Mammary Analogue Secretory Carcinoma of Salivary Glands With High-grade Transformation

Abstract

Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

“…For acinic cell carcinoma with HGT a side by side comparison with conventional acinic cell carcinoma confirms a more aggressive behavior even when corrected for age. Secretory carcinoma and PAC have also been reported to rarely undergo high-grade transformation, which was part of the impetus to drop the term "low-grade" from PAC [9,41].…”

“…Secretory carcinoma is typically indolent like acinic cell carcinoma, but may show a slightly higher lymph node metastatic rate (up to 25%) than true acinic cell carcinoma [8]. Prognostic features include stage and high-grade transformation (see below) [9]. With the expansion of selective TRK inhibitors, recognition of advanced stage cases of secretory carcinoma may eventually have direct therapeutic relevance [10].…”

Mammary analogue secretory carcinoma: A rare salivary gland tumour

“…Both tumours consist of microcystic and solid areas with abundant vacuolated colloid-like PAS-positive secretions within the microcystic spaces. [6,7] Both tumours are triple (ER/PR/Her-2)-negative. Breast secretory carcinomas are clinically slow growing, recur locally, occur mainly in young females and generally have a favourable outcome.…”

“…[12,19] MASC is considered to be a low-grade carcinoma that is slowgrowing, painless and with a relatively favourable prognosis. [7,12] It does not usually infiltrate surrounding structures, and perineural and vascular invasion is unusual. [12] MASCs have a 15% risk of local recurrences, especially if incompletely excised.…”

“…This ETV6-NTRK3 gene encodes for a chimeric tyrosine kinase. [3,4,7,15] Secretory carcinoma of the breast also has a recurrent chromosomal translocation t(12;15) (p13;q25), which also occurs some cases of myelogenous leukaemia, infantile fibrosarcoma and congenital mesoblastic nephroma. [12] Currently, salivary MASC is the only salivary gland tumour to harbour the recurrent chromosomal translocation t(12;15) (p13;q25).…”