Finding and characterizing mammary analogue secretory carcinoma of the salivary gland

Abstract

Background: A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.

Methods: Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor.

Results: Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive.

Conclusions: MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

Keywords: Carcinoma, acinar cell; ETV6-NTRK3 fusion protein, human; In situ hybridization, fluorescence; Salivary gland neoplasms.

Fig. 1

ETV6 fluorescence in situ hybridization (FISH). (A) ETV6 FISH showing 1 fused (yellow) and 1 split (red and green) signal indicative of a translocation. (B) Mimic mammary analogue secretory carcinoma showing a negative ETV6 FISH as evident by 2 intact signals in each cell.

Fig. 2

Usual mammary analogue secretory carcinoma (MASC) morphologic features. (A) Gross photograph showing a lobulated and whitish-yellow colored tumor of the parotid gland. (B) MASC showing microcystic and papillary-cystic growth pattern. (C, D) Admixture of variable cell types with eosinophilic or vacuolated cytoplasm and intraluminal secretory material.

Fig. 3

Unusual histologic features of mammary analogue secretory carcinoma. (A) One prominent macrocyst with intraluminal papillary proliferation. (B) Variable-sized cysts among the fibrous stroma and mucinous metaplasia.

Fig. 4

Unusual histologic features of mammary analogue secretory carcinoma. (A) Microcystic growth pattern showing dedifferentiation with transitional area. (B) Solid growth pattern with high-grade cellular features.

Fig. 5

Four examples of histologic features of mimic mammary analogue secretory carcinoma (A and B; C and D; E; F). (A) Macrocyst with extensive papillary proliferation. (B) Papillae showing an eosinophilic but cuboidal to columnar appearance. (C) Macrocyst showing intraluminal papillary proliferation with large papillae. (D) Papillae showing clear to oncocytic cytoplasm. (E) Solid nests with clear to reticular cytoplasm surrounded by very thin fibrovascular septa. (F) Glandular growth pattern in prominent sclerosing stroma.

Fig. 6

S100 protein immunohistochemistry. (A) Mammary analogue secretory carcinoma (MASC) with strong S100 protein immunostaining. (B) Mimic MASC with strong S100 protein immunostaining.