title: Targeted BRAF and CTNNB1 next-generation sequencing allows proper classification of nonadenomatous lesions of the sellar region in samples with limiting amounts of lesional cells.
abstract: OBJECTIVE
  To assess the role of high sensitivity next-generation sequencing (NGS) of CTNNB1 for the diagnosis of adamantinomatous craniopharyngiomas (aCPs) and of BRAF for that of papillary CPs (pCPs) in routinely processed surgical samples of non-adenomatous sellar lesions.
  
  
  METHODS
  Forty-five cases of patients operated for non-adenomatous masses of the sellar region between 2004 and 2014 were retrieved from the files of the Anatomic Pathology unit of the Bellaria Hospital in Bologna, Italy. BRAF and CTNNB1 mutation status was analyzed by NGS in samples smaller than 1 cm(3) and histological re-evaluation was performed on all cases.
  
  
  RESULTS
  CTNNB1 mutation analysis showed a sensitivity of 86.7 % and a specificity of 96.2 % for the diagnosis of aCPs. The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1 S47R lead to histological re-evaluation and reclassification of the lesion as aCP. BRAF mutation analysis had a sensitivity of 76.9 % and a specificity of 96.4 % for the diagnosis of pCPs. The specificity increased to 100 % considering that in one case, initially classified as a Rathke cyst, the identification of BRAF V600E lead to histological re-evaluation and reclassification of the lesion as pCP.
  
  
  CONCLUSIONS
  This study confirms the diagnostic relevance of the molecular alterations recently identified in aCPs and pCPs and shows how the identification of BRAF and CTNNB1 mutations can be instrumental for the proper classification of samples that contain limiting amounts of diagnostic lesional tissue.
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Anatomic Pathology, Bellaria Hospital, University of Bologna, Bologna, Italy. gianluca.marucci@ausl.bologna.it.
authors.forename: Gianluca
authors.identifier: http://orcid.org/0000-0003-4508-3359
authors.initials: G
authors.lastname: Marucci
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Anatomic Pathology, Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: de Biase
authors.affiliation: Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Zoli
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Faustini-Fustini
authors.affiliation: Department of Neuroradiology, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacci
authors.affiliation: ENT Department, Azienda USL, Bologna, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pasquini
authors.affiliation: Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Molecular Biology Unit, Bellaria Hospital, Bologna, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Visani
authors.affiliation: Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, Bologna, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Mazzatenta
authors.affiliation: Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Frank
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Anatomic Pathology, Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003397:Craniopharyngioma / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000175:diagnosis* / Q000209:etiology*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Adamantinomatous craniopharyngioma; BRAF; Beta-catenin; CTNNB1; Papillary craniopharyngioma; Rathke cleft cyst