Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Malignant histiocytoses (MH) are rare and poorly understood cancers, with no established therapeutic guidelines. We conducted a national retrospective study of MH diagnosed in France between 2000 and 2023. All cases underwent centralized histological review, and several malignant tumors with a stroma highly enriched in histiocytes were excluded. In total, 141 patients were included, with a median age of 62 years (range, 1-87). The cases comprised either primary MH (64%) or MH associated with other hematologic malignancies (36%). Phenotypes corresponded to histiocytic (43%), interdigitating dendritic cell (37%) or Langerhans cell (12%) sarcomas, or high-grade indeterminate dendritic cell tumors (10%), as per the World Health Organization classification. Tumor cells were almost universally positive for CSF1R and PU.1, and 85% showed phosphorylated extracellular signal-regulated kinase positivity. Next-generation sequencing was performed in 75 cases. Mutations in the MAPK pathway were more frequent in secondary compared with primary MH (90% vs 55%; P = .0012). PTPN11 mutations were exclusively observed in primary MH (P = .0035). Mutations in genes related to DNA methylation mechanisms (TET2, ASXL1, DNMT3A) and TP53 were present in 20% and 14% of cases, respectively. Although therapeutic regimens varied considerably, our results demonstrate that surgical resection in localized cases, and the use of BRAF or MEK inhibitors achieved the highest complete response rates, at 63% and 21%, respectively. The prognosis remains poor, with a 5-year overall survival rate of 31%, which is comparable to that of T/natural killer cell lymphomas. Prospective follow-up and a standardized treatment approach in specialized reference centers are crucial to improving patient survival. This trial was registered at www.clinicaltrials.gov as #NCT04437381.