Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.
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.
Skálová
Alena
A
Department of Pathology, Charles University, Pilsen, Czech Republic. skalova@fnplzen.cz
Vanecek
Tomas
T
Sima
Radek
R
Laco
Jan
J
Weinreb
Ilan
I
Perez-Ordonez
Bayardo
B
Starek
Ivo
I
Geierova
Marie
M
Simpson
Roderrick H W
RH
Passador-Santos
Fabricio
F
Ryska
Ales
A
Leivo
Ilmo
I
Kinkor
Zdenek
Z
Michal
Michal
M
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
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