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Primary NTRK-rearranged Spindle Cell Neoplasm of the Lung

Three cases of primary NTRK-rearranged spindle cell neoplasm of the lung with resemblance to those described in the somatic soft tissues are presented. The patients are 2 males and 1 female with age at presentation ranging from 31 to 45 years (mean, 36 y). All the 3 tumors were discovered incidentally during physical examinations. None of the patients had any prior history of mesenchymal neoplasms anywhere else. Computed tomography revealed intrapulmonary mass located in the right upper lobe, left upper lobe, and left lower lobe, respectively. All the patients underwent lobectomy. Grossly, the tumors were described as yellowish-white solid measuring in size between 1.2 and 1.8 cm (mean, 1.5 cm). Histologically, they were characterized by monomorphic spindle cells arranged in haphazard fascicles accompanied by variable stromal collagens. Nuclear atypia was mild and mitotic activity was scarce. By immunohistochemistry, the neoplastic cells in all 3 cases showed strong and diffuse staining of CD34, pan-TRK, and TrkA with variable expression of S100 protein, whereas they were negative for cytokeratin, SOX10, ALK, α-smooth muscle actin, desmin, and STAT6. Fluorescence in situ hybridization analysis revealed NTRK1 rearrangement in all 3 cases. Subsequent next-generation sequencing identified TPM3-NTRK1 fusion in 2 cases and LMNA-NTRK1 fusion in 1 case. All 3 patients are alive without the disease (median follow-up, 9 mo; range, 4 to 87 mo). The cases present herein demonstrate that NTRK-rearranged spindle cell neoplasms may occur primarily in the lung, albeit extremely rare, and should be included in the differential diagnosis of primary pulmonary spindle cell neoplasms.