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BRAF mutation leading to central nervous system rosai‐dorfman disease
Author(s) -
Richardson Timothy E.,
Wachsmann Megan,
Oliver Dwight,
Abedin Zahidur,
Ye Diana,
Burns Dennis K.,
Raisanen Jack M.,
Greenberg Benjamin M.,
Hatanpaa Kimmo J.
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25281
Subject(s) - rosai–dorfman disease , emperipolesis , erdheim–chester disease , histiocytosis , histiocyte , langerhans cell histiocytosis , mutation , sanger sequencing , cancer research , biology , pathology , medicine , disease , gene , genetics
Rosai–Dorfman disease (RDD) is an uncommon histiocytic proliferative disorder that can present in nodal, extranodal, or, extremely rarely, in central nervous system (CNS)‐restricted form. RDD is characterized histologically as a non‐Langerhans cell histiocytosis composed of atypical CD68 + /S‐100 + /CD1a – macrophages demonstrating prominent emperipolesis and effacement of the surrounding tissue. Previously thought to represent a reactive process, recent studies have raised the possibility that RDD and other histiocytic lesions, including Erdheim–Chester and Langerhans cell histiocytosis, are clonal processes linked to somatic mutations in the mitogen‐activated protein (MAP) kinase pathway. Herein, we present a fatal case of RDD isolated to the CNS and used a next‐generation targeted gene panel and Sanger sequencing to uncover a pathogenic deletion in the β3‐αC loop of the kinase domain in exon 12 of BRAF . This mutation, previously described in melanoma and Langerhans cell histiocytosis, represents the first BRAF mutation of this kind identified in RDD. These findings support the idea that RDD is a neoplastic condition and raise the possibility that inhibitors of the MAP kinase pathway may be effective in RDD. Ann Neurol 2018;83:147–152