title: Oncocytic change in pleomorphic adenoma: molecular evidence in support of an origin in neoplastic cells.
abstract: BACKGROUND
  Cells with oncocytic change (OC) are a common finding in salivary glands (SGs) and in SG tumours. When found within pleomorphic adenomas (PAs), cells with OC may be perceived as evidence of malignancy, and lead to a misdiagnosis of carcinoma ex pleomorphic adenoma (CaExPa).
  
  
  OBJECTIVE
  To describe a case of PA with atypical OC, resembling a CaExPa. A genomewide molecular analysis was carried out to compare the molecular genetic features of the two components and to determine whether the oncocytic cells originated from PA cells, entrapped normal cells, or whether these cells constitute an independent tumour.
  
  
  METHODS
  Representative blocks were immunohistochemically analysed with antibodies raised against cytokeratin (Ck) 5/6, Ck8/18, Ck14, vimentin, p63, alpha-smooth muscle actin (ASMA), S100 protein, anti-mitochondria antibody, beta-catenin, HER2, Ki67, p53 and epidermal growth factor receptor. Typical areas of PA and OC were microdissected and subjected to microarray-based comparative genomic hybridisation (aCGH). Chromogenic in situ hybridisation (CISH) was performed with in-house generated probes to validate the aCGH findings.
  
  
  RESULTS
  PA cells showed the typical immunohistochemical profile, including positivity for Ck5/6, Ck8/18, Ck14, vimentin, ASMA, S100 protein, p63, epidermal growth factor receptor and beta-catenin, whereas oncocytic cells showed a luminal phenotype, expression of anti-mitochondria antibody and reduced beta-catenin staining. Both components showed low proliferation rates and lacked p53 reactivity. aCGH revealed a similar amplification in both components, mapping to 12q13.3-q21.1, which was further validated by CISH. No HER2 gene amplification or overexpression was observed. The foci of oncocytic metaplasia showed an additional low-level gain of 6p25.2-p21.31.
  
  
  CONCLUSIONS
  The present data demonstrate that the bizarre atypical cells of the present case show evidence of clonality but no features of malignancy. In addition, owing to the presence of a similar genome amplification pattern in both components, it is proposed that at least in some cases, OC may originate from PA cells.
authors.affiliation: Royal Surrey County Hospital, University of Surrey, Guildford, UK.
authors.forename: Silvana
authors.initials: S
authors.lastname: Di Palma
authors.forename: Maryou B K
authors.initials: MB
authors.lastname: Lambros
authors.forename: Kay
authors.initials: K
authors.lastname: Savage
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.forename: Tim
authors.initials: T
authors.lastname: Dexter
authors.forename: Marjan
authors.initials: M
authors.lastname: Iravani
authors.forename: Kerry
authors.initials: K
authors.lastname: Fenwick
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D006801:Humans; D042282:Microdissection / Q000379:methods; D009363:Neoplasm Proteins / Q000378:metabolism; D009693:Nucleic Acid Hybridization / Q000379:methods; D024862:Oxyphil Cells / Q000473:pathology*; D010307:Parotid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins