Molecular analysis of BRAF V600E mutation in multiple nodules of pulmonary Langerhans cell histiocytosis

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare, smoking-related histiocytic disorder with variable clinical symptoms. Like in other non-pulmonary Langerhans cell proliferations, PLCH has recently been shown to harbour BRAF V600E mutations in a significant subset of cases, thus challenging...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2017-04, Vol.470 (4), p.429-435
Main Authors: Dimmler, Arno, Geddert, Helene, Werner, Martin, Faller, Gerhard
Format: Article
Language:English
Subjects:
Adult
Aged
DNA Mutational Analysis - methods
Female
Histiocytosis, Langerhans-Cell - genetics
Histiocytosis, Langerhans-Cell - pathology
Humans
Immunohistochemistry
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Original Article
Pathology
Polymerase Chain Reaction - methods
Proto-Oncogene Proteins B-raf - genetics
Sensitivity and Specificity
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Summary:Pulmonary Langerhans cell histiocytosis (PLCH) is a rare, smoking-related histiocytic disorder with variable clinical symptoms. Like in other non-pulmonary Langerhans cell proliferations, PLCH has recently been shown to harbour BRAF V600E mutations in a significant subset of cases, thus challenging the concept of PLCH being a reactive disorder. Here, we analysed 38 formalin-fixed and paraffin-embedded PLCH nodules of nine patients for BRAF mutation using two different molecular methods. Using pyrosequencing and allele-specific quantitative PCR (AS-PCR), BRAF V600E mutations were found in 16/38 (42%) and 31/37 (84%) nodules, respectively. Analysing different nodules of the same patients with pyrosequencing 3/6 patients showed a concordant BRAF mutation status. When allele-specific quantitative PCR was used, condordant results were found in 5/6 patients. Our findings clearly indicate that (a) the sensitivity of the method used is crucial in analysing BRAF mutation status, (b) AS-PCR is more sensitive in detecting BRAF V600E mutations than pyrosequencing, (c) BRAF mutation is frequent and might play a key role in the pathogenesis of PLCH and (d) PLCH is a true neoplastic disease.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-017-2092-4