Types of cancer of unknown primary (CUP)

Even when a primary tumour cannot be found, better diagnostic tests may now give much more information about it. Your gender, the position of the secondary cancer in the body, and detailed laboratory information about the tumour cells, are important clues in your diagnosis. The type of cancer that you have depends on the types of cell it has developed from. To find this out, your doctor will take a tissue sample (biopsy) and send it to a laboratory where a pathologist will examine it closely.

The tumour cells may look very abnormal under a microscope. The term for this is poorly differentiated or undifferentiated. This means that it may not be possible to tell what type of cancer it is just by looking at the shape and structure of the cells.

The pathologist may also test the tissue sample using antibodies to find tumour markers. Tumour markers are chemicals produced by cancer cells. Some tumour markers are produced by one type of cancer, while others can be made by several different types of cancer. The study of tumour markers is called immunohistochemistry (IHC) and tumour markers are often called IHC markers.

In 1 in 20 (5%) of all melanoma cases the primary tumour cannot be found. When a biopsy of the secondary tumour shows that it is melanoma it is called a melanoma of unknown primary (MUP). It is then treated as stage 3 or 4 melanoma.

Some lymphoma cells can look like other types of cancer. Lymphoma can sometimes be mistaken for secondary cancer in the lymph nodes and is classed as UPC. Tumour markers can help to make a diagnosis of lymphoma. This means that lymphoma is the primary cancer and it is treated as any other lymphoma of a similar type and stage. Very rarely a mass of leukaemia cells can also look similar to other cancers.

Most cancers of unknown primary (CUP) are carcinomas.  They are subdivided into

• Germ cell tumours
• Squamous cell tumours
• Neuroendocrine tumours
• Adenocarcinoma
• Carcinoma of solid tumours

Germ cell tumours

Germ cell tumours develop from cells that become sperm or eggs. Almost all of them are either seminoma or teratoma of the testicle. Germ cell tumours occur very rarely in women. 1 or 2% of ovarian tumours are germ cell and are usually found in young women. Rarely, these tumours occur in other parts of the body, which can make the primary tumour very hard to find. Immunohistochemistry tests (IHC) can identify this type of tumour. The secondary tumour often occurs in lymph nodes in the middle area of the abdomen or chest.

Squamous cell tumours

Squamous cell tumours make up 5 to 10% of CUP. Squamous cells are found in the skin and in the membranes that line the airways close to the outside of the body, such as the nose throat, cervix and anus. The secondary tumours are usually noticed as enlarged lymph nodes in the neck or groin. Local treatments such as surgery and radiotherapy can work well for these tumours.

Neuroendocrine tumours

Neuroendocrine tumours (NETS) make up about 5% of CUP. The most common of these are carcinoid tumours which occur mainly in the small bowel or other parts of the digestive system. NETS may also occur in the lung, pancreas, kidney, ovary and testicle. If this type of CUP can be identified, it can respond very well to treatment.

Adenocarcinoma

Adenocarcinoma makes up at least 3 out of 5 (60%) of all unknown primary cancers. The truer figure may be closer to 90%. Adenocarcinoma is cancer of glandular tissue. The primary tumour occurs in the tubes or ducts of body organs. Studies suggest that in unknown primary adenocarcinoma the secondary cancers are found in the

• Lung – in 27% of cases
• Pancreas – 19%
• Bowel – 11%
• Kidney or adrenal gland – 6% 
• Liver or bile duct – 6%
• Stomach – 5% 
• Ovary or uterus – 3%
• Prostate – 2% 

Of the remaining 20% of unknown primary adenocarcinomas, less than 1% occur in the breast. 

Carcinoma of solid tumours

The primary site of carcinoma of solid tumours is usually the liver, kidney or endocrine glands. They are often grouped with adenocarcinomas.