Parotid Gland, Secretory carcinoma

Secretory carcinoma, previously known as mammary analogue secretory carcinoma (MASC), is a newly recognized entity amongst salivary gland malignancies. Like its counterpart occurring in the breast, secretory carcinoma often harbours the characteristic chromosomal translocation t(12;15)(p13,q25) that results in an ETV6-NTRK3 gene fusion. Before it was recognized as a distinct entity, secretory carcinoma was often diagnosed as an acinic cell carcinoma or adenocarcinoma, NOS.

Although secretory carcinomas often show architectural overlap with acinic cell carcinomas (i.e. microcystic, follicular and solid patterns), there are several histologic, immunohistochemical and molecular features that help distinguish these two entities from one another. Secretory carcinomas cells lack the basophilic, cytoplasmic zymogen granules characteristic of acinic cell carcinomas. Instead, the tumour cells usually have lightly eosinophilic, vacuolated or flocculent cytoplasm. Atypia is usually mild, with tumour cells showing round/oval vesicular nuclei and small, central nucleoli. PAS/D+ eosinophilic secretions are often present within microcystic and tubular spaces.

In terms of immunohistochemical markers, secretory carcinomas usually show positive staining for pan-cytokeratin, S100, mammaglobin and GCDFP-15. Conversely, acinic cell carcinomas are typically strongly DOG1+ and S100-. Although the combination of histology and immunohistochemistry can often lead to an accurate diagnosis of this neoplasm, molecular testing for ETV6 gene rearrangement can be utilized for confirmation. Interestingly, the case of a high-grade secretory carcinoma was recently reported with an ETV6-MET gene fusion, demonstrating that a subset of secretory carcinomas exhibit alternative ETV6 fusion partners.

Clinically, secretory carcinomas exhibit a slight male predominance and often occur in the parotid gland or oral cavity. This is in contrast to acinic cell carcinomas, which primarily occur in the parotid gland and rarely arise in minor salivary gland sites. Fortunately, the prognosis is generally good with most cases behaving indolently, but local recurrence and metastases are possible. Low-grade tumours are often treated by complete surgical resection.