title: Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.
abstract: Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Stevens
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Andra O
authors.initials: AO
authors.lastname: Kovalovsky
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Velosa
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Surgery, Mount Sinai Hospital, Icahn School of Medicine, New York, NY, USA.
authors.forename: Randall P
authors.initials: RP
authors.lastname: Owen
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Bell
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.affiliation: Human Genetics Laboratory, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Althof
authors.affiliation: Human Genetics Laboratory, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jennifer N
authors.identifier: 000000034576025X
authors.initials: JN
authors.lastname: Sanmann
authors.affiliation: Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Sweeny
authors.affiliation: Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Carroll
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bullock
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Brandwein-Gensler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D018118:Chloride Channels / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D000069295:Mammary Analogue Secretory Carcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D009418:S100 Proteins / Q000032:analysis; D012468:Salivary Gland Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D060765:Secretoglobins / Q000032:analysis; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D009363:Neoplasm Proteins; D050783:Proto-Oncogene Proteins c-ets; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D009418:S100 Proteins; D060765:Secretoglobins; D000097764:ETS Translocation Variant 6 Protein; C476213:ANO1 protein, human; C508053:ERBB2 protein, human