Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy Journal Article
| Authors: | Friedman, J. S.; Durham, B. H.; Reiner, A. S.; Yabe, M.; Petrova-Drus, K.; Dogan, A.; Pulitzer, M.; Busam, K. J.; Francis, J. H.; Rampal, R. K.; Ulaner, G. A.; Reddy, R.; Yeh, R.; Hatzoglou, V.; Lacouture, M. E.; Rotemberg, V.; Mazor, R. D.; Hershkovitz-Rokah, O.; Shpilberg, O.; Goyal, G.; Go, R. S.; Abeykoon, J. P.; Rech, K.; Morlote, D.; Fidai, S.; Gannamani, V.; Zia, M.; Abdel-Wahab, O.; Panageas, K. S.; Rosenblum, M. K.; Diamond, E. L. |
| Article Title: | Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy |
| Abstract: | Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai–Dorfman–Destombes disease (RDD) and Erdheim–Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19–137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03–0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy. © 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. |
| Keywords: | immunohistochemistry; signal transduction; adolescent; adult; child; clinical article; human tissue; preschool child; aged; child, preschool; middle aged; young adult; gene mutation; overall survival; somatic mutation; genetics; mutation; clinical trial; histopathology; nuclear magnetic resonance imaging; phenotype; computer assisted tomography; skin biopsy; protein kinase inhibitor; prevalence; cell differentiation; pathology; immunoreactivity; retrospective study; histology; hematuria; protein kinase inhibitors; cd20 antigen; multicenter study; gene fusion; mitogen activated protein kinase 3; targeted therapy; histiocyte; drug therapy; immunosuppressive treatment; mediastinoscopy; b raf kinase; proto-oncogene proteins b-raf; braf protein, human; histiocytes; langerhans cell histiocytosis; molecularly targeted therapy; genotyping; bone marrow tumor; molecular targeted therapy; acute myeloid leukemia; histiocytoma; histiocytosis, langerhans-cell; mapk signaling; sanger sequencing; humans; human; male; female; article; sinus histiocytosis; erdheim chester disease; histiocytosis, sinus; erdheim-chester disease; whole exome sequencing; myeloid neoplasm; mapk signalling |
| Journal Title: | British Journal of Haematology |
| Volume: | 205 |
| Issue: | 1 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2024-07-01 |
| Start Page: | 127 |
| End Page: | 137 |
| Language: | English |
| DOI: | 10.1111/bjh.19462 |
| PUBMED: | 38613141 |
| PROVIDER: | scopus |
| PMCID: | PMC11245369 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Eli L. Diamond -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work