Characterization of mammary analogue secretory carcinoma of the salivary gland: discrimination from its mimics by the presence of the ETV6-NTRK3 translocation and novel surrogate markers

Hum Pathol. 2015 Jan;46(1):94-103. doi: 10.1016/j.humpath.2014.09.012. Epub 2014 Oct 7.


Mammary analogue secretory carcinoma (MASC) is a recently recognized salivary gland tumor harboring an ETV6-NTRK3 translocation similar to secretory carcinoma of the breast. Histologically, MASC mimics papillary-cystic, microcystic, and follicular-type acinic cell carcinoma (AciCC) and low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland. Using histology, immunohistochemistry (IHC), and molecular genetic techniques, we reevaluated 18 cases originally diagnosed as AciCC between 1993 and 2012. The last of these methods was used to detect the ETV6-NTRK3 translocation. The results reconfirmed 6 cases as AciCC (3 men; average age, 63 years) and helped us reclassify 10 cases as MASC (6 men; mean age, 46 years) and 2 as LGCCC (2 women; mean age, 48 years). Using IHC, we identified the 3 histologic types according to the expression patterns of vimentin, high-molecular-weight cytokeratin, cytokeratin 19, S-100, mammaglobin, MUC1, GATA-binding protein 3, adipophilin, α-amylase, DOG-1, SOX-10, and p63. The number of tumors diagnosed as MASC indicates that AciCC includes bona fide MASC cases. Because differential diagnosis among zymogen granule-poor AciCC, MASC, and LGCCC tumors is challenging, we recommend using molecular genetic tests for ETV6-NTRK3 for accurate diagnosis. Furthermore, detailed analyses of hematoxylin and eosin-stained tissues and IHC studies using the markers described here should be incorporated into routine practices.

Keywords: Acinic cell carcinoma; Cystadenocarcinoma; ETV6-NTRK3; Immunohistochemistry; Mammary analogue secretory carcinoma; Salivary gland.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / chemistry
  • Carcinoma / classification
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma, Acinar Cell / chemistry
  • Carcinoma, Acinar Cell / classification
  • Carcinoma, Acinar Cell / genetics*
  • Carcinoma, Acinar Cell / pathology
  • Diagnosis, Differential
  • Diagnostic Errors / prevention & control
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Gland Neoplasms / chemistry
  • Salivary Gland Neoplasms / classification
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology
  • Sequence Analysis, DNA
  • Translocation, Genetic*
  • Young Adult


  • Biomarkers, Tumor
  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion

Supplementary concepts

  • Secretory breast carcinoma