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

Mastropolo, Rosemarie; Close, Allison; Allen, Steven W.; McClain, Kenneth L.; Maurer, Scott H.; Picarsic, Jennifer

doi:10.1182/bloodadvances.2019000093

Cited by 34 publications

(26 citation statements)

References 32 publications

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“…Scattered RDD-like cells with emperipolesis and variable light S100 staining has been previously noted in cutaneous JXG-family lesions [33, 54]. Furthermore BRAF V600E mutations have also been identified in rare cases of RDD [25, 44], including a variant BRAF mutation with CNS disease [52], which further emphasizes that morphology combined with molecular are useful for accurate diagnosis.…”

Section: Discussionmentioning

confidence: 83%

“…In the post-BRAF era, we now turn our attention to the molecular classification of histiocytic neoplasms as an area of ongoing, active investigation, which now includes extracutaneous JXG with BRAF V600E and MAPK pathway mutations, in addition to LCH and ECD with BRAF V600E mutations, and even rare reports of RDD with BRAF V600E [25, 44]. Thus, the question of whether the L-group histiocytic group should include only LCH/ECD or whether a more inclusive category of “MAPK-pathway activated histiocytoses” should now exist for all groups will need further discussion.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the current revised classification of histiocytes [21] has created a divide between the JXG family of neoplasms with molecular alterations (L-group) and those without molecular alterations (C-group). Standing alone, this grouping does not have particular clinical significance, especially given that both C-group and even R-group histiocytic lesions now also harbor MAPK-pathway activated mutations [16, 25, 28, 44, 49, 52]. Furthermore, the World Health Organization (WHO) recommends that CNS neoplasms have an initial morphologic report followed by an integrated final diagnosis after molecular studies are completed [42].…”

Section: Introductionmentioning

confidence: 99%

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BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

Picarsic

Pysher

Zhou

et al. 2019

acta neuropathol commun

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The family of juvenile xanthogranuloma family neoplasms (JXG) with ERK-pathway mutations are now classified within the “L” (Langerhans) group, which includes Langerhans cell histiocytosis (LCH) and Erdheim Chester disease (ECD). Although the BRAF V600E mutation constitutes the majority of molecular alterations in ECD and LCH, only three reported JXG neoplasms, all in male pediatric patients with localized central nervous system (CNS) involvement, are known to harbor the BRAF mutation. This retrospective case series seeks to redefine the clinicopathologic spectrum of pediatric CNS-JXG family neoplasms in the post-BRAF era, with a revised diagnostic algorithm to include pediatric ECD. Twenty-two CNS-JXG family lesions were retrieved from consult files with 64% (n = 14) having informative BRAF V600E mutational testing (molecular and/or VE1 immunohistochemistry). Of these, 71% (n = 10) were pediatric cases (≤18 years) and half (n = 5) harbored the BRAF V600E mutation. As compared to the BRAF wild-type cohort (WT), the BRAF V600E cohort had a similar mean age at diagnosis [BRAF V600E: 7 years (3–12 y), vs. WT: 7.6 years (1–18 y)] but demonstrated a stronger male/female ratio (BRAF V600E: 4 vs WT: 0.67), and had both more multifocal CNS disease ( BRAFV600E: 80% vs WT: 20%) and systemic disease (BRAF V600E: 40% vs WT: none). Radiographic features of CNS-JXG varied but typically included enhancing CNS mass lesion(s) with associated white matter changes in a subset of BRAF V600E neoplasms. After clinical-radiographic correlation, pediatric ECD was diagnosed in the BRAF V600E cohort. Treatment options varied, including surgical resection, chemotherapy, and targeted therapy with BRAF-inhibitor dabrafenib in one mutated case. BRAF V600E CNS-JXG neoplasms appear associated with male gender and aggressive disease presentation including pediatric ECD. We propose a revised diagnostic algorithm for CNS-JXG that includes an initial morphologic diagnosis with a final integrated diagnosis after clinical-radiographic and molecular correlation, in order to identify cases of pediatric ECD. Future studies with long-term follow-up are required to determine if pediatric BRAF V600E positive CNS-JXG neoplasms are a distinct entity in the L-group histiocytosis category or represent an expanded pediatric spectrum of ECD.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

