Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement

Abstract

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

Fig. 1

Histopathological features of MASC: a the tumour is well circumscribed and surrounded by a thick, not interrupted fibrous capsule (H&E; ×40); b microcystic and slightly dilated glandular spaces filled with an eosinophilic homogenous secretory material (H&E; ×100); c minor component is represented by papillary structures (H&E; ×100); d a macrocystic growth pattern (H&E; ×100); e cystic structures lined mostly by a single and, focally, a double layer of cells with focal apocrine differentiation (H&E; ×200); f cells with abundant pale pink vacuolated and foamy cytoplasm and vesicular, bland looking nuclei with prominent nucleoli (H&E; ×200); g a diffuse and strong staining for S100 and h mammaglobin (×100)

Fig. 2

MASC with high-grade (HG) transformation: a The tumour contains two distinct carcinomatous components. One represents conventional MASC composed of uniform neoplastic cells arranged in solid, tubular and microcystic growth structures divided by fibrous septa that were partly hyalinized. The tumour cells show typical low-grade morphology: vesicular round to oval nuclei with finely granular chromatin and distinct centrally located nucleoli (left). The HG component is composed of anaplastic cells with abundant cytoplasm and large pleomorphic nuclei (right) (H&E; ×40); b solid tumour islands of MASC high-grade component with areas of large geographical comedo-like necrosis (H&E; ×200)

Fig. 3

a Fluorescent in situ hybridization with ETV6 (12p13) break apart probe. Nuclei with split red and green signals indicate ETV6 break. Chromosomes with normal ETV6 gene show yellow signal (overlapping green and red); b expression of the ETV6-NTRK3 fusion transcript by reverse transcription PCR; c sequence analysis of the ETV6-NTRK3 fusion transcript. Arrows indicate translocation break point