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Microsecretory Adenocarcinoma

A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion

Bishop, Justin A. MD*,†; Weinreb, Ilan MD‡,§; Swanson, David BSc§,∥; Westra, William H. MD; Qureshi, Hina S. MD#; Sciubba, James DMD**; MacMillan, Christina MD§,∥; Rooper, Lisa M. MD; Dickson, Brendan C. MSc, MD§,∥

The American Journal of Surgical Pathology: August 2019 - Volume 43 - Issue 8 - p 1023–1032
doi: 10.1097/PAS.0000000000001273
Original Articles

Salivary gland adenocarcinoma not otherwise specified (NOS) is a heterogenous group, likely containing distinct tumors not yet characterized. A growing number of low to intermediate-grade salivary carcinomas are now known to harbor tumor-specific gene fusions. On occasion, identifying a novel fusion allows for recognition of a new salivary tumor type, in addition to representing a potential diagnostic tool. We sought to characterize a distinctive salivary gland adenocarcinoma that would previously have been regarded as adenocarcinoma NOS. On the basis of the recognition of 5 morphologically identical, distinct low-grade salivary adenocarcinomas, we used targeted RNA sequencing (RNA-Seq) to determine whether these could be differentiated from other fusion-associated salivary gland tumors. RNA-Seq was performed on all 5 low-intermediate grade adenocarcinomas NOS with near-identical histologic appearances, as well as 23 low-intermediate grade control adenocarcinoma NOS cases that did not resemble the index cases. All 5 index cases harbored a novel MEF2C-SS18 gene fusion, which was independently confirmed by reverse transcriptase-polymerase chain reaction. The MEF2C-SS18-positive cases arose in the oral cavity (4/5) and parotid gland (1/5) of 3 women and 2 men ranging from 21 to 80 years (mean: 46) and shared near-identical histologic features: intercalated duct-like cells with eosinophilic to clear cytoplasm and small, uniform oval nuclei, infiltrative microcysts and cords, abundant intraluminal secretions, and cellular fibromyxoid stroma. Mitotic rates were low; necrosis was absent. All MEF2C-SS18-positive tumors were positive for S100 and p63 and negative for p40, smooth muscle actin, calponin, and mammaglobin. One of the 23 control cases, a parotid tumor, was found to contain a SS18-ZBTB7A gene fusion; it demonstrated similar, but not identical histologic and immunophenotypic features compared with the MEF2C-SS18 cases. The remaining control cases were negative for SS18 and MEF2C rearrangements. A novel MEF2C-SS18 gene fusion and unique histologic and immunophenotypic features characterize a heretofore undefined low-grade salivary adenocarcinoma for which we propose the term “microsecretory adenocarcinoma.” RNA-Seq helped establish this entity as a distinct tumor type, and identified one possibly related case with a different SS18-related fusion. The recognition of microsecretory adenocarcinoma and its separation from other adenocarcinomas NOS will facilitate a more complete understanding of the clinical and pathologic characteristics of this previously unrecognized neoplasm.

*Department of Pathology, UT Southwestern Medical Center, Dallas, TX

Department of Pathology, The Johns Hopkins Hospital

**Milton J. Dance Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD

Department of Pathology, University Health Network

§Department of Laboratory Medicine and Pathobiology, University of Toronto

Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada

Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY

#ProDia Laboratories, Charlottesville, VA

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: Justin A. Bishop, MD, University of Texas Southwestern Medical Center, 6201 Harry Hines Blvd., Dallas, TX 75390-9073 (e-mail:

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