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A Photo Essay -  Mammary Analogue Secretory Carcinoma of Salivary Glands (MASC): 

A recently described Salivary Gland Tumour -

 

Dr Sampurna Roy MD                       

 

Mammary Analogue Secretory Carcinoma of Salivary Glands (MASC): 

This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast.

Secretary Carcinoma of the breast

 

Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumours.

Key Histological features:

-Cystic, tubular, solid and/or papillary architecture

-Eosinophlic vacuolated cytoplasm

-Intraluminal and/or intracellular colloid-like secretions that stain positive for periodic acid Schiff (PAS) and are diastase-resistant  

-Low-grade, bland and pale nuclei

-Positive staining for S-100

-Positive staining for mammaglobin, a uteroglobin protein identified in breast tissue, endometrial cancer and sweat gland carcinomas

Mammary Analogue Secretory Carcinoma of Salivary Gland Origin: An Update and Expanded Morphologic and Immunohistochemical Spectrum of Recently Described Entity.

 

a) The tumour is well circumscribed and surrounded by a thick, not interrupted fibrous capsule  ;

b) Microcystic and slightly dilated glandular spaces filled with an eosinophilic homogenous secretory material ;

c) Minor component is represented by papillary structures  ;

d) A macrocystic growth pattern  ;

e) cystic structures lined mostly by a single and, focally, a double layer of cells with focal apocrine differentiation  ;

f ) cells with abundant pale pink vacuolated and foamy cytoplasm and vesicular, bland looking nuclei with prominent nucleoli  ;

Majewska H, Skálová A, Stodulski D, et al. Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement. Virchows Archiv. 2015;466(3):245-254. doi:10.1007/s00428-014-1701-8.  (This article is distributed under the terms of the Creative Commons Attribution License)

Mammary analogue secretory carcinoma of salivary glands (MASC) was first described by Skálová et al. in 2010.

This rare salivary gland tumour is characterized by the ETV6-NTRK3 fusion gene.

It is usually seen in men and predominantly involves parotid gland. Mammary analogue secretory carcinoma can occur in other locations like lips.

More image: Macroscopic and histological morphology of mammary analogue secretory carcinoma. The cut section of the tumor was uncircumscribed and whitish, invading into the connective tissue surrounding the parotid gland

Microscopically, this low grade tumour has a lobulated appearance and displays   microcystic, cystic-papillary, glandular, and solid patterns. The glandular spaces contain  abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff, mucicarmine, MUC1, MUC4, and mammaglobin. The neoplastic cells have pale, ovoid nuclei with minimal pleomorphism, the cytoplasm is vacuolated or eosinophilic.  Image1 ; Image2 ; Image3 ; Image4

Macrocystic pattern    

 

Intraluminal and intracytoplasmic PAS-D positive secretion

Serrano-Arévalo ML, Mosqueda-Taylor A, Domínguez-Malagón H, Michal M. Mammary Analogue Secretory Carcinoma (MASC) of salivary gland in four Mexican patients. Medicina Oral, Patología Oral y Cirugía Bucal. 2015;20(1):e23-e29. doi:10.4317/medoral.19874.  (This is an open-access article distributed under the terms of the Creative Commons Attribution License)

Cytomorphology of mammary analogue secretory carcinoma.

Images

The cytological distinction between zymogen granule-poor Acinic cell carcinoma and MASC without molecular study or immunohistochemical study is very difficult, since the cytology of MASC has many overlapping features with Acinic cell carcinoma. However, there are several cytological features suggestive of MASC, such as papillary structure, extracellular and intracellular mucinous material, vacuolated cytoplasm, tumour cells with low-grade nuclear atypia, and abundant vascularity.

Immunohistochemistry: 

The tumor cells are strongly positive for S100 protein, STAT5a and mammaglobin and negative for DOG-1. STAT5a shows strong nuclear expression in tumor cells.  Mammaglobin in all cases stains cytoplasm.

S100 protein

Image       STAT5a

Image   Mammaglobin

Perineural invasion is rare and lymphovascular invasion has not been reported. MASC is currently regarded as a low-grade carcinoma.

MASC has a higher risk for regional lymph node involvement than acinic cell carcinoma.

Image  Lymph node metastasis of MASC.

Mammary analogue secretory carcinoma of salivary glands may follow an aggressive behavior or transform into a high grade neoplasm. Skalova reported cases with conventional MASC and a population of anaplastic cells with perineural invasion.  

Differential diagnosis include:

(i) Mucoepidermoid carcinoma (MEC):  Low-grade mucoepidermoid carcinoma consists of various cell types ( it may contain variable proportions of squamous cells, clear cells, mucocytes, oncocytes, intermediate cells, and columnar cells). MASC typically lacks p63 staining and shows diffuse S100 positivity in most cases, which would be unusual in MEC, as would papillary formations and hobnailing in the lining of the cysts. 50 % of MEC are characterized by a t(11; 19) translocation coding for a CRTC1-MAML2 fusion protein.

(ii) Low Grade Cribriform Cystadenocarcinoma (Low Grade Salivary Duct Carcinoma) : Cystadenocarcinoma may resemble cribriform ductal carcinoma in situ (DCIS) not observed in Mammary analogue secretory carcinoma. Low grade cribriform cystadenocarcinoma (LGCC) must be considered in differential diagnosis of MASC as well. Although LGCC shares with MASC strong diffuse S-100 protein expression, LGCC shows a complete intact myoepithelial rim around tumor nests which is not a feature of MASC 

(iii) Acinic cell carcinoma presents acinic cells, intercalated duct cells or clear cells, and their cytoplasm is rich in zymogen granules.The large serous acinar cells with cytoplasmic PAS-positive zymogen-like granules, typical of Acinic cell carcinoma, are completely absent from MASC.  The granule-poor variant of Acinic cell carcinoma is difficult to differentiate from Mammary analogue secretory carcinoma. It is negative for S-100 protein, STAT5a and mammaglobin, and positive for transferrin, lactoferrin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, carcinoembryonic antigen, and Leu M1 antigen. ETV6-NTRK3 gene rearragement present in MASC is not seen in salivary acinic cell carcinoma.

 

 

Reference:

Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.

Serrano-Arévalo ML, Mosqueda-Taylor A, Domínguez-Malagón H, Michal M. Mammary Analogue Secretory Carcinoma (MASC) of salivary gland in four Mexican patients. Medicina Oral, Patología Oral y Cirugía Bucal. 2015;20(1):e23-e29. doi:10.4317/medoral.19874.

Mammary Analogue Secretory Carcinoma of Salivary Gland Origin: An Update and Expanded Morphologic and Immunohistochemical Spectrum of Recently Described Entity.

Majewska H, Skálová A, Stodulski D, et al. Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement. Virchows Archiv. 2015;466(3):245-254. doi:10.1007/s00428-014-1701-8.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

 

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