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.

Cytogenetic and immunohistochemical characterization of mammary analogue secretory carcinoma of salivary glands

“…S100 staining was seen in 11/31 ACCs but appeared much weaker and restricted compared to MASCs. This is in agreement with previous reports showing that diffuse and strong S100 expression may distinguish MASCs from ACCs [1,7]. Mammaglobin and S100 have also been suggested as proxy markers for MASC [22].…”

“…In agreement with existing knowledge, there was an almost equal gender distribution for MASC between males (n=6) and females (n= 5) [1,4,26,27]. A recent systematic review reports a slight male predominance for MASC (55%) and an average age of 44.2 years (range 14-77) [2].…”

“…A distinct subset of ACC resembling SCB was first reported in 2002 lacking the usual zymogen granules and containing bubbly eosinophilic material in variably sized cystic spaces [3]. This 'granule-poor' variant was established as MASC in 2010 when it was shown that it not only resembles SCB histologically but also harbours the same chromosomal translocation [1,17].…”

“…Mammary analogue secretory carcinoma (MASC) was first described in 2010 as a distinct salivary gland neoplasm, showing close resemblance to secretory carcinoma of the breast (SCB) [1,2]. As well as the histological similarity with SCB, MASC was also shown to harbour the t(12;15) (p13;q25) translocation and the resulting ETV6-NTRK3 fusion gene [1,3,4,].…”

“…Out of the 172 MASC cases reported in the literature until early 2015, only seven patients died from disease. In two patients death followed distant metastases, one had multiple locoregional recurrences, and one followed unspecified recurrence [1,4,27]. The remaining three involved the parotid gland showing high-grade transformation with an aggressive clinical behaviour [37].…”