Primary NTRK-rearranged Spindle Cell Neoplasm of the Lung

Abstract

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.

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

“…The combined usage of pan-TRK and TrkA may help identify low-grade neoplasms with NTRK1 rearrangement. 7 Of 17 cases, 10 co-expressed CD34 and S100 (10/17, 58.8%), including 5 low-grade, 1 intermediategrade and 4 high-grade tumors. Generally, CD34 and S100 were diffusely expressed in low-grade tumors, whereas they were often focally expressed in high-grade tumors.…”

“…However, occurrence in the visceral organs has also been described, albeit very rare. Reported sites include uterus (especially uterine cervix), 5,6 intrathoracic cavity (lung, pleura, and heart), 7,8 gastrointestinal (GI) tract, 9 prostate, 8 and bone 10 . In addition, its manifestation in adulthood has also been well documented 8, …”

Primary NTRK‐rearranged spindle cell neoplasm of bone harboring an HMBOX1::NTRK3 gene fusion

“…The majority of mesenchymal tumors with NTRK rearrangement occur in the superficial and deep soft tissues of the extremities, trunk, or head and neck. Occasionally, the tumor may also arise in visceral organs, including the gastrointestinal tract, uterine cervix, the central nervous system, and rarely lung 3–7 . The occurrence of NTRK ‐rearranged spindle cell tumor as a primary lesion in the bone is extremely rare.…”

“…Occasionally, the tumor may also arise in visceral organs, including the gastrointestinal tract, uterine cervix, the central nervous system, and rarely lung. [3][4][5][6][7] The occurrence of NTRKrearranged spindle cell tumor as a primary lesion in the bone is extremely rare. According to a recent study that embraced 354 bone tumors, NTRK fusions were not identified.…”

“…The majority arise in the superficial or deep soft tissues of the extremities, trunk, head, and neck. Occasionally, it may occur in the visceral organs, including gastrointestinal tract, 3 uterine cervix, 4,5 central nervous system, 6 and lung 7 . However, occurrence as a primary bony neoplasm, to the best of our knowledge, has not been described thus far 8 .…”