Unknown Source – Tissue and Systems

This article describes bodily systems that may be involved with cancers with an unknown source.  It may seem like an oxymoron to be diagnosed with a cancer without knowing where the cancer is but it actually is not infrequent.  About 5% of all cancers diagnosed have an unknown source.  For example, an older man develops a “knot” in the left side of the neck that is firm and does not go away.  A biopsy or sample of cells is obtained and this sample says that this lymph node has adenocarcinoma type cancer in it.  The question then becomes where did this cancer spread from.

There are rare tumors that grow directly from or within a lymph node, however most cancer in lymph nodes is cancer that has spread from its places of origin or home tissue / organ.  Sometimes the answer is obvious such as a woman who is found to have a right breast tumor after she notices a lump in her right armpit that represents lymph nodes swollen with cancer cells from the breast tumor.  If the source is not found, or not obvious, then the person’s cancer falls into this category of unknown primary source.  It is not that the source cannot be known, but that it is not obvious or “occult” in medical parlance.

The anatomy and systems involved with unknown primary cancer is thus virtually any system in the body but the most common target of these cancers is the lymph nodes.  The lymph node system area series of drainage tubes that collect water and other small particles that is outside cells and vessels.  The lymphatic drainage than is sent through a series of checkpoints that screen for foreign invaders such as bacteria at period lymph node stations.  Lymph nodes tend to cluster in areas such as the armpits, groin, sides of the neck and deep abdomen.

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

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:

These sources are sometimes determined by markers or specific tests run on the cancer biopsy that helps to pinpoint the possible organ of origin although these are not always very accurate.  The other way to help determine the tissue of origin is to obtain blood tests known as tumor markers.  With some cancers, certain proteins are shed into the blood and can be measured subsequently.  These markers are not very specific and are not a good way to screen for cancer.  However, if one is very elevated it might point to the possible source of the cancer.  A cancer is this category will be searched for after it has been documented that it spread somewhere.  For example, a tumor of the lung is removed and is found to have features under the microscope that look similar to the skin cancer melanoma.  In this situation a search would be carried out to try and find the source skin cancer.

Most tumor markers are used for surveillance after a cancer has been treated or removed.  The idea is that if the cancer comes back then perhaps the marker level will start to rise.  For example, a man has a colon cancer diagnosed and has a CEA level of 100.  His cancer is removed with an operation and the CEA level falls to 2 (a normal range).  Now one year later he has a new spot appear in the liver on a CAT scan and his CEA level rises to 53 – this strongly indicates the cancer has come back.  Some of the commonly used tumor markers to help assess the health of organ systems and to rarely screen for a particular cancer are as follows:

  • AFP – useful for liver cancer or germ cell tumors of the gonads
  • Beta-HCG – Also useful for germ cell tumors of the gonads
  • CA 15-3 – Used for breast cancer mostly, be less commonly currently
  • CA 19-9 – Commonly used to follow pancreatic cancers
  • CA 125 – Used for cancer of the ovary mostly
  • Calcitonin – A marker used for a type of thyroid cancer known as medullary
  • CEA – Used to follow bowel tumors, mostly colon cancers
  • PSA – Used for prostate cancer
  • Several other that are used rarely

It is important to emphasize that these tests do diagnose or prove that a cancer is present or the origin of the cancer when present.  It is just another clue or piece of evidence that can be used in conjunction with other data.

This is a frustrating situation to be in because sometimes treatment must begin without the primary cancer being found or even sub-type determined.  For example, a person who has a lymph node of the neck that shows squamous cell carcinoma that has no primary tumor identified may still get surgery for that area of the neck as well as chemotherapy and radiation to the head and neck area.


  1. Greco FA, Hainsworth JD. Introduction: unknown primary cancer. SeminOncol 2009; 36:6.
  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
  5. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.