Abstract

A 44-year-old female with no prior personal or family history of malignancy was referred to our tertiary cancer center for surgical and medical oncologic treatment of a thigh lesion. The patient first presented to her local dermatologist with an asymptomatic new pink 1.2cm subcutaneous nodule on the right posterior thigh and underwent elective excision for a presumed cyst. Excision and pathology at the outside institution revealed an unencapsulated dermal nodular proliferation of epithelioid and spindled cells surrounding dilated vessels within a possible lymph node. Immunohistochemical staining revealed positivity for Melan-A and negativity for S-100, panCK, HMWK, and CD31, and the lesion was diagnosed as metastatic melanoma. Staging PET/CT failed to reveal other foci of metastatic disease. Upon referral to our institution, review and additional immunohistochemistry revealed tumor positivity for vimentin, actin, and caldesmon with repeat Melan-A staining negative, weak HMB45 staining, and a 5-10% Ki-67 proliferative index with differential diagnoses including a myopericytic tumor and perivascular epithelioid cell tumor. Primary next generation sequencing and additional extended fusion panel molecular analyses revealed three PDGFRB gene copies and a CARMN::NOTCH2 in-frame fusion, respectively. Unifying the molecular and immunohistochemical profile of the tumor, a diagnosis of malignant glomus tumor was achieved. The patient underwent complete excision of the tumor with no evidence of residual disease. This case highlights the importance of molecular profiling for dermal epithelioid/spindle cell tumors of uncertain origin or felt to be metastases, especially in absence of prior known malignancy.