title: BRAF V600E analysis for the differentiation of papillary craniopharyngiomas and Rathke's cleft cysts.
abstract: OBJECTIVE
  The differential diagnosis of cystic epithelial masses of the sellar region, especially the histopathological differentiation of craniopharyngiomas and Rathke's cleft cysts, poses a challenge even to experienced diagnosticians. Recently, BRAF V600E mutations have been described as a genetic hallmark of papillary craniopharyngiomas. We investigated a series of 33 Rathke's cleft cysts to determine the frequency of BRAF V600E mutations and its suitability as an additional diagnostic marker for the differentiation of cystic lesions of the sellar region.
  
  
  METHODS
  Thirty-three Rathke's cleft cysts and 18 papillary craniopharyngiomas were analysed for BRAF mutational status by immunohistochemistry using a monoclonal antibody (VE1) that selectively recognizes the BRAF V600E mutant epitope and additional BRAF pyrosequencing in a subset of samples.
  
  
  RESULTS
  Thirty of 33 specimens diagnosed as Rathke's cleft cysts were negative by VE1 immunohistochemistry and pyrosequencing, whereas in three cysts and in all the 18 papillary craniopharyngiomas, a BRAF V600E mutation was detected. Clinical and histological re-evaluation of the three BRAF V600E mutated cases formerly diagnosed as Rathke's cleft cysts revealed unusual presentations. Two of them were rediagnosed as papillary craniopharyngiomas. The patient of the third case had a history of craniopharyngioma operated 14 years before, and reoperation showed a cystic epithelial lesion with unclear histology.
  
  
  CONCLUSIONS
  The determination of BRAF mutational status is recommended in any cystic sellar lesion and can in most cases be provided by VE1 immunohistochemistry even in specimens of low cellularity. Confirmation by (pyro-)sequencing should be attempted whenever sufficient epithelium is available due to variable staining results.
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Leonille
authors.initials: L
authors.lastname: Schweizer
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.affiliation: Department of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen-Nürnberg, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Hölsken
authors.affiliation: Department of Neurosurgery, International Neuroscience Institute, Hannover, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fahlbusch
authors.affiliation: Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Flitsch
authors.affiliation: Department of Neurosurgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen-Nürnberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.affiliation: Department of Neurosurgery, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen-Nürnberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D020863:Central Nervous System Cysts / Q000235:genetics* / Q000473:pathology; D003397:Craniopharyngioma / Q000235:genetics* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E mutation; Rathke's cleft cysts; VE1 immunohistochemistry; papillary craniopharyngioma; pyrosequencing