Expanding the Spectrum of Adult NTRK3-Rearranged Spindle Cell Neoplasms

Abstract

Abstract Objectives NTRK-rearranged spindle cell neoplasms (other than infantile fibrosarcoma) are an emerging entity of tumors that demonstrate wide variation in clinical and histopathologic features. We report a case of an NTRK-rearranged spindle cell neoplasm bearing a deceptively bland morphology. Methods We performed histopathologic, immunohistochemical, and molecular evaluation on resection tissue. We also conducted a literature review on adult NTRK3-rearranged spindle cell neoplasms. Results The tumor presented as a recurrent ankle mass in an elderly patient. Histologically, it was composed of bland spindle cells set in a fibrous to edematous stroma. Blood vessels were interspersed with subtle perivascular hyalinization and scattered lymphoid aggregates. Immunohistochemically, the spindle cells expressed CD34 and S100 while being negative for SOX10. The tumor also showed cytoplasmic reactivity for pan–tyrosine receptor kinase immunohistochemistry. Next-generation sequencing identified an NTRK3-SQSTM1 fusion. To the best of our knowledge, this fusion pair has not been previously reported in adult NTRK-rearranged mesenchymal tumors. Conclusions Altogether, this rare and diagnostically challenging case of an NTRK3-rearranged spindle cell tumor with low-grade morphology is in contrast to many of the reported adult NTRK3-rearranged mesenchymal tumors. Recognition of low-grade NTRK-rearranged tumors demands close attention to clues in morphology and immunoprofiles.