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

Area of Science:

• Oncology
• Molecular Pathology
• Genetics

Background:

• KMT2A-rearranged sarcomas are a diverse group of tumors with varied clinical outcomes.
• Previous studies identified YAP1::KMT2A and VIM::KMT2A fusions associated with distinct histological subtypes.
• A third fusion, CBX6::KMT2A::PYGO1, was also reported with a specific spindle-cell morphology.

Purpose of the Study:

• To report a novel LDB1::KMT2A gene fusion in a spindle-cell sarcoma.
• To characterize the histopathological and molecular features of this newly identified sarcoma subtype.
• To contribute to the expanding understanding of KMT2A-rearranged sarcomas.

Main Methods:

• Histopathological examination and immunohistochemistry of an 8cm left erector spinae muscle mass.
• Comprehensive genomic profiling using next-generation sequencing (NGS) to identify gene fusions.
• Fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT-PCR) for rearrangement verification.

Main Results:

• Identification of a novel LDB1::KMT2A fusion in a 19-year-old male with spindle-cell sarcoma.
• Histopathology revealed a biphasic pattern with specific immunohistochemical markers (CD99, SATB2, cyclin D1, BCL2, TLE1, pan-TRK, NKX2.2).
• A pathogenic BCOR frameshift mutation was also detected; the patient remains disease-free post-surgery.

Conclusions:

• This is the first reported case of an LDB1::KMT2A fusion in spindle-cell sarcoma.
• The findings expand the molecular spectrum of KMT2A-rearranged sarcomas.
• This discovery enhances the classification and potential targeted therapies for these rare tumors.