Biomarkers in Carcinoma of Unknown Primary

Current and emerging biomarkers in primary head and neck carcinoma have diagnostic, prognostic, and predictive value. Following histomorphological evaluation, immunohistochemical markers, and molecular methods may help to differentiate between numerous tumor types. Phenotypic markers which are related with squamous and neuroendocrine differentiation or viral infections are helpful in upper aerodigestive tract carcinomas. Additionally, recently described molecular alterations, such as NUT translocation or SMARCB1 and IDH2 mutations, aid in classifying them better. The prognostic importance of high-risk human papillomavirus positivity which is prominent in the oropharynx and is possible in some other sites in head and neck and the diagnostic utility of the detection of latent Epstein-Barr virus infection in nasopharyngeal carcinoma or lymphoepithelial carcinoma is notified. Immunohistochemical markers together with certain molecular alterations, especially specific translocations in salivary glands, are helpful for overcoming diagnostic difficulties and for increasingly guiding the utilization of targeted therapies. Hereby, this chapter reviews the latest developments in biomarkers in primary head and neck carcinomas with a focus on distinctive phenotypic and molecular aspects.