Expanding the Spectrum of Adult NTRK3-Rearranged Spindle Cell Neoplasms: A Recurrent NTRK3-SQSTM1 Fusion Spindle Cell Tumor With Deceptively Bland Morphology

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.

When is a lipoma not a lipoma? Case report presenting a lipoblastoma-like tumor of the gluteal cleft in an older gentleman with literature review

“…Given the findings on imaging, the differential is broad but from a clinical, pathologic, and molecular standpoint, LLTs have similarities to low-grade myxofibrosarcoma (similar morphological appearance, but intact Rb expression and lack of SMA expression argues against this) [15] , cellular angiofibroma (similar morphological appearance, both desmin − CD34 + , but intact Rb and S100 expression argues against this) [14] , [16] , atypical spindle cell lipomatous tumor (both are negative for MDM2 amplification, CD34 + S100 + , but Rb is typically lost in this tumor) [7] , myxoid liposarcoma (both negative for MDM2 amplification and S100 + , although the absence of DDIT3 translocation argues against this) [3] , [9] , [17] , and spindle cell tumors (both SOX10 − CD34 + S100 + , but lacking NTRK expression/gene fusion commonly found in spindle cell tumors makes it unlikely) [18] .…”

A morphological mimic: An NTRK3‐rearranged spindle cell neoplasm presenting as a groin mass

“…NTRK-rearranged spindle cell neoplasms are a recently described group of soft tissue tumors that are morphologically separate from infantile fibrosarcoma. [1][2][3] Most have gene fusions involving NTRK1 and they commonly present in children and young adults as a painless mass on the extremities or trunk. NTRK2 and NTRK3 rearrangements occur less frequently.…”

Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases

“…10 In addition, its manifestation in adulthood has also been well documented. 8,11,12 Largely due to the morphological heterogeneity and nonconsistent immunophenotype, NTRK-rearranged spindle cell neoplasm poses a considerable diagnostic challenge to pathologists, especially with regard to those occurring at unusual sites. As to the GI tract, very few cases of NTRK-rearranged mesenchymal neoplasm have been reported to date, with the literature limited to isolated cases or few cases included in small series.…”