Clinicopathological characterization and autopsybased classification of the Cancer of Unknown Primary origin (CUP) syndrome

: Cancer of Unknown Primary origin (CUP) is characterized by metastatic tumor spread without identifiable primary tumor. CUP cohort was selected from 6966 autopsy cases (2001-2014). Type-1 ("clinical") CUPs: primary site was not found clinically but identified by autopsy. Type-2 ("clinicopathological") CUPs: no primary site either clinically or by autopsy. Type-3 ("pathological") CUPs: no tumor was suspected clinically whereas autopsy revealed metastatic spread from unidentifiable source. 2160 malignant tumors were found including 80 CUPs (type-1/2/3: 42/29/9). Cumulative incidence declined with time (3.70%; 2001-2007: 4.51%; 2008-2014: 3.19%) due to decreasing incidence of type-1 and -3 CUPs. CUPs were mostly adenocarcinomas and type-1 CUPs usually originate from the lung or pancreas. As a conclusion, type-2 and -3 CUPs may originate from microscopic-sized metastasizing primary tumors. Based on the above classification, improvement of clinical diagnostics may contribute to decreased incidence of type-1 CUPs and transfer of type-3 CUPs into type-2 category.