Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts Journal Article


Authors: Katabi, N.; Ghossein, R.; Ho, A.; Dogan, S.; Zhang, L.; Sung, Y. S.; Antonescu, C. R.
Article Title: Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts
Abstract: Carcinoma ex-pleomorphic adenoma (CA ex-PA) is a malignant salivary gland tumor that arises in association with pleomorphic adenoma (PA). Both PA and CA ex-PA have a broad spectrum of histology, and distinction from their histologic mimics may be difficult based on morphology alone. PLAG1 and HMGA2 abnormalities are the most common genetic events in both PA and CA ex-PA; however, the use of PLAG1 and HMGA2 as adjunct molecular tests has not been well established. Fluorescence in situ hybridization for PLAG1 and HMGA2 was performed on 22 CA ex-PA (10 myoepithelial carcinomas [MECAs], 10 salivary duct carcinomas [SDCs], 1 carcinoma with squamoglandular features, and 1 mixed MECA-adenocarcinoma not otherwise specified), 20 de novo carcinomas (11 MECAs and 9 SDCs), 16 PAs, and 11 PA-histologic mimics. All except 3 CAs ex-PA (86%) were positive for PLAG1 or HMGA2 rearrangements/amplifications. In contrast, 18 (90%) of 20 de novo carcinomas lacked abnormalities in PLAG1 or HMGA2 (P <.01). PLAG1 or HMGA2 rearrangements were identified in 6 (67%) of 9 hypocellular myxoid PAs and in 2 (29%) of 7 cellular PAs. Furthermore, all morphologic mimics of PA were negative for PLAG1 or HMGA2. PLAG1 and HMGA2 rearrangements are the most common genetic events in CA ex-PA regardless of the histologic subtype. Unlike CA ex-PA, de novo carcinomas were negative for PLAG1 and HMGA2. Interestingly, rearrangements of PLAG1/HMGA2 were identified in most hypocellular PAs but only in a small subset of cellular PAs. Fluorescence in situ hybridization for PLAG1 or HMGA2 can be used to distinguish between PA and CA ex-PA and their morphologic mimics.
Keywords: immunohistochemistry; adult; clinical article; aged; middle aged; unclassified drug; oncoprotein; squamous cell carcinoma; adenocarcinoma; fluorescence in situ hybridization; gene rearrangement; salivary gland cancer; zinc finger protein; myoepithelial carcinoma; pleomorphic adenoma; salivary duct carcinoma; carcinoma ex pleomorphic adenoma; very elderly; high mobility group a2 protein; human; male; female; article; hmga2; plag1; plag1 protein; carcinoma with squamoglandular feature; squamoglandular carcinoma
Journal Title: Human Pathology
Volume: 46
Issue: 1
ISSN: 0046-8177
Publisher: Elsevier Inc.  
Date Published: 2015-01-01
Start Page: 26
End Page: 33
Language: English
DOI: 10.1016/j.humpath.2014.08.017
PROVIDER: scopus
PUBMED: 25439740
PMCID: PMC4768723
DOI/URL:
Notes: Export Date: 2 January 2015 -- Source: Scopus
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MSK Authors
  1. Ronald A Ghossein
    482 Ghossein
  2. Cristina R Antonescu
    895 Antonescu
  3. Nora Katabi
    303 Katabi
  4. Snjezana Dogan
    187 Dogan
  5. Alan Loh Ho
    237 Ho
  6. Lei Zhang
    194 Zhang
  7. Yun Shao Sung
    124 Sung