TY - JOUR
T1 - Microsecretory Adenocarcinoma
T2 - A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion
AU - Bishop, Justin A.
AU - Weinreb, Ilan
AU - Swanson, David
AU - Westra, William H.
AU - Qureshi, Hina S.
AU - Sciubba, James
AU - Macmillan, Christina
AU - Rooper, Lisa M.
AU - Dickson, Brendan C.
N1 - Publisher Copyright:
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - adenocarcinoma not otherwise specified
KW - polymorphous adenocarcinoma
KW - salivary glands
KW - secretory carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85069888784&partnerID=8YFLogxK
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U2 - 10.1097/PAS.0000000000001273
DO - 10.1097/PAS.0000000000001273
M3 - Article
C2 - 31094920
AN - SCOPUS:85069888784
SN - 0147-5185
VL - 43
SP - 1023
EP - 1032
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 8
ER -