Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study

Abstract

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off

“…Notably, multiple authors have described some patterns found in MASC as appearing similar to thyroid colloid-like deposition or a follicular pattern of thyroid carcinoma [1,3,7,17]. Nuclear features of our patient's tumor also resembled closely those of PTC in that the nuclei were vesicular with numerous nuclear grooves.…”

“…Recently, one case of mammary analog secretory carcinoma has been reported as arising in (or near) the thyroid gland [7]. Our report details a second patient with mammary analog secretory carcinoma apparently arising in the thyroid with diagnosis confirmed on PCR for an ETV6-NTRK3 fusion and with characteristic immunohistochemical features.…”

“…Possibly, NTRK fusion positve ''papillary thyroid carcinomas'', whether immunophenotypically PTC or immunophenotypically MASC, may be better treated by a specific targeted therapy, especially in aggressively behaving and/or high stage cases. For example, entrectinib (RXDS-101) and LOXO-101 are two new orally delivered tyrosine kinase inhibitors Stevens and colleagues reported in 2015 one patient with MASC in which the tumor appeared to infiltrate the thyroid and perilaryngeal soft tissue and which was hypothesized to have possibly arisen in ectopic minor salivary gland tissue [7]. The patient's tumor was confirmed as MASC by ETV6 translocation identified on fluorescence in situ hybridization.…”

“…The specific fusion breakpoints were not reported. It co-expressed mammaglobin and S-100 protein and was negative for TTF-1 and thyroglobulin [7].…”

“…Mammary analog secretory carcinoma expresses mammaglobin, GATA3 and variably expresses gross cystic disease fluid protein-15 (GCDFP-15) similarly to many primary breast carcinomas. Other antigens expressed include S-100 protein (diffuse in most cases), vimentin and high molecular weight keratins with variable expression reported for p63 [1,[3][4][5][6][7]. In their original description of MASC, Skalova and colleagues found an ETV6-NTRK3 fusion in all cases [1].…”