title: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.
abstract: 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.
authors.affiliation: Department of Pathology, Charles University, Pilsen, Czech Republic. skalova@fnplzen.cz
authors.forename: Alena
authors.initials: A
authors.lastname: Skálová
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Radek
authors.initials: R
authors.lastname: Sima
authors.forename: Jan
authors.initials: J
authors.lastname: Laco
authors.forename: Ilan
authors.initials: I
authors.lastname: Weinreb
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Ivo
authors.initials: I
authors.lastname: Starek
authors.forename: Marie
authors.initials: M
authors.lastname: Geierova
authors.forename: Roderrick H W
authors.initials: RH
authors.lastname: Simpson
authors.forename: Fabricio
authors.initials: F
authors.lastname: Passador-Santos
authors.forename: Ales
authors.initials: A
authors.lastname: Ryska
authors.forename: Ilmo
authors.initials: I
authors.lastname: Leivo
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kinkor
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D003131:Combined Modality Therapy; D003536:Cystadenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012469:Salivary Glands / Q000601:surgery; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein