{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:06:37Z","timestamp":1792688797453,"version":"4.5.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>NTRK-rearranged spindle cell neoplasm occurs predominantly in the superficial or deep soft tissues of extremities or trunk. Occurrence in the visceral organs is extremely rare. Herein, we describe 8 cases of NTRK-rearranged spindle cell neoplasm that arose primarily in the gastrointestinal tract. Patients included 5 males and 3 females with age at presentation ranging from 6 to 63 years (median: 29.5 years). Tumors occurred in the colon (n=3), small intestine (n=2), rectum (n=2), and stomach (n=1). Tumor size ranged from 3.5 to 9\u00a0cm (median: 5\u00a0cm). Morphologically, 4 tumors were low-grade, composed of haphazard or intertwining fascicles of spindle cells, with prominent interstitial collagen fibers and ring-like perivascular hyalinization being present in 2 tumors. The other 4 tumors were histologically high-grade sarcomas, consisting of sweeping fascicles of atypical spindle cells showing increased cellularity and brisk mitotic activity. Immunohistochemically, 6\/6 cases (100%) showed diffuse and strong cytoplasmic staining of pan-TRK. Variable expression of TrkA, CD34, and S100 was noted in 5\/5 (100%), 5\/8 (62.5%), and 4\/7 (57.1%) cases, respectively. Fluorescence in situ hybridization analysis showed <jats:italic toggle=\"yes\">NTRK1<\/jats:italic> rearrangement (n=7) and <jats:italic toggle=\"yes\">NTRK2<\/jats:italic> rearrangement (n=1). In cases with available materials, RNA sequencing identified <jats:italic toggle=\"yes\">LMNA::NTRK1<\/jats:italic> (n=3), <jats:italic toggle=\"yes\">TPM3::NTRK1<\/jats:italic> (n=2), and <jats:italic toggle=\"yes\">STRN::NTRK2<\/jats:italic> (n=1) fusions. At follow-up (range: 4 to 30 months; median: 12.5 months), 6 of 7 patients who underwent surgery had no evidence of disease at last follow-up. One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery. One patient was treated with larotrectinib alone. He showed significant response at 7 months after treatment. NTRK-rearranged spindle cell neoplasm represents an exceptionally rare entity in the gastrointestinal tract. The presence of interstitial collagen fibers and ring-like perivascular hyalinization and co-expression of CD34 and S100 are diagnostic clues to low-grade neoplasms. However, high-grade sarcomas pose a considerable diagnostic challenge to pathologists owing to the lack of specific features. The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.<\/jats:p>","DOI":"10.1097\/pas.0000000000002202","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T11:00:45Z","timestamp":1711364445000},"page":"623-631","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases"],"prefix":"10.1097","volume":"48","author":[{"given":"Xiaojiao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pathology, Fudan University Shanghai Cancer Center"},{"name":"Department of Pathology, The First People\u2019s Hospital of Kunshan, Kunshan, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Kunshan, Kunshan, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fudan University Shanghai Cancer Center"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Weng","family":"Lao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fudan University Shanghai Cancer Center"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fudan University Shanghai Cancer Center"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fudan University Shanghai Cancer Center"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"R1-20250608","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1097\/PAS.0000000000000675","article-title":"Recurrent NTRK1 gene fusions define a novel subset of locally aggressive lipofibromatosis-like neural tumors","volume":"40","author":"Agaram","year":"2016","journal-title":"Am J Surg Pathol"},{"key":"R2-20250608","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/PAS.0000000000001203","article-title":"Expanding the spectrum of pediatric NTRK-rearranged mesenchymal tumors","volume":"43","author":"Davis","year":"2019","journal-title":"Am J Surg Pathol"},{"key":"R3-20250608","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1097\/PAS.0000000000001055","article-title":"NTRK fusions define a novel uterine sarcoma subtype with features of fibrosarcoma","volume":"42","author":"Chiang","year":"2018","journal-title":"Am J Surg Pathol"},{"key":"R4-20250608","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/gcc.22767","article-title":"The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements","volume":"58","author":"Suurmeijer","year":"2019","journal-title":"Genes Chromosomes Cancer"},{"key":"R5-20250608","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/PAS.0000000000001929","article-title":"NTRK-rearranged uterine sarcomas: clinicopathologic features of 15 cases, literature review, and risk stratification","volume":"46","author":"Costigan","year":"2022","journal-title":"Am J Surg Pathol"},{"key":"R6-20250608","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/his.14069","article-title":"NTRK fusion cervical sarcoma: a report of three cases, emphasising morphological and immunohistochemical distinction from other uterine sarcomas, including adenosarcoma","volume":"77","author":"Rabban","year":"2020","journal-title":"Histopathology"},{"key":"R7-20250608","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1097\/PAS.0000000000001880","article-title":"Primary NTRK-rearranged spindle cell neoplasm of the lung: a clinicopathologic and molecular analysis of 3 cases","volume":"46","author":"Zhu","year":"2022","journal-title":"Am J Surg Pathol"},{"key":"R8-20250608","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41379-021-01005-3","article-title":"Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements","volume":"35","author":"Tsai","year":"2022","journal-title":"Mod Pathol"},{"key":"R9-20250608","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41379-020-0623-z","article-title":"Mesenchymal tumors