified from our database. Tumours measuring >50mm in maximum extent and/or in deep-seated locations (excluding retroperitoneal cases) were included. FISH analysis was performed using in-house CDK4/MDM2/CEP12 probes. The clinical, radiological and pathological features of all cases with CDK4/MDM2 amplification were reviewed. Results 81 cases were identified including 51 (63%) males and 30 females (37%) with a median age of 60 years (range 24-83). The most common site was the thigh ( n = 20). FISH analysis was attempted in 77 (95%) cases and karyotyping in 4 (5%). Cytogenetic analysis could not be performed in 4 (5%) cases due to technical factors. Two (3%) cases showed dual MDM2/CDK4 amplification and 2(3%) showed MDM2 amplification alone. All were deep seated with a median size of 95 mm (range 35-160 mm). Two had unusual radiological findings (intermediate signal intensity on MRI). Retrospective slide review confirmed the absence of diagnostic features of WD-LLLPS. Two cases showed marked degenerative changes and one showed prominent lymphocytic inflammation. Conclusions The incidence of MDM2/CDK4 amplification was reassuringly low (5%) in this cohort of LN, despite their large and/ or deep-seated nature. Features that may suggest a potentially more aggressive neoplasm include unusual radiological findings, degenerative changes and prominent inflammation.