Unknown Source Cancer Symptoms

This article describes symptoms of cancers that arise from an unknown source.  This may seem like a strange class of disease but it makes up about 5% of all cancers diagnosed.  There is a symptom that prompts investigated and some evidence of cancer spread is found without knowledge of where the cancer spread from.  With further investigation the source may be found but sometimes it cannot be found.

Cancers of unknown sources (more commonly referred to as cancer of unknown primary site) might arise from a myriad of sources.  Possible sources for this type of cancer are as follows:

Enlarged lymph nodes: The main symptom (sign really but for the purposes of these informational articles these two terms are often used interchangeably) that causes recognition of an unknown cancer is lymph node swelling.  The general term for enlarged lymph nodes is lymphadenopathy.  Lymph nodes occur in clusters in different areas of the body where they serve to drain lymphatic fluid from that region of the body.  There are large lymph node basins in the groin, armpits and neck.  There are also significant lymph node collections near the veins that drain the intestine and also many that line the pelvis.

The ones that come to the attention of the person with cancer are the ones that are readily seen or felt such as those in the neck or armpit.  Swollen lymph nodes are common and all of us get them from time to time.  The purpose of the lymph nodes is to act as checkpoints for lymph fluid flow to help screen for foreign invaders such as bacteria and to process these as well.  With infection or injury the lymph nodes will swell, will be tender to touch and will go down after the problem is resolved.  The swelling of lymph nodes that occurs when they are congested with cancer from a nearby source is usually not tender and tend to be firm, rubbery or even very hard.

Sometimes the location of the swelling can suggest where the primary cancer is.  For example, a woman who finds a large firm lymph nodes (or nodes) in the left armpit may have a cancer in the left breast she does not know of.  If a breast exam or mammogram does not reveal a tumor in the adjacent breast than a more extensive search will be needed and this would be classified a tumor of unknown origin. This term will be used after cancer has been proven in some way generally involving getting a biopsy or sample of cells from the enlarged lymph node.

As previously stated, an enlarged lymph node can be due to infection and a cancer evaluation or diagnosis will not be entertained until a cancer has been proven to be present in some fashion.  The label of unknown primary does not mean that the main tumor cannot be found, it implies that it is very difficult to find or has not been found yet.  In some circumstances the primary tumor cannot be found. This creates a dilemma.  For example, consider the above scenario with a large lymph node in the left armpit of a woman with proven cancer in it.  Now her evaluation such as examination and mammogram shows no evidence of breast cancer.  The next step would be to further evaluate the lymph node to see if the type of cancer or tissue of origin can be identified in some way.

The most common cancer cell types with cancer of unknown source include:

1) Adenocarcinoma,

2) Squamous cell carcinoma,

3) Poorly differentiated carcinoma,

4) Neuroendocrine carcinoma and

5) Poorly differentiated cancer which cannot be further classified.

In the above example of the woman with a cancer containing axillary lymph node and no detectable breast tumor on x-ray, this woman would likely be recommended to undergo removal of all the lymph nodes in the armpit, further types of imaging and possibly removal of the left breast as well even if further imaging shows no breast tumor.  In this specific situation, up to 50% of women will be found to have a small breast cancer that was missed by the imaging. Thus the term “unknown source” or “unknown primary” is a bit of a misnomer and should practically be interpreted as “we can’t locate the cancer yet.”   The key point is that firm, enlarged, non-tender lymph nodes should not be ignored and should be brought to the attention of your doctor for further investigations such as the ones outlined above. 

Other common symptoms or presentation scenarios that lead to a diagnosis of cancer with an unknown primary would be a pathologic fracture, abdominal pain with tumor in the liver or lungs that on biopsy seems to have spread from somewhere else, fevers, night sweats, or unexplained weight loss.  Other symptoms that might prompt investigation are a change in bowel habits such as severe constipation, blood in the stool or blood in the urine.  These symptoms are fairly non-specific but should not be ignored if persistent.


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  2. Greco FA, Pavlidis N. Treatment for patients with unknown primary carcinoma and unfavorable prognostic factors. SeminOncol 2009; 36:65.
  3. www.cancer.gov/cancertopics/pdq/treatment/unknownprimary/Patient/page1
  4. www.cancer.gov/cancertopics/types/unknownprimary
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  6. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.