Progressive Metastatic Cutaneous TFCP2::FUS Fusion-Positive Rhabdomyosarcoma: A Case Report

Rhabdomyosarcoma (RMS) rarely exhibits the TFCP2::FUS gene fusion and is even more rarely present as multiple cutaneous lesions.

We describe the case of a 48-year-old man who presented with multiple cutaneous masses eroding through the skin as well as visceral metastases following two previous resections for cutaneous neoplasms. Histopathology showed spindle morphology and positive staining for keratins, desmin, MYOD1, and myogenin. Genetic sequencing showed a noncanonical TFCP2::FUS fusion that, in combination with the immunohistochemistry, was diagnostic of RMS. He was treated with vincristine, dactinomycin, and cyclophosphamide, followed by cabozantinib and pembrolizumab, and finally pembrolizumab and concurrent radiation therapy to the targetable lesions. He had a continual, rapid progression of disease and expired 2 months following radiation.

This case is notable because it presents a rare example of an aggressive, TFCP2::FUS gene fusion-positive RMS presenting with multiple cutaneous metastases, and highlights that this entity is highly resistant to multiple chemotherapies, immunotherapy, and radiation therapy.