A Rare Case of a Malignant Epithelioid Neoplasm With an Underlying Novel EWSR1::ZBT44 Fusion, Identified on Next-Generation Sequencing (NGS)

Abstract

The clinicopathological spectrum of undifferentiated round cell sarcomas of bone and soft tissues is expanding after the 5th edition of the WHO classification. A 23-year-old male patient presented with a lump in his left thigh of 3 months’ duration. Radiological examination revealed a well-defined, solid-cystic lobulated, soft tissue lesion in the proximal medial region of his left thigh, measuring 7.7 cm in the largest dimension. The referring diagnosis was an epithelioid sarcoma. Histopathological review of the tumor sections revealed a cellular tumor composed of malignant epithelioid to focally “rhabdoid-like” cells in a variable hyalinized and myxoid stroma with geographic areas of necrosis. In addition, there were areas reminiscent of hemangiopericytomatous vasculature. By immunohistochemistry, the tumor cells were diffusely positive for CD34, focally and distinctly for pan keratin (AE1/AE3). INI1/SMARCB1 and SMARCA4 (BRG1) were diffusely positive (normal). Next-generation sequencing with a wide sarcoma panel revealed EWSR1exon8::ZBT44exon4 fusion. The present example constitutes the first malignant epithelioid tumor with a hemangiopericytomatous growth pattern, exhibiting this rare fusion. The differential diagnoses of this tumor and their corresponding immunohistochemical profile are discussed. This example highlights the value of NGS in unraveling rare fusions and in differentiating these tumors from their several mimics.