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Mammary Analogue Secretory Carcinoma of Salivary Glands With High-grade Transformation: Report of 3 Cases With the ETV6-NTRK3 Gene Fusion and Analysis of TP53, β-Catenin, EGFR, and CCND1 Genes

Skálová, Alena MD, PhD*,†; Vanecek, Tomas PhD; Majewska, Hanna MD, PhD§; Laco, Jan MD, PhD; Grossmann, Petr PhD; Simpson, Roderick H. W. MB, ChB, FRCPath; Hauer, Lukas MD#; Andrle, Pavel MD#; Hosticka, Lubor MD#; Branžovský, Jindrich MD*; Michal, Michal MD*

The American Journal of Surgical Pathology: January 2014 - Volume 38 - Issue 1 - p 23–33
doi: 10.1097/PAS.0000000000000088
Original Articles

Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.

*Department of Pathology, Faculty of Medicine in Plzen, Charles University in Prague

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Bioptic Laboratory Ltd, Molecular Pathology Laboratory

#Department of Maxillofacial Surgery, Faculty of Medicine, Clinic of Dentistry, Plzen

The Fingerland Department of Pathology, Faculty of Medicine and University Hospital, Charles University in Prague, Hradec Kralove, Czech Republic

§Department of Pathology, Medical University of Gdansk, Poland

Department of Anatomical Pathology, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada

Conflicts of Interest and Source of Funding: Supported by Grant Nr. NT13701-4/2012 of IGA MH CR (Internal Grant Agency of Health Ministry, Czech Republic). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Alena Skálová, MD, PhD, Sikl’s Department of Pathology, Medical Faculty of Charles University, Faculty Hospital, E. Benese 13, 305 99 Plzen, Czech Republic (e-mail: skalova@fnplzen.cz).

© 2014 by Lippincott Williams & Wilkins.