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Metastasizing Pleomorphic Adenoma

Recurrent PLAG1/HMGA2 Rearrangements and Identification of a Novel HMGA2-TMTC2 Fusion

Wasserman, Jason K. MD, PhD, FRCPC*; Dickson, Brendan C. MD, MSc, FRCPC†,‡; Smith, Adam PhD, FCCMG‡,§; Swanson, David BSc†,‡; Purgina, Bibianna M. MD, FRCPC*; Weinreb, Ilan MD, FRCPC‡,∥

The American Journal of Surgical Pathology: August 2019 - Volume 43 - Issue 8 - p 1145–1151
doi: 10.1097/PAS.0000000000001280
Original Articles
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Pleomorphic adenoma (PA) is the most common salivary gland neoplasm. On a molecular level PA is characterized by a translocation involving PLAG1 or HMGA2. PA is considered to be a benign tumor although it can undergo malignant transformation. Alternatively, cases of histologically benign PA “metastasizing” to lymph nodes or distant body sites are well documented. Several theories have been proposed to explain this behavior. However, there is a lack of molecular data available to assess the relationship of metastasizing PA (MPA) and their benign counterparts. In this study we describe 4 cases of MPAs and perform the first molecular study linking them to conventional PA. The index case was identified in the course of routine clinical practice, while the other cases were retrieved from the archives of the authors. Slides were reviewed to confirm the diagnosis of both the primary/recurrent tumor and the metastasis. Fluorescence in situ hybridization (FISH) was performed in all cases and RNA sequencing was performed on the index case. In all cases there was a history of recurrent PA involving the parotid. Lymph node metastases were identified in 2 cases; non–lymph node metastases were identified in 3 cases. All the metastases were histologically benign. RNA sequencing performed on the index case demonstrated a novel HMGA2-TMTC2 translocation, which was confirmed by separate FISH break-apart assays for both genes. FISH performed on the remaining cases demonstrated rearrangement of PLAG1 in all 3 cases. This study demonstrates that MPA harbors the same disease-defining molecular hallmark as their benign counterparts.

*Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital/University of Ottawa

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital

Department of Laboratory Medicine and Pathobiology, University of Toronto

§Laboratory Medicine Program, University Health Network

Department of Pathology, University Health Network, Toronto, ON, Canada

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.

Correspondence: Ilan Weinreb, MD, FRCPC, Department of Anatomical Pathology, University Health Network, Toronto General Hospital Site, 11th Floor, Rm. 11E403, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4 (e-mail: Ilan.weinreb@uhn.ca).

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