J Cancer 2020; 11(13):3919-3931. doi:10.7150/jca.42880 This issue


Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

Alaa T. Alshareeda1✉, Batla S. Al-Sowayan1, Reem R. Alkharji2, Sahar M. Aldosari3, Abdullah M. Al subayyil1, Ayidah Alghuwainem1

1. Stem Cells and Regenerative Medicine Unit, Cell Therapy & Cancer Research Department, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia
2. Research Department, Health Sciences Research Centre, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
3. Cytogenetic and Molecular Genetics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Alshareeda AT, Al-Sowayan BS, Alkharji RR, Aldosari SM, Al subayyil AM, Alghuwainem A. Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?. J Cancer 2020; 11(13):3919-3931. doi:10.7150/jca.42880. Available from https://www.jcancer.org/v11p3919.htm

File import instruction


Metastasis is a late event in the progression of any tumour. However, invasive cancers are occasionally detected in the form of metastatic lesions without a clearly detectable primary tumour. Cancer of unknown primary site (CUP) is defined as a confirmed metastatic tumour, with unknown primary tumour site, despite the standardized diagnostic approach that includes clinical history, routine laboratory tests, and complete physical examination. Due to the lack of basic research on its primary causes, CUP is appropriately termed an 'orphan' cancer. Nevertheless, CUP accounts for 2-5% of diagnosed malignancies. To date, it is unclear whether CUP is an entity with primary dormancy as its hallmark or an entity with genetic abnormalities that cause it to manifest as a primary metastatic disease. In this review, we discuss different aspects of CUP, including its current diagnostic methods, angiogenesis effectors, relationship with cancer stem cells and current treatments.

Keywords: Cancer of unknown primary, Immunohistochemistry, Genetic abnormality, Cancer Stem Cells, and angiogenesis