p16 Expression in Fat Necrosis: A Potential Diagnostic Pitfall in the Evaluation of Differentiated Adipocytic Neoplasms

Int J Surg Pathol. 2015 Oct;23(7):544-8. doi: 10.1177/1066896915595465. Epub 2015 Jul 14.


Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories. p16 immunohistochemistry is a sensitive marker for WDL and is in the repertoire of most laboratories, and it has been suggested as a useful method of distinguishing WDL from lipomas when other ancillary modalities are not readily available. We describe a case of a large retroperitoneal adipocytic mass occurring in a 27-year-old male, which was clinically and radiologically in keeping with WDL. Histologically this was a differentiated adipocytic neoplasm with prominent fibrous septa and fat necrosis, more suggestive of retroperitoneal lipoma. Immunohistochemistry showed diffuse, strong nuclear expression of p16 in the areas of fat necrosis. However, CDK4 was negative and the lesion lacked evidence of MDM2 amplification with FISH. Diffuse expression of p16 in areas of fat necrosis in large or deep lipomas highlights the potential for diagnostic misinterpretation as well differentiated liposarcoma, and we therefore emphasize that p16 immunohistochemistry should always be interpreted as part of a panel with CDK4 +/- MDM2 in the differential diagnosis of WDL and lipoma.

Keywords: CDK4; MDM2; atypical lipomatous tumor; fat necrosis; immunohistochemistry; lipoma; p16; retroperitoneum; well-differentiated liposarcoma.

Publication types

  • Case Reports

MeSH terms

  • Adipocytes / pathology*
  • Adult
  • Biomarkers, Tumor / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Diagnosis, Differential
  • Gene Amplification
  • Humans
  • Lipoma / diagnosis*
  • Lipoma / genetics
  • Lipoma / pathology
  • Liposarcoma / diagnosis*
  • Liposarcoma / genetics
  • Liposarcoma / pathology
  • Male
  • Prognosis
  • Retroperitoneal Neoplasms / diagnosis*
  • Retroperitoneal Neoplasms / genetics
  • Retroperitoneal Neoplasms / pathology


  • Biomarkers, Tumor
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4