Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Genes Chromosomes Cancer. 2023 Aug;62(8):477-482. doi: 10.1002/gcc.23132. Epub 2023 Mar 7.
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.
大多数神经营养酪氨酸受体激酶（NTRK）重排肿瘤发生在四肢或躯干的浅表或深部软组织中。偶尔，它也会出现在内脏器官中。然而，迄今为止，尚未有文献记录其作为原发性骨肿瘤的发生。在此，我们描述了一个独特的 NTRK 重排肿瘤病例，该肿瘤表现为原发性骨病变。该肿瘤发生于一名 21 岁女性，她因右下肢疼痛加剧而就诊。影像学检查显示右股骨下段有一处破坏性溶骨性病变。组织学上，肿瘤由形态单一的梭形细胞杂乱成束组成，显示轻度核异型性和罕见有丝分裂活性。免疫组织化学染色显示肿瘤细胞泛 TRK 和 S100 蛋白局灶性染色。采用 NTRK1/NTRK2/NTRK3 基因断裂探针进行荧光原位杂交分析。鉴定出 NTRK3 重排。随后进行下一代测序（RNA-seq）显示 HMBOX1exon6::NTRK3exon 14 融合。我们的研究表明，尽管极为罕见，但 NTRK 重排肿瘤可以作为原发性骨病变出现。此外，我们还描述了一种以前未记录过的 HMBOX1::NTRK3 融合。
