<i>NTRK1</i>-rearranged histiocytosis: clinicopathologic and molecular features

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 partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46), and ARHGEF2 (1/46). Clinical outcomes were favorable, including spontaneous disease regression in 3 of 4 newborns with systemic disease, and rapid clinical response in both patients with a brain or bronchial tumor treated with the TRK inhibitor larotrectinib. This study advances the molecular characterization of histiocytoses and may guide the diagnosis and personalized treatment of patients.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2025-05-02
DOI
https://doi.org/10.1182/bloodadvances.2025016167
Citations
3
Primary Topic
Histiocytic Disorders and Treatments
Type
article
Field-Weighted Citation Impact
3.49

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

NTRK1-rearranged histiocytosis: clinicopathologic and molecular features

Jonhan Ho, Astrid G. S. van Halteren, Arivarasan Karunamurthy, Lenka Krsková et al.
3 citations
Blood Advances
Histiocytic Disorders and Treatments
3.49
article

NTRK1-rearranged histiocytosis: clinicopathologic and molecular features

Jonhan Ho, Astrid G. S. van Halteren, Arivarasan Karunamurthy, Lenka Krsková, Jan van Laar, Jean Donadieu, Martin Jankofsky, Arndt Borkhardt, Philippe Drabent, B. Bonsang, Benjamin H. Durham, Robert M. Verdijk, Zofia Hélias‐Rodzewicz, Somak Roy, Eric D. Carlsen, Jozef Zlocha, Florian Babor, Roos J. Leguit, Robert B. Lorsbach, Jennifer Picarsic, Sébastien Heritier, Jean‐François Emile, Marie‐Laure Jullié, Paul G. Kemps, Eli L. Diamond, Karel Švojgr, Allison L. Bartlett, Ashish Kumar, Sylvie Fraïtag, Julien Haroche, Mariarita Santi, Subhra Dhar, Arunaloke Bhattacharya, Andrica C. H. de Vries, Rivers Fragneau
article en
3 citations

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 partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46), and ARHGEF2 (1/46). Clinical outcomes were favorable, including spontaneous disease regression in 3 of 4 newborns with systemic disease, and rapid clinical response in both patients with a brain or bronchial tumor treated with the TRK inhibitor larotrectinib. This study advances the molecular characterization of histiocytoses and may guide the diagnosis and personalized treatment of patients.

Blood AdvancesVol. 9(14)
Rutgers, The State University of New Jersey (US), Cincinnati Children's Hospital Medical Center (US), Hôpital Necker-Enfants Malades (FR), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Philadelphia (US), Université de Bordeaux (FR), Inserm (FR), Universität Hamburg (DE), University of Pittsburgh (US), Utrecht University (NL), Charles University (CZ), Université Paris-Saclay (FR), Leiden University Medical Center (NL), Erasmus MC (NL), Centre Hospitalier Universitaire de Bordeaux (FR), University Medical Center Utrecht (NL), Sorbonne Université (FR), Hôpital Armand-Trousseau (FR), Assistance Publique – Hôpitaux de Paris (FR), University Hospital in Motol (CZ), UPMC Health System (US), Bordeaux Population Health (FR), University Medical Center Hamburg-Eppendorf (DE), Duke Medical Center (US), Children's Hospital of Pittsburgh (US), College of Medicine & JNM Hospital (IN), Hôpital Ambroise-Paré (FR), Centre de Recherche Saint-Antoine (FR), University of Pittsburgh Medical Center (US), Institute of Child Health (IN), Erasmus MC - Sophia Children’s Hospital (NL), Klinikum Chemnitz (DE), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (FR), Heinrich Heine University Düsseldorf (DE), Erasmus University Rotterdam (NL)
Cincinnati Children's Hospital Medical Center, Association Pour la Recherche et L'enseignement en Pathologie
Partnerships for the goals
Openalex Percentile: Top 8%
Histiocytic Disorders and Treatments
3.49
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.