Immunohistochemistry for FOSB and FOS is a Useful Ancillary Tool in the Diagnosis of Epithelioid Hemangioma but There are Pitfalls in Interpretation Including Expression in Other Vascular Lesions

Int J Surg Pathol. 2023 May;31(3):280-288. doi: 10.1177/10668969221101867. Epub 2022 May 29.


Introduction. Epithelioid hemangioma is a benign vascular neoplasm associated with FOS and/or FOSB protein overexpression detected by immunohistochemistry (IHC). Methods. The aim of our study was to determine the co-expression or independent IHC expression of FOS and FOSB in a cohort of epithelioid hemangiomas. We also included two cohorts of other vascular lesions: papillary endothelial hyperplasia and lobular capillary hemangioma / pyogenic granuloma. Results. We identified 50 cases of epithelioid hemangioma, 84% of which were cutaneous and the remaining involved other anatomic locations. Over two thirds of all cases expressed FOSB (68%; 34/50) while FOS immunoreactivity was identified in 46% of all cases. Co-expression of FOSB and FOS occurred in 37% of cases while 76% of all cases stained for at least one of the antibodies. Fifty-eight percent (n = 14/24) and 33% (8/24) of all cases of papillary endothelial hyperplasia expressed FOS and FOSB, respectively. Thirty-two per cent of lobular capillary hemangiomas (n = 8/25) were positive for either FOS or FOSB. Conclusion. In summary, we present the largest cohort of epithelioid hemangiomas assessed with both FOS and FOSB and demonstrated that the use of both antibodies increases the detection rate of these proliferations by 10%. Nonetheless, the use of thresholds may not be appropriate, as only a subset of lesional endothelial cells label with FOS/FOSB. Over half of all cases of papillary endothelial hyperplasia and a third of lobular capillary hemangiomas also displayed immunoreactivity with FOS and/or FOSB.

Keywords: FOS; FOSB; epithelioid hemangioma; papillary endothelial hyperplasia.

MeSH terms

  • Endothelial Cells / pathology
  • Granuloma, Pyogenic* / pathology
  • Hemangioma* / diagnosis
  • Hemangioma, Capillary* / pathology
  • Humans
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Proto-Oncogene Proteins c-fos
  • Vascular Neoplasms* / pathology


  • FOSB protein, human
  • Proto-Oncogene Proteins c-fos