Salivary gland neoplasms: the role of molecular testing in optimizing patient care
In this interview, Gloria H. Sura (University of Texas the MD Anderson Cancer Center, TX, USA) and Jessica S. Thomas (Weill Cornell Medical College and Houston Methodist Hospital, TX, USA) discuss the current diagnostic challenges with salivary gland neoplasms and how molecular testing can help to overcome them. They also highlight different techniques for molecular testing and how they can be integrated into routine clinical practice to improve patient outcomes.
What are the current diagnostic challenges with salivary gland neoplasms?
Salivary gland neoplasms are a relatively rare type of head and neck cancer that pose several diagnostic challenges to pathologists [1], including high histologic diversity and overlapping morphologic features that complicate diagnosis. Limited sample volume from minimally invasive sampling techniques, such as fine-needle aspiration (FNA) specimens, can also pose a challenge for downstream ancillary testing.
Furthermore, a lack of standardized molecular testing guidelines, along with the limited clinician awareness and access to molecular testing in some laboratories, can lead to inconsistencies in diagnostic approaches. Additionally, cost and insurance barriers may delay or prevent patients from receiving molecular testing.
How can molecular testing help to overcome these challenges?
Molecular testing methodologies have improved diagnostic and therapeutic approaches to salivary gland neoplasms by enhancing diagnostic accuracy and enabling targeted therapies through biomarker testing.
For diagnostic accuracy, well-characterized molecular alterations can improve FNA and small biopsy diagnostics, especially in tumors with morphologic overlap, such as MYB::NFIB fusion in adenoid cystic carcinomas or CRTC1::MAML2 fusion in mucoepidermoid carcinomas.
Molecular profiling enables more precise prognostication, helping to avoid overtreatment in low-risk cases while guiding more aggressive management for high-risk tumors. This reduces unnecessary surgical interventions by providing clearer risk stratification.
For targeted therapies, biomarker-driven classification allows for personalized treatment strategies such as NTRK inhibitors for NTRK fusion-positive tumors and androgen receptor inhibitors for AR-positive salivary duct carcinomas.
What are some of the techniques used for molecular testing, and how can they aid in diagnosing cancer and subsequent treatment?
Clinicians can use an array of ancillary testing for molecular testing, including next-generation sequencing, which detects a broad range of genetic alterations, including mutations, fusions/structural rearrangements and copy number changes. As well as fluorescence in situ hybridization, which identifies key gene fusions (e.g., MYB, NTRK, RET). Immunohistochemistry and reverse transcription PCR can also be used, which screen for biomarkers like androgen receptor or HER2 expression and confirms specific fusion transcripts with high sensitivity, respectively.
How can molecular testing enable personalized therapeutic strategies and optimize patient care?
As these tumors are frequently driven by well-documented genetic alterations, molecular testing can serve as an important tool for optimizing patient care [1]. For example, NTRK gene fusions are present in an overwhelming majority of secretory carcinomas. Clinical trials involving NTRK inhibitors, such as larotrectinib and entrectinib, have shown efficacy in patients with solid organ tumors harboring NTRK gene fusions, including salivary gland neoplasms, leading to US FDA approvals of these therapies. This also highlights the importance of molecular testing for optimizing patient care.
Androgen receptor expression is also present in most salivary duct carcinomas and patients with these tumors may benefit from androgen deprivation therapy. Trials with enzalutamide and abiraterone, drugs that target androgen receptor signaling, have shown promise in treating AR-positive salivary duct carcinomas, shifting treatment paradigms. Additionally, androgen deprivation therapy has shown to improve progression-free and overall survival in these patients.
HER2 expression can also be seen in salivary gland neoplasms, although there is no established consensus for treating HER2 positivity in these tumors, patients have benefited from treatment protocols, similar to those used for breast cancer [1]. Trastuzumab and afatinib are now being investigated for HER2-positive salivary gland tumors, following these protocols.
The use of potential targeted therapies is also under investigation for patients with salivary gland neoplasms harboring RET gene fusions, mutations in PIK3CA and BRAF genes. Preliminary results look promising.
How would you like to see molecular testing integrated into routine clinical practice?
Although salivary gland neoplasms are rare and heterogeneous, the molecular characterization of them is imperative, given their limited treatment options [1]. Some ways in which molecular testing could be integrated into routine clinical practice is by encouraging FNA sample acquisition and preparation with molecular testing, thereby improving tissue stewardship. Additionally, awareness of molecular testing could be increased through CME courses, workshops and interdisciplinary collaboration.
To further help with integration, medical societies should establish clear molecular testing protocols for salivary gland tumors, with molecular testing being made accessible and reimbursed to prevent financial barriers. By integrating molecular testing into routine practice, clinicians can achieve more precise diagnoses, personalized treatment strategies and improved outcomes for patients with salivary gland malignancies.
Interviewee profiles:
Dr. Gloria H. Sura is board-certified in Anatomic and Clinical Pathology, Cytopathology, and Molecular Genetic Pathology. She serves as an Assistant Professor at The University of Texas MD Anderson Cancer Center, specializing in cytopathology and molecular diagnostics. Her research focuses on preanalytical variables in molecular testing, biomarker optimization, and personalized oncology. She completed her residency training in Anatomic and Clinical Pathology at Louisiana State University Health Sciences Center New Orleans (LA, USA) followed by fellowship training in Cytopathology and Molecular Genetic Pathology at Houston Methodist Hospital in the Texas Medical Center (USA).
Dr. Jessica S. Thomas is board-certified in Clinical Pathology and Molecular Genetic Pathology. She is an assistant professor at Weill Cornell Medical College (NY, USA) and Houston Methodist Hospital (TX, USA), where she serves as co-medical director of the Molecular Diagnostic Pathology Laboratory and leads the Diagnostic Molecular Oncology team. She also directs the Molecular Genetic Pathology fellowship and oversees Clinical Pathology and Laboratory Science training programs. Dr. Thomas earned her MPH from the University of Southern Mississippi (MS, USA) and her MD and PhD from LSU Health Sciences Center (LA, USA). She completed her pathology residency and molecular genetic pathology fellowship at Vanderbilt University (TN, USA). A fellow of the College of American Pathologists and a member of its Personalized Healthcare Committee, her work focuses on molecular diagnostics, assay development, and trainee education in molecular pathology, clinical pathology, and lab management.
The opinions expressed in this interview are those of the author and do not necessarily reflect the views of Oncology Central or Taylor & Francis Group.