Head and Neck Pathology

, Volume 6, Issue 3, pp 328–335 | Cite as

PLAG1 Alteration in Carcinoma Ex Pleomorphic Adenoma: Immunohistochemical and Fluorescence In Situ Hybridization Studies of 22 Cases

  • Armita BahramiEmail author
  • James D. Dalton
  • Bangalore Shivakumar
  • Jeffrey F. Krane
Original Paper


Carcinoma ex pleomorphic adenoma (CA-ex-PA) may arise with nearly any histologic subtype of carcinoma of the salivary gland. In the absence of recognizable residual pleomorphic adenoma (PA) or a prior history of PA, distinction of CA-ex-PA from morphologically similar de novo carcinomas may be difficult. Oncogenic rearrangement of PLAG1 (pleomorphic adenoma gene 1) has been established in PA; however, it has not yet been proven that PLAG1 alteration persists in carcinomas developed from preceding PA. We evaluated 22 histologically diverse CA-ex-PA by immunohistochemistry for PLAG1, and/or by FISH targeting PLAG1. Of these, 17 cases were immunoreactive (1+ to 3+) and 5 were immunonegative/rare positive for PLAG1. For comparison, 39 various salivary gland neoplasms were immunostained for PLAG1, of which all scored negative/rare positive. Twelve of 19 CA-ex-PA analyzed by PLAG1 FISH (63 %) were positive for gene rearrangement, 2 showed only a trisomy/polysomy profile, and 5 had a normal pattern. One FISH-positive tumor showed amplification of PLAG1. One of 3 cases analyzed for HMGA2 FISH was positive for gene rearrangement. In our series, the majority of CA-ex-PA harbored altered PLAG1 or HMGA2 genes detectable by FISH. While PLAG1 immunostain was specific for CA-ex-PA against other carcinomas, its application as a standalone discriminatory test was limited by variable expression. We conclude that most CA-ex-PA, regardless of morphologic subtype, carry altered PLAG1 or HMGA2 genes, and that FISH for PLAG1, along with immunohistochemistry for PLAG1, may help discriminate CA-ex-PA from its de novo carcinoma counterpart.


Carcinoma ex pleomorphic adenoma PLAG1 Fluorescence in situ hybridization Immunohistochemistry Salivary gland 



This work was supported in part by the American Lebanese Syrian Associated Charities (ALSAC). The study was performed with the approval of the Institutional Review Boards of St. Jude Children’s Research Hospital and Partners Health Care. IRB numbers: NR10-130 and 2010-P-001957/1.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Armita Bahrami
    • 1
    Email author
  • James D. Dalton
    • 1
  • Bangalore Shivakumar
    • 1
  • Jeffrey F. Krane
    • 2
  1. 1.Department of PathologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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