ETV6::NTRK3 融合阳性野生型胃肠道间质瘤（GIST）伴大量淋巴浸润（TILs 和三级淋巴结构）：一例新病例报告及治疗意义与文献综述

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase ( c-kit ), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha ( PDGFRα ) mutations are considered wild-type (WT), and their diverse molecular alterations and biological behaviors remain uncertain.

They are usually not sensitive to tyrosine kinase inhibitors (TKIs). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase ( NTRK ) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST.

Herein, we report a new case of NTRK -fused WT high-risk GIST in a female patient with a large pelvic mass (large dimension of 20 cm). The tumor was removed, and the histopathology displayed spindle-predominant morphology with focal epithelioid areas, myxoid stromal tissue, and notable lymphoid infiltration with tertiary lymphoid structures. Ten mitoses were quantified in 50 high-power fields without nuclear pleomorphism.

DOG1 showed strong and diffuse positivity, and CD117 showed moderate positivity. Succinate dehydrogenase subunit B (SDHB) was retained, Pan-TRK was focal positive (nuclear pattern), and the proliferation index Ki-67 was 7%. Next-generation sequencing (NGS) detected an ETV6::NTRK3 fusion, and this finding was confirmed by fluorescence in situ hybridization (FISH), which showed NTRK3 rearrangement.

In addition, an RB1 mutation was found by NGS. The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered. After 3 months of follow-up, a new CT scan showed a complete response.

Based on our results and the cases from the literature, GISTs with NTRK fusions are very uncommon so far; hence, further screening studies, including more WT GIST cases, may increase the possibility of finding additional cases. The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions.

Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.