NTRK1-rearranged histiocytosis: Clinicopathologic and molecular features Journal Article
| Authors: | Fragneau, R.; Fraitag, S.; Kemps, P. G.; Hélias-Rodzewicz, Z.; Roy, S.; Bonsang, B.; Bartlett, A. L.; Dhar, S.; Jankofsky, M.; Zlocha, J.; Svojgr, K.; Krsková, L.; de Vries, A. C. H.; Verdijk, R. M.; van Laar, J. A. M.; Leguit, R. J.; Drabent, P.; Carlsen, E. D.; Ho, J.; Karunamurthy, A. D.; Santi, M.; Jullié, M. L.; Babor, F.; Lorsbach, R.; van Halteren, A. G. S.; Héritier, S.; Diamond, E. L.; Durham, B. H.; Kumar, A. R.; Bhattacharya, A.; Haroche, J.; Donadieu, J.; Borkhardt, A.; Picarsic, J. L.; Emile, J. F. |
| Article Title: | NTRK1-rearranged histiocytosis: Clinicopathologic and molecular features |
| Abstract: | Non-Langerhans cell histiocytoses are a diverse group of histiocytic diseases. Different entities are defined based on clinical, histopathologic, and/or molecular characteristics. This study aimed to define NTRK-rearranged histiocytosis. Through international collaboration, we investigated 50 cases of histiocytosis with pan-tropomyosin receptor kinase (pan-TRK) expression and/or in-frame NTRK rearrangement. We also analyzed 45 control xanthogranulomas using pan-TRK immunohistochemistry and targeted RNA sequencing. Slides were centrally reviewed; clinical and molecular data were collected. The 50 cases comprised 30 children and 20 adults with a median age of 11.5 years (range, 0-73 years) and a male predominance (64%). Most patients (88%) had disease limited to the skin, including a single skin nodule in 41 patients and multiple skin lesions in 3 others. Four newborns presented with skin lesions, hepatomegaly, and thrombocytopenia that required transfusions. The 2 remaining patients had life-threatening lesions of the brain or bronchus. All cases displayed xanthogranuloma histology, often including foamy histiocytes and Touton giant cells. Histiocytes stained positive for pan-TRK in 50 of 50 cases, whereas all 45 control xanthogranulomas without in-frame NTRK fusions stained negative. NTRK1 fusion © 2025 American Society of Hematology. Published by Elsevier Inc. |
| Keywords: | • ntrk1-rearranged histiocytosis often presents as 1 or multiple cutaneous xanthogranulomas but may rarely involve extracutaneous tissues; • targeted therapy with the trk inhibitor larotrectinib is highly effective in patients with severe extracutaneous disease |
| Journal Title: | Blood Advances |
| Volume: | 9 |
| Issue: | 14 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-07-22 |
| Start Page: | 3617 |
| End Page: | 3628 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2025016167 |
| PUBMED: | 40315374 |
| PROVIDER: | scopus |
| PMCID: | PMC12281165 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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