Authors’ reply to Kaur

We thank Dr. Kaur[1] for showing interest in our review titled "Looking through the same lens – Immunohistochemistry for salivary gland tumors: A narrative review on the testing and management strategies" and for highlighting the complexities associated with the diagnosis of salivary gland malignancies, particularly in small biopsies. The points raised regarding the limitations of histomorphology, sampling errors, and the utility of immunohistochemistry (IHC) in determining tumor lineage resonates with our own experiences.[2] Furthermore, we acknowledge the evolving landscape of molecular diagnostics in salivary gland tumors, as outlined by Kaur. The incorporation of techniques such as fluorescent in situ hybridization, polymerase chain reaction, and next-generation sequencing has undoubtedly enhanced our understanding of tumor-specific gene rearrangements. We appreciate the emphasis on the importance of surrogate molecular markers, such as pleomorphic adenoma gene 1 (PLAG1), high-mobility group A2 (HMGA2), v-myb avian myeloblastosis viral oncogene homolog (MYB), and pan-tropomyosin receptor kinase (pan-TRK), in aiding diagnosis and guiding targeted therapy decisions.[3,4] However, in salivary gland malignancies, the identification of these surrogate molecular markers using IHC needs to be balanced with increased access to comprehensive genomic profiling, which provides detailed mutations, copy number variations, and other genomic changes not detectable by IHC-based protein profiling alone.[4] The inherent subjectivity with IHC adds to the difficulty in targeting possible therapeutic options, which may be protein/tumor agnostic. In addition, running multiple sequential IHC panels for the myriad of molecular markers available may lead to complication of the puzzle, rather than helping the clinician and pathologist solve it. In conclusion, we agree that while IHC serves as a valuable adjunct, its limitations, particularly regarding specificity, should be acknowledged, and results should be interpreted in conjunction with clinical and molecular findings. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.