The majority of neurotrophic tyrosine receptor kinase (NTRK) rearranged neoplasms occur either in the superficial or deep soft tissues of extremities or trunk. Occasionally, it arises in visceral organs. However, its occurrence as a primary osseous tumor has not been documented thus far. Herein, we describe a unique case of an NTRK rearranged neoplasm that presented as a primary bony lesion. The tumor occurred in a 21-year-old woman who presented with an increasing pain in the right lower extremity. Radiologic examinations revealed a destructive lytic lesion located in the lower portion of the right femur. Histologically, the tumor was composed of haphazard fascicles of monomorphic spindle cells displaying mild nuclear atypia and rare mitotic activity. Immunohistochemically, the tumor cells showed focal staining of pan-TRK and S100 protein. Fluorescence in situ hybridization analysis was performed with the utilization of break-apart probes for NTRK1/NTRK2/NTRK3 genes. An NTRK3 rearrangement was identified. Subsequent next-generation sequencing (RNA-seq) revealed HMBOX1exon6::NTRK3exon 14 fusion. Our study illustrates, albeit extremely rare, that NTRK-rearranged neoplasms can arise as a primary bone lesion. In addition, we describe a novel HMBOX1::NTRK3 fusion that has not been documented before.
Keywords: NTRK-rearranged neoplasm; NTRK3; bone; differential diagnosis.
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