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Blood. 2017 Aug 24;130(8):1007-1013. doi: 10.1182/blood-2017-01-761718. Epub 2017 Jul 5.

High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis.

Author information

1
Service de Médecine Interne 2, Institut E3M, Centre de Références des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Histiocytoses, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie, Paris, France.
2
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY.
3
EA4340, Versailles University, Paris-Saclay University, Boulogne, France.
4
Pathology Service, Hôpital universitaire Ambroise Paré, AP-HP, Boulogne, France.
5
UMR1170, INSERM and Institute Gustave Roussy, Villejuif, France.
6
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH.
7
Department of Pathology.
8
Department of Radiology, and.
9
Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
10
Department of Internal Medicine, Foch Hospital, Suresnes, France.
11
Department of Internal Medicine, Croix Saint-Simon Hospital, Paris, France.
12
Department of Internal Medicine and Immunology, and.
13
Department of Biological Hematology, University Hospital La Pitié Salpêtrière, AP-HP, Paris, France.
14
Gustave Roussy, Paris-Saclay University, Genomic Platform UMS AMMICA, Villejuif, France; and.
15
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.

Abstract

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.

PMID:
28679734
PMCID:
PMC5570678
DOI:
10.1182/blood-2017-01-761718
[Indexed for MEDLINE]
Free PMC Article

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