ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 108 citations in OpenAlex.
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- Histiocytic sarcoma with a common clonal origin emerged after 33 years from B-cell precursor acute lymphoblastic leukemia.Journal of clinical and experimental hematopathology : JCEH · 2026Article
- Case Report: ALK-positive histiocytosis presenting as an adrenal mass: a diagnostic trap due to unusual morphology.Frontiers in oncology · 2026Article
- Durable Response in Histiocytic Sarcoma After Allogeneic Stem Cell Transplantation: A Case Report.Hematology reports · 2025Article
- Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors.Nature communications · 2025Article
- Genetically Modified Mouse Models for Sarcoma Research: A Comprehensive Review.Current oncology reports · 2025Review
- Establishment of human histiocytic sarcoma organoids dependent on the SHH/YAP pathway.Human cell · 2025Article
- Histiocytic Sarcoma: A Review and Update.International journal of molecular sciences · 2025Review
- An Unusual Case of Cutaneous Langerhans Cell Sarcoma Lacking S100 Expression: A Case Report and Review of the Literature.Journal of cutaneous pathology · 2025Review
- Recent advances in therapeutic strategies of Erdheim-Chester disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France.Blood advances · 2025Article
- Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy.Cancers · 2025Article
- Insights into etiology and management of a case of Langerhans cell histiocytosis manifesting as perianal lesions: a case report.Journal of medical case reports · 2025Article
- Synchronous clonally related anaplastic large cell lymphoma and malignant histiocytosis.Diagnostic pathology · 2025Article
- Construction of a glycosylation-related prognostic signature for predicting prognosis, tumor microenvironment, and immune response in soft tissue sarcoma.Frontiers in oncology · 2025Article
- Difficulties of Differentiating Primary Histiocytic Sarcoma of the Central Nervous System from Glioblastoma in Older Patients: Methylation Analysis and Review of the Literature.NMC case report journal · 2025Article
- BRAF V600E mutation and high expression of PD-L1 in Rosai-Dorfman disease: case report and review of the literature.Journal of hematopathology · 2024Review
- Primary CNS histiocytic sarcoma: Two case reports highlighting a novel MIGA2::BRAF gene fusion and genome-wide DNA methylation profiling results.Journal of neuropathology and experimental neurology · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have demonstrated recurrent activating mutations involving the classical MAPK and PI3K signaling pathways in a large proportion of histiocytic neoplasms, such as Langerhans cell histiocytosis. However, very little is known about the molecular genetics of histiocytic sarcoma, a rare aggressive malignant neoplasm that shows pathologic characteristics of mature macrophages. Here we report the genomic characteristics of a large cohort of histiocytic sarcomas (n = 28) using a targeted next-generation sequencing approach to identify driver alterations. We identified recurrent mutations involving the RAS-MAPK signaling pathway (MAP2K1, KRAS, NRAS, BRAF, PTPN11, NF1, CBL) in a majority (57%) of histiocytic sarcoma cases and report a clinical response to a MEK inhibitor (Cobimetinib) in a patient with a NF1-mutated histiocytic sarcoma. A smaller subset of cases (21%) also showed mutations resulting in activation of the PI3K signaling pathway (PTEN, MTOR, PIK3R1, PIK3CA). In addition, the tumor-suppressor gene CDKN2A was the most frequently altered gene (46%). Further, a subset of histiocytic sarcoma cases shows striking molecular genetic similarities to B cell lymphomas, supporting a clonal relationship between B cell neoplasms and a subset of histiocytic sarcomas. These findings support a cooperative role for MAPK, PI3K, and cyclin-CDK4/6-INK4 signaling in the pathogenesis of histiocytic sarcoma and provide a rational basis for targeting these pathways.
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