From Biology to Diagnosis and Treatment: The Ariadne's Thread in Cancer of Unknown Primary.

Cancer of unknown primary (CUP) encloses a group of heterogeneous tumours, the primary sites for which cannot be identified at the time of diagnosis, despite extensive investigations. CUP has always posed major challenges both in its diagnosis and management, leading to the hypothesis that it is rather a distinct entity with specific genetic and phenotypic aberrations, considering the regression or dormancy of the primary tumour; the development of early, uncommon systemic metastases; and the resistance to therapy. Patients with CUP account for 1-3% of all human malignancies and can be categorised into two prognostic subsets according to their clinicopathologic characteristics at presentation.