Integrative diagnostic approach to salivary gland tumors: from clinical evaluation to molecularly targeted therapy

Diagnosing salivary gland tumors remains challenging due to their clinical and biological complexity, histopathologic diversity, and overlapping morphology. Over the last few years, molecular profiling has emerged as a key tool for improving tumor classification, shedding light on the cellular and molecular mechanisms underlying tumors pathogenesis. This review provides a comprehensive exploration of the clinical application of molecular profiling in the decision to indicate targeted therapy for salivary gland neoplasm. The increasing adoption of innovative biological markers associated with Next-Generation Sequencing highlights the potential of molecular diagnostic approaches as well as the prediction of therapeutic response. While immunohistochemistry remains a reliable and widely accessible ancillary tool for characterizing specific salivary gland tumors subtypes, additional validation using in situ hybridization, reverse transcription polymerase chain reaction or Next-Generation Sequencing may enhance diagnostic accuracy and facilitate the identification of actionable molecular alterations in the appropriate clinical and morphological context. This integrated diagnostic approach strengthens clinical decision-making and opens new avenues for precision-targeted therapy in the management of salivary gland tumors. As molecular insights continue to expand, the integration of traditional and modern tools will be critical to improving diagnostic accuracy, prognostic stratification, and treatment outcomes for patients with salivary gland tumors.