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    Origin Unknown

    By Richard C. Frank, MD


    I recently saw a 79 year old woman in good health who detected a large mass in her abdomen. A CAT scan showed multiple tumors involving her liver and swollen lymph nodes in other parts of her abdomen. A liver biopsy showed cancer-”carcinoma cells”-but not those derived from the liver, so she did not have liver cancer. Further testing by the pathology lab did not specify the type of cancer and suggested the cancer to the liver from another “primary” site in the body. “So where did the cancer start? What type of cancer do I have?” the patient asked me. I told her we would perform various tests to search for a possible site of origin but that we might not find a clear primary site. If this was the case, she would have what is call “carcinoma of unknown primary site” or CUP. “Won’t you know for sure where the cancer started? How can you treat me without knowing what type of cancer I have?” she asked in disbelief. Very appropriate questions indeed. Doctors hate not having answers; we appear incompetent at these times. I told her we would try to arrive at a definite answer.

    CUP is a type of cancer very familiar to oncologists although is not talked about at all in the media.  Only rarely has CUP been linked to a famous person (the legendary college basketball coach James Valvano “JimmyV” was diagnosed with it). Most people have never heard of CUP until they or a loved one has to confront it. It is a cancer that is difficult to understand and also difficult to treat.

    The category of cancers called “carcinomas,” represent the most common types of cancer:  Breast, lung, prostate, colon, ovarian, pancreatic, kidney cancers and most other cancers are carcinomas. Carcinomas arise from the glands and organs of our body, in contrast to sarcomas, which arise from bone, muscle and nerves, or the cancers derived from the bone marrow- lymphoma, leukemia, multiple myeloma. The problem with carcinoma of unknown primary site is that it typically becomes detectable when tumors are found in different regions of the body but the organ from which those tumors derived cannot be determined. In medical terms, the metastases of cancer are found but the primary site cannot be located (see my last post for a discussion of breast cancer metastases).

    In the case of my patient, we searched for a primary site:  The CAT scan showed no tumor in her pancreas and a colonoscopy and upper endoscopy found no tumors in the colon, stomach or esophagus. A mammogram was clear, ruling out a breast cancer and a CAT scan of the chest showed nothing to suggest that the primary was lung cancer. We even performed a PET scan that showed cancer only in the liver and lymph nodes, nothing we didn’t know. So, we were stuck. But not completely.

    I had the patient’s tumor specimen sent to a lab called Pathwork Diagnostic. This company performs a genetic analysis of a metastatic tumor  and matches its genetic profile to those known for the various types of cancers, such as breast, colon, bladder, ovary, etc. The test result matched her cancer closest to that derived from the bile ducts, enabling us to make a diagnosis of biliary tract cancer. The liver contains bile ducts that carry bile from the liver to the main, common bile duct, which empties bile into the intestines where it works to digest food.  I treated her with a chemotherapy regimen directed towards this type of cancer (called FOLFOX) and she is enjoying excellent cancer control and a good quality of life.

    This approach was recently validated in an article in the Journal of Clinical Oncology. Researchers found that patients with CUP who had an identifiable primary site based on a genetic analysis lived longer than patients treated with traditional CUP chemotherapy regimens that are not tumor directed. This paper should usher in the more widespread use of gene testing of CUP tumors, hopefully leading to better outcomes for patients.


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