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Oncocytic change in pleomorphic adenoma: molecular evidence in support of an origin in neoplastic cells
  1. Silvana Di Palma1,
  2. Maryou B K Lambros2,
  3. Kay Savage2,
  4. Chris Jones3,
  5. Alan Mackay2,
  6. Tim Dexter2,
  7. Marjan Iravani2,
  8. Kerry Fenwick2,
  9. Alan Ashworth2,
  10. Jorge S Reis-Filho2
  1. 1Royal Surrey County Hospital, University of Surrey, Guildford, UK
  2. 2The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
  3. 3Section of Paediatric Oncology, Institute of Cancer Research, Sutton, UK
  1. Correspondence to:
 Dr J S Reis-Filho
 The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK; jorgerf{at}


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).

Aim: 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.

Materials and methods: Representative blocks were immunohistochemically analysed with antibodies raised against cytokeratin (Ck) 5/6, Ck8/18, Ck14, vimentin, p63, α-smooth muscle actin (ASMA), S100 protein, anti-mitochondria antibody, β-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 β-catenin, whereas oncocytic cells showed a luminal phenotype, expression of anti-mitochondria antibody and reduced β-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.

Conclusion: 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.

  • aCGH, microarray-based comparative genomic hybridisation
  • ASMA, α-smooth muscle actin
  • BAC, bacterial artificial chromosome
  • CaExPa, carcinoma ex pleomorphic adenoma
  • CDK4, cyclin-dependent kinase 4
  • CISH, chromogenic in situ hybridisation
  • Ck, cytokeratin
  • EGFR, epidermal growth factor receptor
  • OC, oncocytic change
  • OM, oncocytic metaplasia
  • PA, pleomorphic adenoma
  • SDS, sodium dodecyl sulphate
  • SG, salivary gland
  • SSC, saline sodium citrate

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  • Published Online First 7 February 2006

  • Competing interests: None declared.