Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France

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.

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Journal
Blood Advances
Published
2025-02-26
DOI
https://doi.org/10.1182/bloodadvances.2024015208
Citations
11
Primary Topic
Histiocytic Disorders and Treatments
Type
article
Field-Weighted Citation Impact
12.81
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article

Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France

Arnaud Pagès, Loïc Ysebaert, Géraldine Salmeron, Jean Donadieu et al.
11 citations
Blood Advances
Histiocytic Disorders and Treatments
12.81
article

Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France

Arnaud Pagès, Loïc Ysebaert, Géraldine Salmeron, Jean Donadieu, Jérémie Dion, Hélène Monjanel, Zofia Hélias‐Rodzewicz, Frédéric Charlotte, Marie Parrens, Gandhi Laurent Damaj, Marzieh Nashvi, Eve-Marie Nazal-Traissac, Sébastien Heritier, Jean‐François Emile, Isabelle Laure Ray-Coquard, Camille Bigenwald, Stéphanie Tardy, Damien Roos‐Weil, Christiane Copie‐Bergman, Tony Marchand, Pierre Khneisser, Ahmed Idbaïh, Julien Haroche, Alexandra Traverse-Glehen, Antoine Néel, Jérôme Razanamahery
article en
11 citations

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.

Blood AdvancesVol. 9(10)
Université Claude Bernard Lyon 1 (FR), Université de Bordeaux (FR), Inserm (FR), Université de Versailles Saint-Quentin-en-Yvelines (FR), Université Paris-Est Créteil (FR), Université Paris-Saclay (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Université Rennes 2 (FR), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Centre Hospitalier Agen - Nérac (FR), Hospices Civils de Lyon (FR), Centre de recherche en Epidémiologie et Santé des Populations (FR), Centre Léon Bérard (FR), Centre Hospitalier Intercommunal de Poissy (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), Health Services and Performance Research Laboratory (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Pitié-Salpêtrière Hospital (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Annecy Genevois (FR), Maison des Sciences sociales et des Humanités de Dijon (FR), Institut du Cerveau (FR), Centre Hospitalier Universitaire de Rennes (FR)
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Openalex Percentile: Top 1%
Histiocytic Disorders and Treatments
12.81
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