Abstract

We present the case of a 9 x 6 cm mass on the shoulder of a 35-year-old man. The mass was a seemingly mobile, subcutaneous nodule associated with pain radiating down the arm. The patient had a history of a prior myxoid liposarcoma at another site, as well as a history of with Li-Fraumeni syndrome (LFS). The biopsy revealed an unremarkable epidermis and dermis overlying adipocytes that varied significantly in size. High power examination revealed several large, angulated, hyperchromatic nuclei, some of which were atypical stromal cells. The morphologic features and clinical presentation were consistent with Atypical Lipomatous Tumor/Well Differentiated Liposarcoma (ALT/WDS). Unlike most cases of ALT/WDS, however, the biopsy lacked overexpression of MDM2 and CDK4. Importantly, the absence of those features is expected in patients with LFS; in the rare published cases on ALT/WDS specifically in patients with LFS, that finding is characteristically absent. This absence has been explained by the fact that the germline mutation in p53 has the same biological effect as amplifications in MDM2 and CDK4. Indeed, immunostaining for p53 was entirely negative in this case, reflecting a null phenotype, or a truncating mutation in p53. The absence of MDM2 and CDK4 overexpression by IHC should not rule out a diagnosis of ALT/WDL in patients with LFS, nor should it preclude pathologists from pursuing additional workup in appropriate cases. We review the important features of ALT/WDS, detail the biology of the p53-CDK4-MDM2 interaction, and review the literature on ALT/WDS in hereditary cancer syndromes.

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