Atypical Pleomorphic Lipomatous Tumor: Expanding Our Current Understanding in a Clinicopathologic Analysis of 64 Cases.

Atypical pleomorphic lipomatous tumor (APLT) is a recently recognized adipocytic neoplasm that lies on a spectrum with atypical spindle cell lipomatous tumor (ASCLT). APLT/ASCLT are included together in the fifth edition World Health Organization Classification of Soft Tissue and Bone Tumours; however limited data on APLT have emerged since its first description in 2017. This study aims to further define the clinicopathologic features of APLT in a large series of 64 cases. Histologic features and ancillary studies were reviewed, and clinical and follow-up data were obtained from referring institutions. Immunohistochemistry for MDM2, CDK4, CD34, Rb, S100, and desmin was performed in cases with available material. Patients were 24 females and 40 males, and the median age was 61 years (range, 20 to 89 y). Tumors arose in upper limb (33%), lower limb (31%), trunk (23%), head and neck (8%), breast (3%), and inguinal region (2%), with a median size of 5.4 cm (range, 1.5 to 14.5 cm). Tumor depth was mostly subcutaneous or deep/subfascial. Microscopically, APLTs were variably composed of atypical spindle and pleomorphic cells, adipocytes, and lipoblasts, often showing infiltrative growth, myxoid or collagenous stroma, and multinucleate floret cells. Mitoses were infrequent and necrosis was consistently absent. By immunohistochemistry, tumors expressed CD34 (63%), S100 (19%), and desmin (28%). APLT showed frequent loss of Rb (79%; 46/58). Rare cases showed staining for MDM2 (2%) or CDK4 (12%); however, fluorescence in situ hybridization was negative for MDM2 amplification in all cases tested (0/22). Follow-up in 28 patients (median duration: 21 mo) revealed a single patient with local recurrence (4%); no patient developed metastatic disease. Despite its frequently infiltrative growth, nuclear pleomorphism, and hypercellularity which can mimic sarcoma, APLT behaves in an indolent manner and should be distinguished from its more aggressive mimics, including atypical lipomatous tumor/well-differentiated liposarcoma and pleomorphic liposarcoma. Immunohistochemistry for CD34, S100, desmin, and Rb (demonstrating loss), as well as exclusion of MDM2 amplification, can support the diagnosis.