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

Abstract

Key Points Some 10.1% of adults with non–Langerhans cell histiocytosis have a concomitant myeloid neoplasm with each often harboring distinct mutations. The presence of distinct kinase mutations in histiocytosis and myeloid neoplasms resulted in discordant responses to targeted therapy.

Erdheim-Chester disease associated with chronic myelomonocytic leukemia harboring the same clonal mutation

“…9 However, the clonal relationship between the two diseases has not been clearly demonstrated. 8 We report herein three cases of xanthelasma-like lesions fulfilling clinical, histological and molecular criteria for ECD associated with CMML with a proven clonal relationship between the skin lesions and CMML cells based on molecular analyses.…”

“…In the only patient who had NGS targeted sequencing in both ECD and CMML cells, the same NRAS mutations were identified in perirenal tissue suggesting that the association is not restricted to ECD with limited skin involvement as in our cases. 8 Moreover, recently, Ghobadi et al identified the same BRAF-V600E mutation in the blasts from BM aspirate of an acute myeloid leukemia (AML) M5 and in ECD cells from a lung biopsy with bone, peri-aortic infiltration, lung, neurological and retroperitoneal involvement. 11 Moreover, using whole exome sequencing, they confirmed that the ECD and AML had multiple shared mutations and arose from the same cell of origin with additional mutations mostly for AML cells.…”

“…Pauline Bonnet, *1 François Chasset, *1 Philippe Moguelet, 2 Noémie Abisror, 3 Raphaël Itzykson, 4 Jean-David Bouaziz, 5 Pierre Hirsch, 6 Annick Barbaud, 1 Julien Haroche, 7 Arsène Mekinian, 3 Zofia Hélias-Rodzewicz, 8 Emmanuelle Clappier, 9 Pierre Fenaux, 4 Olivier Fain, 3 Abdellatif Tazi, 10 Jean-François Emile 8 Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at www.haematologica.org.…”

BRAF-V600E–mutated Rosai-Dorfman-Destombes disease and Langerhans cell histiocytosis with response to BRAF inhibitor

“…In adults, various presentations of mixed histiocytosis with LCH/Erdheim-Chester disease (ECD) sharing a BRAF-V600E mutation have been reported and is 1 reason for reclassifying them as L-group lesions. 2,26 However, in rare adult cases of mixed R-and L-group lesions (ie, isolated RDD with ECD 27 or LCH-ECD-RDD with myeloid fibrosis 28 ), none have demonstrated a BRAF-V600E mutation and only a few demonstrate other MAPK mutations. 27 In reported mixed RDD/LCH cases (Table 1), none have documented BRAF mutations.…”

Bone marrow findings in Erdheim-Chester disease: increased prevalence of chronic myeloid neoplasms

“…In the previous study evaluating this question, the prevalence of myeloid neoplasms in non-LCH patients was much higher at 10.1%. 6 There may be several reasons to account for this difference. The prior study included patients from a cancer center in the United States and a histiocytosis referral center in France, with a higher percentage of myeloid neoplasms from the former (15.3%) as compared to the latter (8.6%).…”