Pearls from Your Peers | Molecular Diagnostics and Targeted Therapeutics for Salivary Gland Neoplasms

What molecular testing is necessary right now when deciding management for certain salivary gland malignancies?

For many salivary gland malignancies, histology alone may not be sufficient for accurate diagnosis and categorization. The use of additional protein, hormonal, and fusion markers is commonplace and necessary to help the pathologists. Send-out tests looking for molecular fusions, such as ETV6-NTRK3 for secretory carcinoma, Myb-NFIB for adenoid cystic carcinoma, or CRTC1-MAML2 for mucoepidermoid carcinoma, can solidify the histologic findings, particularly for dedifferentiated tumors or if there is histologic overlap. 

What does the future hold for molecular diagnostic tests for salivary gland neoplasms?

It is likely that a panel of markers will be assembled to help with the diagnosis of salivary gland tumors. This is perhaps more needed in the realm of fine needle aspiration biopsy classification, wherein the cytology can be meaningful but not absolute. A molecular panel that would incorporate many of the known markers as well as unique gene rearrangements would be helpful.

What does the current clinical trial landscape suggest for the role of targeted therapies based on molecular profiling of salivary gland malignancies?

Although the success of targeted therapies for salivary gland cancers has been limited in the past, there is increasing hope that we can capitalize on some of the unique features of salivary gland cancers. For example, the use of hormonal treatments for salivary duct carcinoma, which often express androgen, estrogen, or progesterone receptor, has shown some benefit and is being studied. The development of Trk inhibitors is also specific for recurrent or metastatic secretory carcinomas that universally express Trk-fusion proteins. 

There are many other unique molecular alterations in salivary gland cancers, such as unique gene fusions that might be important in driving these cancers. However, we have a poor understanding of what these gene rearrangements are doing and how to disrupt them; therefore, there is much work to be done before we can understand how to capitalize on these unique alterations. 

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