Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia

Histopathology. 2022 Jan;80(2):369-380. doi: 10.1111/his.14558. Epub 2021 Nov 11.


Aims: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia.

Methods and results: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings.

Conclusions: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

Keywords: MDM2; atypia; atypical lipomatous tumour; lipoma; well-differentiated liposarcoma.

MeSH terms

  • Adult
  • Aged
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lipoma / genetics
  • Lipoma / metabolism*
  • Lipoma / pathology
  • Liposarcoma / genetics
  • Liposarcoma / metabolism*
  • Liposarcoma / pathology
  • Middle Aged
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Retrospective Studies
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology


  • Proto-Oncogene Proteins c-mdm2