Picarsic

Pysher

Zhou

et al. 2019

acta neuropathol commun

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“…Anti-BRAF V600E immunohistochemistry was strongly positive in both RDD and LCH, and BRAF p.V600E mutation was detected on peripheral blood mononuclear cells. 20 Richardson et al 19 demonstrated a single somatic pathogenic mutation in exon 12 of the BRAF gene (p.486-491del) Types of lymphoma include Hodgkin's lymphoma-classic (8) 25 26 35 and nodular lymphocyte predominant (8) 35 36 and non-Hodgkin's lymphoma-follicular (2), 25 T cell (3), [29][30][31] small lymphocytic lymphoma (2), 35 37 Mantle cell (1), 38 marginal zone lymphoma (3), 35 39 40 diffuse large B cell lymphoma (4), 27 28 41 42 mycosis fungoides (1) 32 and other (large cell immunoblastic and small non-cleaved, 2). 33 34 Types of leukaemia include acute myeloid leukaemia (1) 43 and acute lymphoblastic leukaemia (2).…”

Section: Aetiopathogenesismentioning

confidence: 99%

Rosai-Dorfman disease: an overview

2020

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ContextRosai-Dorfman disease is an uncommon histiocytic disorder most frequently presenting as bilateral cervical lymphadenopathy in children and young adults. Extranodal disease occurs in a significant proportion of patients. It has been recently classified as part of the ‘R group’ of histiocytoses by the Histiocyte Society in 2016. Cutaneous Rosai-Dorfman disease is regarded as a separate disease entity that falls into the ‘C group’ of histiocytoses according to this classification system. The pathogenesis was previously poorly understood; however, recent evidence demonstrating clonality in a subset of cases raises the possibility of a neoplastic process. A possible association with IgG4-related disease remains controversial.ObjectivesTo provide a comprehensive review of Rosai-Dorfman disease, including nodal, extranodal and cutaneous forms, with a particular emphasis on new insights into the possible clonal nature of the disease; to discuss the recently revised classification of the histiocytoses by the Histiocyte Society; and to summarise the findings from the literature regarding the controversial association with IgG4-related disease.Data sourcesThis review is based on published peer-reviewed English literature.ConclusionsClassic Rosai-Dorfman disease, which may be sporadic or familial, is considered a separate entity from cutaneous disease, which is reflected in the revised classification of histiocytoses. An increase in IgG4-positive plasma cells may be seen in Rosai-Dorfman disease. This finding in isolation is of limited significance and should be interpreted with caution. Studies investigating the molecular profile of the disease show that in at least a subset of cases the disease is a clonal process. The classification of Rosai-Dorfman disease is therefore likely to change as our understanding of the aetiopathogenesis evolves.

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“…By and large, these somatic alterations affect the RAS-MAPK pathway, with the frequency of specific genetic defects varying between disorders. For example, although the BRAF V600E mutation is identified in approximately one-half of all cases of LCH and Erdheim-Chester disease, 7,17 it is rare in Rosai-Dorfman disease (RDD) 18,19 and even rarer in JXG. 20,21 An increasing number of studies in the literature describe the somatic mutations other than BRAF V600E found in JXG tumors.…”

Section: Genomic Testingmentioning

confidence: 99%

Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion

Eissa

Clay

Santiago³

et al. 2020

Blood Advances

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

Abstract: Key Points Demonstration of BRAF-V600E in Rosai-Dorfman-Destombes disease requires sensitive molecular assays and molecular-based tissue immunostain. BRAF-V600E blood testing is important for disease-monitoring BRAF-mutated histiocytosis and can guide inhibitor treatment plans.

Cited by 34 publications

References 32 publications

BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

Rosai-Dorfman disease: an overview

Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion

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