The Histologic Spectrum of Soft Tissue Spindle Cell Tumors with NTRK3 Gene Rearrangements

Albert J Suurmeijer, Brendan C Dickson, David Swanson, Lei Zhang, Yun-Shao Sung, Hsuan-Ying Huang, Christopher D Fletcher, Cristina R Antonescu
Genes, Chromosomes & Cancer 2019 May 21
NTRK3-rearranged tumors other than infantile fibrosarcomas harboring the canonical ETV6-NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of 7 tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1-67 years). Tumors were located in extremities, trunk, retroperitoneum, or intraabdominal. In all tumors FISH revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan-TRK by IHC. Two cases showed low to intermediate grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands and perivascular rings of hyalinized collagen and co-expression of S100 and CD34. The remaining 5 cases were high-grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either MPNSTs or fibrosarcomas. Two high-grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high-grade NTRK3-rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan-TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK-rearranged neoplasms. This article is protected by copyright. All rights reserved.


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