<i>NSD3::NUTM1</i> Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Prolonged Survival

Abstract

Nuclear Protein in Testis (NUT)-rearranged tumors comprise predominantly NUT carcinoma but also include certain lymphomas, leukemias, skin appendage tumors, and sarcomas. Although histologically diverse, all are genetically identified by oncogenic rearrangement in the NUTM1 gene. Many fusion partners occur, and NSD3 is NUT carcinoma’s third most common partner. Herein, we present a case of a 26-year-old man with an NSD3::NUTM1 fusion sarcoma. The patient presented at the age of 13 months with a scalp nodule. Over the next 24 years, he experienced five local recurrences and ultimately expired of a rapidly progressive recurrence. His treatment included surgical resections, radiation, and various chemotherapies. Deceptively, the clinical presentation and histopathology aligned with a malignant peripheral nerve sheath tumor, a diagnosis rendered at initial resection with concurrence by a national soft tissue tumor expert. The patient’s exceptionally long survival could be due to NSD3 as the fusion partner, aided by the initial small tumor size and young patient age. Thus, this case expands NUT fusion sarcomas’ histologic and immunohistochemical profile to include mimicking a malignant peripheral nerve sheath tumor (MPNST). Additionally, it indicates that the NSD3::NUTM1 fusion can drive sarcoma genesis.

Keywords

• malignant peripheral nerve sheath tumor
• <i>NSD3::NUTM1</i> fusion
• RNA sequencing
• neurofibroma
• NUT sarcoma