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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Pathology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS 250, Memphis, TN, 38105, USA

    Armita Bahrami, James D. Dalton & Bangalore Shivakumar

  2. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Jeffrey F. Krane

Authors
  1. Armita Bahrami
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  2. James D. Dalton
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  3. Bangalore Shivakumar
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  4. Jeffrey F. Krane
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Correspondence to Armita Bahrami.

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Bahrami, A., Dalton, J.D., Shivakumar, B. et al. PLAG1 Alteration in Carcinoma Ex Pleomorphic Adenoma: Immunohistochemical and Fluorescence In Situ Hybridization Studies of 22 Cases. Head and Neck Pathol 6, 328–335 (2012). https://doi.org/10.1007/s12105-012-0353-8

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  • DOI: https://doi.org/10.1007/s12105-012-0353-8

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