title: BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases.
abstract: Langerhans cell histiocytosis (LCH) is a proliferation of Langerhans cells, often associated with lymphocytes, eosinophils, macrophages, and giant cells. BRAF mutations, usually V600E, have been reported in 40%-70% of cases, and recently, MAP2K1 mutations have been reported in BRAF-negative cases. We assessed 50 cases of LCH for BRAF mutations and assessed a subset of cases for MAP2K1 mutations. The study group included 28 men and 22 women (median age, 36.5 years; range, 1-78 years). BRAF V600E mutation was detected in 8 (16%) cases including 3 (30%) skin, 2 (11%) bone, 1 (50%) colon, 1 (20%) lung, and 1 (33%) extradural, intracranial mass. MAP2K1 mutations were detected in 6 of 13 (46%) BRAF-negative cases including 2 (100%) lymph node, 2 (50%) bone, 1 (25%) skin, and 1 (100%) orbit. Patients with BRAF mutation were younger than patients with wild-type BRAF (median age, 28 versus 38 years; P = .026). The median age of MAP2K1-mutated patients was 34.5 years, similar to patients without MAP2K1 mutation (41 years; P = .368). In agreement with 2 recent studies, we showed a high frequency of MAP2K1 mutations in BRAF-negative LCH cases. Unlike other studies, the overall frequency of BRAF mutation in this cohort is substantially lower than what has been reported in pediatric patients, perhaps because most patients in this study were adults. Moreover, we showed a high concordance between mutational and immunohistochemical analysis for BRAF mutation. There was no statistically significant association between BRAF or MAP2K1 mutation and anatomic site, unifocal versus multifocal presentation, or clinical outcome.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030; Department of Pathology, King Saud University, Riyadh, 11461, Saudi Arabia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Alayed
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Shalini
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: John
authors.initials: J
authors.lastname: Galbincea
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: R Craig
authors.initials: RC
authors.lastname: Cason
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030. Electronic address: cyin@mdanderosn.org.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006646:Histiocytosis, Langerhans-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: Age; BRAF mutation; Immunohistochemistry; Langerhans cell histiocytosis; MAP2K1 mutation; Pyrosequencing