Unlocking the Hidden: Advancing Imaging Techniques in Diagnosing Cancers of Unknown Primary in the Head and Neck Region

A cancer of unknown primary site of origin (CUP) is a definition for neoplasms whose first—and unique—presentation is of a neck mass. The urgent need to identify and characterize the primary tumor imposes a precise, prompt, and individualized diagnostic pathway to best guide the treatment. For the aim of this work, 5323 patients were identified from case series ranging from the year 2016 to 2023, selecting, from the 605 total cases in 2019, the clinical cases that met the characteristics of a CUP, which concerned 28 individuals. The 5-year follow-up of the 28 patients examined in 2019 revealed that, in more than half of the patients, the site of onset of primary tumors could not be revealed. Of these, 9 patients were classified as being affected by a CUP, and 9 patients died of carcinoma of uncertain origin; in the remaining 10 patients, the investigations were able to reveal the primary tumor. The lack of identification of a primary tumor prevents the patient from being treated with a curative intent. The identification of the primary tumor is achieved through a pathway of investigations that involves several approaches from a multidisciplinary perspective. The contribution of imaging and its increasingly important role, along with the implementation of its techniques and technologies, help make certain diagnoses in less time.