Ancillary Studies for Salivary Gland Cytology
Precise cytological classification of salivary gland tumors based on cytomorphology alone is possible for many commonly encountered lesions; however, there are challenges for the cytologic diagnosis of some uncommon entities due to their cytomorphological overlap. Although not necessary or feasible for many salivary gland tumors, ancillary studies can greatly enhance accurate FNA classification using the MSRSGC and allow for the definitive diagnosis of salivary gland neoplasms when there is sufficient material. Ancillary studies may also resolve diagnostic uncertainty for FNAs that may otherwise be classified as SUMP or Suspicious for Malignancy in the MSRSGC, helping to triage patients appropriately for clinical management. A large subset of salivary gland tumors has now been characterized cytogenetically by the presence of specific molecular/genetic alterations that can be used as diagnostic markers in salivary gland FNA. These specific molecular/genetic alterations can be identified by fluorescence in situ hybridization (FISH) or high-throughput sequencing methods (i.e., next-generation sequencing). Furthermore, immunochemistry now has significant diagnostic applications in salivary gland cytology, and several new antibodies are available to identify protein surrogates of specific genetic translocations, such as MYB expression secondary to MYB:: NFIB fusion in adenoid cystic carcinoma, pan-TRK expression secondary to ETV6:: NTRK fusion in secretory carcinoma, or NR4A3 expression secondary to NR4A3 upregulation in acinic cell carcinoma. This chapter addresses the application of diagnostic immunochemical and molecular tests in salivary gland cytology.