February 2022 – Bone and Soft Tissue Pathology

A 64-year-old man presented with an ulcerated lesion on his fifth finger. Biopsy demonstrated epithelioid malignant appearing cells with nuclear expression of ERG, resulting in a diagnosis of “malignant mesenchymal neoplasm” favoring angiosarcoma. Tumor cells also expressed cytokeratin AE1/AE3. Subsequent amputation specimen (Figures 1 and 2) showed an infiltrative neoplasm composed of malignant epithelioid cells, focally forming pseudovascular spaces. Immunohistochemistry for INI-1 showed loss of nuclear expression. AE1/AE3 was positive and repeated IHC for ERG was negative.

Figure 1
Figure 2

Which of the following statements are true regarding epithelioid sarcoma? 

  • Epithelioid sarcoma shows a predilection for bone metastases.
  • Epithelioid sarcomas may mimic granulomatous inflammatory processes.
  • Most epithelioid sarcomas harbor deletions in the SMARCA4 gene.
  • Approximately 50% of epithelioid sarcomas express CD31.

The correct answer is ...

Epithelioid sarcomas may mimic granulomatous inflammatory processes.

Epithelioid sarcomas may mimic granulomatous inflammatory processes, in part due to an interstitial growth pattern of tumor cells that often show limited cytologic atypia, and thus may be prone to misinterpretation as histiocytes. Additionally, there may be necrosis similar to what may be seen in infectious processes. Epithelioid sarcomas show a predilection for lymph node metastases (not bone metastases). The majority (approximately 95%) of epithelioid sarcomas harbor genetic deletions of SMARCB1, and loss of INI1 expression in tumor cell nuclei is often used as a surrogate marker for this event. By contrast, SMARCA4 gene deletions are seen in fewer than 5% of epithelioid sarcomas, and loss of BRG1 nuclear expression can be used as a surrogate. Finally, CD34 expression occurs in approximately 50% of epithelioid sarcomas. ERG expression can also be seen in up to 40% of cases. Expression of these markers may lead to a misinterpretation as angiosarcoma, particularly when combined with a pseudovascular morphologic pattern. However, CD31 (a relatively specific vascular marker) is consistently negative in epithelioid sarcomas.


  1. Oda, Y., Nielsen, T.O., Dal Chin, P., et al. World Health Organization Classification of Tumours, Bone and Soft Tissue Tumours, 5th ed. 2020. International Agency for Research on Cancer. 33, 127.

Suzanna Logan, M.D., Ph.D.

Fellow, Bone and Soft Tissue Pathology
Mayo Clinic

Ray Guo, M.D., Ph.D.

Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Assistant Professor of Dermatology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.