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. 2024 May 1;48(5):551-561.
doi: 10.1097/PAS.0000000000002206. Epub 2024 Mar 18.

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion

Ziyad Alsugair  1 , Jimmy Perrot  1 , Françoise Descotes  2 , Jonathan Lopez  2 , Anne Champagnac  3 , Daniel Pissaloux  3   4 , Claire Castain  5 , Mihaela Onea  6 , Philippe Céruse  7 , Pierre Philouze  7 , Charles Lépine  8   9 , Marie-Delphine Lanic  10   11 , Marick Laé  10   11 , Valérie Costes-Martineau  12 , Nazim Benzerdjeb  1   13 ; and REFCOR Members
Collaborators, Affiliations

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion

Ziyad Alsugair et al. Am J Surg Pathol. .

Abstract

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

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