Open Access Research article

Causes of death in patients with extranodal cancer of unknown primary: searching for the primary site

Matias Riihimäki12*, Akseli Hemminki3, Kristina Sundquist24 and Kari Hemminki12

Author Affiliations

1 Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany

2 Center for Primary Health Care Research, Lund University, Malmö, Sweden

3 Cancer Gene Therapy Group, Transplantation Laboratory & Department of Pathology, Haartman Institute, University of Helsinki, Helsinki 00290, Finland

4 Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA

For all author emails, please log on.

BMC Cancer 2014, 14:439  doi:10.1186/1471-2407-14-439

Published: 14 June 2014



Cancer of unknown primary (CUP) is a fatal cancer, accounting for 3–5% of all diagnosed cancers. Finding the primary site is important for therapeutic choices and we believe that the organ which is designated as the cause of death may give clues about the primary site.


A total of 20,570 patients with CUP were identified from the Swedish Family-Cancer Database. Causes of death – as reported in the death certificate - were investigated, analyzing reported metastatic sites and histological subtypes separately. Survival was compared with metastatic cancer with a known primary tumor.


An organ-specific cancer could be identified as a cause of death in approximately 60% of all CUP patients with adenocarcinoma or undifferentiated histology. In adenocarcinoma, lung cancer was the most frequent cause of death (20%), followed by pancreatic cancer (14%), and ovarian cancer (11%). Lung cancer was the most common cause of death in patients with CUP metastases diagnosed in the nervous system (69%), respiratory system (53%), and bone (47%), whereas ovarian cancer was the most common cause of death when CUP was diagnosed in the pelvis (47%) or the peritoneum (32%). In CUP diagnosed in the liver, liver and pancreatic cancers accounted for 26% and 22% of deaths, respectively. Also in squamous cell CUP, lung cancer was the most common cause of death (45%).


According to the causes of death, the primary site appeared frequently to be either the organ where CUP metastases were diagnosed or an organ which may be traced through the known metastatic patterns of different cancer types.

Cancer of unknown primary; CUP; Cause of death