Microsecretory Adenocarcinoma: A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion
| Autor: | Lisa M. Rooper, David Swanson, William H. Westra, Ilan Weinreb, Christina MacMillan, Justin A. Bishop, James J. Sciubba, Brendan C. Dickson, Hina S. Qureshi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Calponin Biology Adenocarcinoma Pathology and Forensic Medicine Fusion gene 03 medical and health sciences Young Adult 0302 clinical medicine Mammaglobin Proto-Oncogene Proteins medicine Biomarkers Tumor Humans Aged 80 and over Salivary gland MEF2 Transcription Factors Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis RNA Middle Aged medicine.disease Salivary Gland Neoplasms Immunohistochemistry Parotid gland Repressor Proteins 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Surgery Salivary Gland Adenocarcinoma Female Anatomy Gene Fusion Neoplasm Grading |
| Zdroj: | The American journal of surgical pathology. 43(8) |
| ISSN: | 1532-0979 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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