NTRK-rearranged uterine sarcoma is a recently described entity that represents a subset of uterine sarcomas with distinct clinicopathological features. From a molecular point of view, this tumour is defined by NTRK gene rearrangement, resulting in overexpression or constitutive activation of Trk receptors. The presence of NTRK fusion is indicative of treatment response with a selective small-molecule inhibitor of the Trk kinases. Here, we report a case of an NTRK-rearranged sarcoma of the uterine cervix in a 43-year-old patient, measuring 80 mm in its largest dimension, with a novel NUMA1-NTRK1 fusion, not previously reported in NTRK-rearranged uterine sarcomas or other NTRK-rearranged tumours. The fusion, involving NUMA1 exon 14 (NM_006185.4) and NTRK1 exon 11 (NM_002529.4), was identified by next-generation sequencing (NGS) studies (FusionPlex Pan Solid Tumor v2 panel). Although the presence of NTRK fusion has been reported in a variety of neoplasms, a fusion involving NUMA1 (nuclear mitotic apparatus protein 1) and a tyrosine kinase partner has previously been reported in human neoplasms only in a handful of cases. The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.

NTRK重排子宫肉瘤是最近描述的一种实体，代表具有独特临床病理学特征的子宫肉瘤的子集。从分子角度来看，这种肿瘤的定义是NTRK基因重排，导致Trk受体过度表达或组成型激活。 NTRK融合的存在表明 Trk 激酶选择性小分子抑制剂的治疗反应。在这里，我们报道了一名 43 岁患者的NTRK重排宫颈肉瘤病例，最大尺寸为 80 毫米，具有新颖的NUMA1 - NTRK1融合，这是以前在NTRK重排子宫肉瘤中未报道的或其他NTRK重排肿瘤。通过下一代测序 (NGS) 研究（FusionPlex Pan Solid Tumor v2 panel）鉴定了涉及NUMA1外显子 14 (NM_006185.4) 和NTRK1外显子 11 (NM_002529.4) 的融合。尽管在多种肿瘤中存在NTRK融合的报道，但之前仅在少数病例中报道了人类肿瘤中涉及NUMA1 （核有丝分裂装置蛋白 1）和酪氨酸激酶伴侣的融合。由此产生的融合蛋白包含 NUMA1 的寡聚化结构域，预计该结构域会导致 NTRK1 酪氨酸激酶结构域的持续激活。由于潜在的靶向治疗方案的可用性，对这些肿瘤的识别和准确诊断非常重要。