Ancillary testing in salivary gland cytology: A practical guide.

Salivary gland cytology is challenging, and historically the role of ancillary testing has been limited. However, numerous molecular/genetic advances in the understanding of salivary gland neoplasms during the last decade have facilitated the development of many useful diagnostic markers, such as PLAG1 and HMGA2 immunohistochemistry for pleomorphic adenoma and ETV6 fluorescence in situ hybridization for secretory carcinoma. Numerous salivary gland neoplasms are characterized by specific molecular/genetic alterations, many of which can be identified on cytologic preparations by karyotype analysis, fluorescence in situ hybridization, or immunohistochemical surrogates. Next-generation sequencing also has potential diagnostic applications, although to the authors' knowledge it currently has no routine role in salivary cytology. The primary goal of salivary fine-needle aspiration (FNA) is to facilitate appropriate clinical management. Ancillary testing has greatly enhanced the ability for accurate classification as per The Milan System for Reporting Salivary Gland Cytopathology and allows for the definitive diagnosis of many salivary FNA specimens, and also may resolve diagnostic uncertainty for FNAs that may be classified in The Milan System for Reporting Salivary Gland Cytopathology categories of salivary gland neoplasm of uncertain malignant potential or suspicious for malignancy. This review provides an updated discussion of the molecular/genetic features of the more commonly encountered salivary neoplasms by FNA, and discusses the application of available diagnostic immunohistochemical and molecular tests in salivary gland cytology.