Cancers are usually grouped by where they first started (the primary site), such as breast cancer or lung cancer. They can also be grouped by type of cell they start from. For cancer of unknown primary (CUP), there are 5 main types. 

Tests to look for the type of cancer cells

Tests can give doctors useful information about the cancer, even when a primary tumour can't be found. Doctors can get important clues about the cancer from:

• your gender
• the position of the secondary cancer
• detailed laboratory information about the cancer cells 

Laboratory tests

To find out what the type of cell is, your doctor takes a tissue sample (biopsy) and sends it to the laboratory to be looked at under a microscope. The doctor in the lab (pathologist) can look at the shape and structure of the cells.

They may also test the tissue sample using antibodies to look for tumour markers. Tumour markers are chemicals produced by some cancer cells. Some tumour markers are made by only one type of cancer, while others can be made by several different types of cancer.

The study of tumour markers is called immunohistochemistry (IHC). Tumour markers are often called IHC markers.

Types of CUP

Cancer of unknown primary (CUP) can be split into 5 main groups:

Adenocarcinoma

Adenocarcinoma starts in the gland cells. These cells line certain organs of the body, and release substances such as mucus or digestive juices. At least 60 out of 100 cancers of unknown primary (60%) are adenocarcinomas. 

The most common places for secondary cancers to be found are the lymph nodes, liver, lung and bone. 

Squamous cell carcinoma

Squamous cells are flat cells found in the skin and in the lining of parts of the body such as:

• nose
• throat
• lungs
• cervix
• anus

The secondary tumours are usually noticed as swollen (enlarged) lymph nodes in the neck or groin. Around 5 out of 100 cancers of unknown primary (5%) are squamous cell tumours. 

Neuroendocrine tumours

About 3 in 100 cancers of unknown primary (3%) are neuroendocrine tumours (NETS). Carcinoid tumours are the most common of these. They develop mainly in the small bowel or other parts of the digestive system. But they can also occur in the lung, pancreas, kidney, ovary or testicle.

Neuroendocrine tumours usually respond very well to treatment.

Poorly differentiated carcinoma

This type of cancer starts in the cells that make up the tissue that covers the outside of the body and lines the internal organs (epithelial cells). Doctors usually can't tell exactly what type of epithelial cells the cancer started in. This is because the cells look so different from normal cells.

Around 30 in 100 cancers of unknown primary (30%) are this type.

Poorly differentiated neoplasm

The cells of the tumour look so abnormal the doctor can’t tell what type of cell the cancer started in. About 5 out of 100 cancers of unknown primary (5%) are this type. But after further testing in the lab, some of these turn out to be carcinomas or other types of cancer such as lymphoma or melanoma.

Other cancer types

Occasionally cancers such as melanoma, sarcoma and germ cell tumours are diagnosed without finding the primary tumour. Doctors treat them following guidelines for these specific types of cancer, and not cancer of unknown primary.