A single institutional experience treating adipocytic tumors: Incidence, disease-related outcomes, and the clinical significance of mdm2 analysis

Abstract

Adipocytic tumors exist either as a benign or malignant form. The benign vari-ant, lipoma, is composed of normal fat tis-sue. Lipomas typically develop from super-ficial fat cells beneath the skin or mucous membranes. Liposarcoma, the malignant counterpart, often develops in deeper tis-sues and is the most commonly diagnosed Soft Tissue Sarcoma (STS), comprising at least 20% of adult STS. However, malignant tumors of fatty origin exist as a spectrum of diagnoses, each carrying a unique risk of recurrence, metastasis, and long-term survival. The World Health Organization classifies liposarcomas into five categories: i) Atypical Lipomatous Tumors/Well Differentiated (ALT/WD); Ii) Dedifferentiated (ALT/DD); Iii) Myxoid; Iv) Round cell; and v) Pleomorphic. Lipomatous tumors often exhibit different immunohistochemical patterns. Benign lipomas are distinguished by the absence of Murine Double-Minute 2 (MDM2) amplifi-cation. Similarly, ALT/WD, classically defined as a low-grade and locally aggressive tumor, demonstrates consistent patterns of MDM2 amplification. Some studies suggest 10% of ALT/WD progress to the high-grade DD form, with others report a dedif-ferentiation rate of as high as 20% for primary ALT/WD based on location. The ALT/DD subtype is aggressive and has a high capacity to metastasize. While the mechanism of pathogenesis of ALT/DD metastasis is unknown, previous studies suggest that increased MDM2 amplification may play a role. This study sought to eval-uate a single institutional experience treating the entire spectrum of lipomatous tumors and describe utilization patterns of-MDM2 testing. The group hypothesized: i) Atypical Lipomatous Tumors (ALT), which include ALT/DD and ALT/WD, would exhibit a higher rate of local recurrence than lipomas with no significantly increased incidence of metastases; and ii) at least 50% of our MDM2 testing of ALT would prove positive for the MDM2 overamplification. This study retrospectively reviewed 105 cases (66 lipomas, 27 ALTs, 12 liposarco-mas) of patients who underwent lipomatous tumor excision at our institution from 2013 to 2017. Twenty-five tumors (6 lipomas, 18 ALT, 1 liposarcoma) were tested for MDM2 amplification. Three of the tested tumors recurred (2 ALT, 1 liposarcoma), and each exhibited MDM2 overamplification. Five tumors (5 liposarcoma) developed late metastases. These data suggest that although ALT is associated with a higher rate of local recurrence, metastases are quite rare. Additionally, the data demonstrate a high rate of positive MDM2 testing (76%) based on clinical and imaging characteristics of the tumors.