Abstract

We present the case of a 69-year-old female patient who presented with a subcutaneous nodule on the right knee of unknown duration. Histologic examination of the excision specimen revealed small epithelioid cells arranged in nests and cords within a myxoid stroma. The tumor cells were positive for S100 protein and negative for SOX-10, p63, TCK, CKAE1/3, CK5/6, CK7, CK20, CD45, CD99, EMA, myogenin, and synaptophysin. Next generation sequencing detected an ACTB::GLI1 fusion transcript. Taking together the cytomorphological features, immunohistochemical profile, and results of the molecular study, the tumor was classified as a malignant epithelioid neoplasm (MEN) with glioma-associated oncogene 1 (GLI1) gene rearrangement.

GLI1 is a transcription factor in the Hedgehog signaling pathway, and its deregulation is known to contribute toward tumorigenesis.^1,2 Mesenchymal tumors with GLI1 gene abnormalities are a rare classification of neoplasms whose clinicopathologic features and etiology are currently evolving.¹ There are several fusion products reported with GLI1 mesenchymal tumors, including ACTB, MALAT1, and PTCH1.¹ Specifically with regard to ACTB::GLI1 MENs, these neoplasms present within soft tissues of the head/neck, limbs, and trunk, with one case identified in the skin.¹ On histopathology, ACTB::GLI1 MENs are composed of round to epithelioid cells arranged in nests or cords, resembling glomus tumor, glomangiopericytoma, myopericytoma, or myoepithelioma.¹ By immunohistochemistry, the tumor cells are usually positive for S100 protein and CD56 and negative for SOX10 and SMA.^1,2 As metastatic disease to the lungs and lymph nodes has been reported, complete excision with negative margins and close continued clinical follow-up are recommended.^1,2