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      Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features

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          Abstract

          Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4 th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

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          Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.

          Marie Geierová, Ilan Weinreb, Ivo Stárek … (2010)
          We present a series of 16 salivary gland tumors with histomorphologic and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, and displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff, mucicarmine, MUC1, MUC4, and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor, we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21 to 75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged from 3 months to 10 years. Four patients suffered local recurrences. Two patients died, 1 of them owing to multiple local recurrences with extension to the temporal bone, and another owing to metastatic dissemination to cervical lymph nodes, pleura, pericardium, and lungs. We have shown a t(12;15) (p13;q25) ETV6-NTRK3 translocation in all but one case of MASC suitable for analysis. One case was not analyzable and another was not available for testing. This translocation was not found in any conventional salivary AciCC (12 cases), nor in other tumor types including pleomorphic adenoma (1 case) and low-grade cribriform cystadenocarcinoma (1 case), whereas ETV6-NTRK3 gene rearrangements were proven in all 3 tested cases of mammary secretory carcinoma. Thus, our results strongly support the concept that MASC and AciCC are different entities.
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            Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion.

            Alena Skalova, Tomáš Vaněček, Roderick H W Simpson … (2016)
            ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.
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              Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands.

              Adel Assaad, Simion Chiosea, Christopher Griffith … (2012)
              Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P = 0.43). Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC. © 2012 Blackwell Publishing Ltd.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Rare Tumors
                Journal ID (publisher-id): RT
                Title: Rare Tumors
                Publisher: PAGEPress Publications, Pavia, Italy
                ISSN (Print): 2036-3605
                ISSN (Electronic): 2036-3613
                Publication date (Electronic): 03 October 2017
                Publication date Collection: 03 October 2017
                Volume: 9
                Issue: 3
                Electronic Location Identifier: 7162
                Affiliations
                [1 ] Department of Oral- and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München
                [2 ] Department of Otolaryngology, Klinikum rechts der Isar der Technischen Universität München
                [3 ] Institute of Pathology, Erlangen University
                [4 ] Department of Otolaryngology, Luebeck University Hospital
                [5 ] Department of Pathology, University Medical Center Schleswig- Holstein , Campus Luebeck and Research Center Borstel
                [6 ] Leibniz Center for Medicine and Biosciences
                [7 ] Institute of Pathology, Technische Universität München, Germany
                Author notes
                Institute of Pathology, Technical University Munich, Trogerstraße 18, 81675 München, Germany. +49.8941.404166 - +49.8941.406160. carolin.mogler@ 123456tum.de

                Contributions: OB and CG contributed equally.

                Conflict of interest: the authors declare no potential conflict of interest.

                Article
                DOI: 10.4081/rt.2017.7162
                PMC ID: 5643951
                PubMed ID: 29081930
                SO-VID: 49ea5b29-7139-4f84-9039-0e5b0fd2ec61
                Copyright © ©Copyright O. Bissinger et al., 2017
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 March 2017
                Date revision received : 27 July 2017
                Date accepted : 17 August 2017
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 41, Pages: 4
                Categories
                Subject: Article

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mammary analogue secretory carcinoma,salivary gland carcinomas,mammaglobin,etv-6
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mammary analogue secretory carcinoma, salivary gland carcinomas, mammaglobin, etv-6

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