Searching for Mammary Analog Secretory Carcinoma of Salivary Gland Among Its Mimics

Andre Pinto; Vania Nosé; Claudia Rojas; Yao-Shan Fan; Carmen Gomez-Fernandez


Mod Pathol. 2014;27(1):30-37. 

In This Article

Abstract and Introduction


Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.


Mammary analog secretory carcinoma of the salivary gland is a recently described tumor with unique characteristics. The first description of mammary analog secretory carcinoma reported by Skalova et al[1] in 2010 included 16 cases of this new entity that shares morphologic and genetic characteristics with its mammary counterpart, including the ETV6-NTRK3 fusion product previously described in secretory carcinomas of the breast. The authors selected their cases among salivary gland neoplasms that morphologically resemble secretory carcinomas of the breast; ie, well-circumscribed nodules of neoplastic epithelial cells arranged in solid, microcystic, and tubular growth patterns associated with intraluminal secretions. Cytologically, the cells are bland, have vesicular nuclei and abundant pale-pink granular or vacuolated cytoplasm.[1,2]

Following the initial publication describing mammary analog secretory carcinoma, other investigators began to look back at their own institutional cases in order to reanalyze some of their salivary gland tumors. Acinic cell carcinomas, adenocarcinomas, not otherwise specified (NOS), polymorphous low-grade adenocarcinomas, mucoepidermoid carcinomas, and cystadenocarcinomas are examples of cases re-evaluated in a small number of recently published studies, describing additional cases of mammary analog secretory carcinoma. Most cases of mammary analog secretory carcinoma had been initially classified as acinic cell carcinomas.[3–7]

Immunohistochemistry studies may be useful in the differential diagnosis between mammary analog secretary carcinoma and its mimics. The former are reactive for S-100 protein and mammaglobin in the vast majority of cases,[1,3–6,8] however, these two markers, S-100 in particular, are likewise found to be occasionally positive in other adenocarcinomas of salivary gland origin. Acinic cell carcinomas tend to be negative for mammaglobin, but can rarely demonstrate immunoreactivity for S-100. ANO1 (also known as DOG1), initially described in gastrointestinal stromal tumors, is a marker of salivary acinar and intercalated duct differentiation. A recent study by Chenevert et al, described the positive immunohistochemical expression of the ANO1 protein in all of their cases of acinic cell carcinomas, whereas the mammary analog secretory carcinomas were largely negative for this marker.[9]

Molecularly, mammary analog secretory carcinomas, like their breast counterpart, harbor a balanced translocation t(12;15)(p13;q25), which creates an ETV6-NTRK3 fusion gene.[1] This same genetic aberration is also seen in cellular mesoblastic nephroma,[10] congenital fibrosarcoma,[11] and in some hematologic malignancies,[12,13] but has not been described in other neoplasms of the salivary gland.

The aim of this study is to reanalyze our own database of salivary gland cases for the presence of mammary analog secretory carcinoma using the recently described morphologic criteria, together with immunohistochemistry for mammaglobin, S-100, and DOG1 and fluorescent in situ hybridization (FISH) analyses for ETV6-NTRK3 translocation product.