TY - JOUR
T1 - BRAF and MAP2K1 mutations in Langerhans cell histiocytosis
T2 - A study of 50 cases
AU - Alayed, Khaled
AU - Medeiros, L Jeffrey
AU - Patel, Keyur Pravinchandra
AU - Zuo, Zhuang
AU - Li, Shaoying
AU - Verma, Shalini
AU - Galbincea, John
AU - Cason, R. Craig
AU - Luthra, Rajyalakshmi
AU - Yin, Cheng Cameron
N1 - Funding Information:
Funding/Support: Funding for this study was provided, in part, by the Saudi Arabian Cultural Mission, Riyadh, Saudi Arabia .
Publisher Copyright:
© Published by Elsevier Inc.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Age
KW - BRAF mutation
KW - Immunohistochemistry
KW - Langerhans cell histiocytosis
KW - MAP2K1 mutation
KW - Pyrosequencing
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U2 - 10.1016/j.humpath.2015.12.029
DO - 10.1016/j.humpath.2015.12.029
M3 - Article
C2 - 26980021
AN - SCOPUS:84961837668
SN - 0046-8177
VL - 52
SP - 61
EP - 67
JO - Human Pathology
JF - Human Pathology
ER -