of the gastrointestinal tract with NTRK rearrangements: a clinicopathological, immunophenotypic, and molecular study of eight cases, emphasizing their distinction from gastrointestinal stromal tumor (GIST)","volume":"34","author":"Atiq","year":"2021","journal-title":"Mod Pathol"},{"key":"R10-20250608","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/gcc.23132","article-title":"Primary NTRK-rearranged spindle cell neoplasm of bone harboring an HMBOX1::NTRK3 gene fusion","volume":"62","author":"Wang","year":"2023","journal-title":"Genes Chromosomes Cancer"},{"key":"R11-20250608","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/ajcp\/aqab167","article-title":"Expanding the spectrum of adult NTRK3-rearranged spindle cell neoplasms: a recurrent NTRK3-SQSTM1 fusion spindle cell tumor with deceptively bland morphology","volume":"157","author":"Punjabi","year":"2022","journal-title":"Am J Clin Pathol"},{"key":"R12-20250608","doi-asserted-by":"crossref","first-page":"740676","DOI":"10.3389\/fonc.2021.740676","article-title":"Case report: adult NTRK-rearranged spindle cell neoplasm: early tumor shrinkage in a case with bone and visceral metastases treated with targeted therapy","volume":"11","author":"Recine","year":"2022","journal-title":"Front Oncol"},{"key":"R13-20250608","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/gcc.22671","article-title":"A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1\/2 genes","volume":"57","author":"Suurmeijer","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"R14-20250608","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1053\/j.gastro.2020.06.052","article-title":"Unusual colonic polyp in a young woman","volume":"160","author":"Bertolini","year":"2021","journal-title":"Gastroenterology"},{"key":"R15-20250608","first-page":"76","article-title":"Intestinal infantile fibrosarcoma with translocation of NTRK. A case report and review of the literature","volume":"56","author":"Soler","year":"2023","journal-title":"Rev Esp Patol"},{"key":"R16-20250608","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3233\/CBM-220357","article-title":"Pan-TRK immunohistochemistry as screening tool for NTRK fusions: a diagnostic workflow for the identification of positive patients in clinical practice","volume":"38","author":"Vingiani","year":"2023","journal-title":"Cancer Biomark"},{"key":"R17-20250608","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41379-019-0324-7","article-title":"NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls","volume":"33","author":"Solomon","year":"2020","journal-title":"Mod Pathol"},{"key":"R18-20250608","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41379-020-0495-2","article-title":"NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations","volume":"33","author":"Kao","year":"2020","journal-title":"Mod Pathol"},{"key":"R19-20250608","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/his.14884","article-title":"A systematic comparison of pan-Trk immunohistochemistry assays among multiple cancer types","volume":"82","author":"Haberecker","year":"2023","journal-title":"Histopathology"},{"key":"R20-20250608","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1097\/PAI.0000000000000933","article-title":"Fluorescent in situ hybridization must be preferred to pan-TRK immunohistochemistry to diagnose NTRK3-rearranged gastrointestinal stromal tumors (GIST)","volume":"29","author":"Castillon","year":"2021","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"R21-20250608","article-title":"Durable clinical response to larotrectinib in an adolescent patient with an undifferentiated sarcoma harboring an STRN-NTRK2 Fusion","volume":"2","author":"Wu","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"R22-20250608","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13000-023-01400-1","article-title":"Identification of dual STRN-NTRK2 rearrangements in a high grade sarcoma, with good clinical response to first-line larotrectinib therapy","volume":"18","author":"Lin","year":"2023","journal-title":"Diagn Pathol"},{"key":"R23-20250608","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1200\/PO.19.00287","article-title":"Response and mechanisms of resistance to larotrectinib and selitrectinib in metastatic undifferentiated sarcoma harboring oncogenic fusion of NTRK1","volume":"4","author":"Hemming","year":"2020","journal-title":"JCO Precis Oncol"},{"issue":"uppl 1","key":"R24-20250608","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1097\/01.PAT.0000461658.78598.52","article-title":"Solitary fibrous tumour of transverse mesocolon: an unusual location","volume":"47","author":"Scarlett","year":"2015","journal-title":"Pathology"},{"key":"R25-20250608","doi-asserted-by":"crossref","first-page":"rjac097","DOI":"10.1093\/jscr\/rjac097","article-title":"Case report of mesenteric solitary fibrous tumour and review of the literature: \u2018once in a blue moon","volume":"2022","author":"Nicotera","year":"2022","journal-title":"J Surg Case Rep"},{"key":"R26-20250608","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/his.14010","article-title":"Diagnostic utility of pan-Trk immunohistochemistry for inflammatory myofibroblastic tumours","volume":"76","author":"Yamamoto","year":"2020","journal-title":"Histopathology"},{"key":"R27-20250608","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jmoldx.2019.03.008","article-title":"Detection of tumor NTRK gene fusions to identify patients who may benefit from tyrosine kinase (TRK) inhibitor therapy","volume":"21","author":"Hsiao","year":"2019","journal-title":"J Mol Diagn"}],"container-title":["American Journal of Surgical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000002202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T20:05:49Z","timestamp":1749413149000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000002202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/pas.0000000000002202","relation":{},"ISSN":["0147-5185"],"issn-type":[{"value":"0147-5185","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3,25]]}}}