LDB1::KMT2A Fusion in a Spindle‐Cell Sarcoma: A Case Report

ABSTRACT KMT2A ‐rearranged sarcomas represent a heterogeneous group of tumors with clinical behaviors ranging from surgical cure to local recurrence and metastasis. Previously reported fusion partners include YAP1 and VIM : YAP1::KMT2A::YAP1 is associated with sclerosing epithelioid fibrosarcoma (SEF)‐like histology, whereas VIM::KMT2A tumors exhibit a small round‐to‐spindle cell morphology. A third fusion, CBX6::KMT2A::PYGO1 , was reported with a spindle‐cell morphology somewhat different from the YAP1::KMT2A::YAP1 pattern. Here, we describe a novel LDB1::KMT2A fusion in a spindle‐cell sarcoma. The case involves a 19‐year‐old male who presented with an 8 cm mass situated in the left erector spinae muscle. Histopathological examination revealed a biphasic pattern comprising hypercellular fascicular/matted regions and hypocellular fibroma‐like areas. Immunohistochemistry revealed diffuse positivity for CD99, SATB2, cyclin D1, BCL2, TLE1, pan‐TRK, and NKX2.2, with focal BCOR expression and a Ki‐67 proliferation index of approximately 10%. The tumor was negative for MUC4, SS18‐SSX, WT1, cytokeratin (CKpan), vimentin, CD34, S‐100, SOX10, SMA, STAT6, desmin, and MyoD1. Comprehensive genomic profiling via next‐generation sequencing (NGS) identified a novel LDB1::KMT2A fusion, involving exons 1–10 of LDB1 and exons 4–36 of KMT2A . The rearrangement was verified using fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT‐PCR) techniques. Additionally, a pathogenic BCOR frameshift mutation (c.3203dup, p.E1069Gfs*10) was identified. The patient underwent wide surgical excision and remains disease‐free at a 5‐month follow‐up. This report presents the first known case of an LDB1::KMT2A fusion in a spindle‐cell sarcoma, expanding the molecular spectrum of the emerging entity of KMT2A ‐rearranged sarcomas.