Cancer of unknown primary origin

Cancer of unknown primary origin (CUP) is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a primary tumor. Cancer of unknown primary origin (CUP) is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a primary tumor. CUP is found in about 3 to 5% of all people diagnosed with invasive cancer, and carries a poor prognosis in most (80 to 85%) of those circumstances. The other 15 to 20% of patients, however, have a relatively long survival with appropriate treatment. Most cancers typically present as a single primary tumor. Over the course of time—particularly if the primary tumor is left untreated—smaller 'satellite' tumors will appear at other places in the body, a phenomenon known as metastasis. Less commonly, a metastatic tumor is found first; but in most such cases, the primary tumor can then be located via examination and testing. Rarely (3-5% of the time), the primary tumor cannot be found because it is too small, or because it has regressed due to immune system activity or other factors. In such situations a diagnosis of cancer of unknown primary origin (CUP) is made. CUP usually comes to attention because of masses or swellings found somewhere in the body, either by physical examination or on medical imaging performed for another indication. The disease typically develops rapidly, and metastases may occur in places in the body that are otherwise unusual. Comprehensive physical examination is part of the process to identify a possible primary source of cancer; this should include the breasts, lymph nodes, the skin, external genitals, as well as an internal examination of the rectum and of the pelvic organs. The location of metastases may be a clue as to the underlying source, even if this cannot be found on investigations. For instance, a woman in whom there is axillary lymphadenopathy (swelling in the lymph nodes of the armpit) it is likely that the cancer originated in the breast, and men with lymph node deposits in the mediastinum of the chest and/or retroperitoneal space of the abdomen may have a germ cell tumor. Cancer of unknown primary source is not a single type of cancer, although researchers have attempted to find a common characteristic that explains why a cancer might spread very early without causing symptoms at the site of origin. It is generally accepted that cancer of unknown primary site exists because the primary tumor is not identified due to clinical or technological inefficiencies, or because the primary tumor regresses or stays dormant after spreading the cancer cells that generate the metastases. This view is widely accepted in oncology; in fact, these cancers are also referred to as occult primary tumors. Because the site of the primary tumor usually dictates the treatment and expected outcome, this view may help create uncertainty and anxiety among health professionals and patients, who may feel that their evaluation has been incomplete. Because stem cells have a natural ability to migrate and also play a key role in cancer development, it has been proposed that a cancer of unknown primary site may form when deregulated, premalignant or cancerous stem cells migrate away from their natural tissue and give rise to a cancer in the new site before or without generating a tumor in their original tissue. Forming a tumor in a tissue is not a prerequisite for stem cells to move away from that tissue. Stem cells can migrate from their natural tissue and initiate a cancer in the new site before generating a detectable tumor in their natural tissue. In this case, the primary tumor could be identified after some time. However, stem cells can also migrate away from their natural tissue without generating a cancer there. In this case, the “primary tumor” would never exist (see Figure). This can explain why the primary site is not identified even on postmortem examination in many patients with these cancers. This view of CUP may provide relief to health professionals and patients. After a detailed imaging and pathologic analysis, oncologists can tell their patients with CUP that metastasis does not always involve the formation of a primary tumor, and that their diagnostic evaluation is complete. In recent years, microscopic and other diagnostic techniques have improved dramatically. However, the tissue of origin can be still determined only about in one in four cases of CUPs with these methods. In some cases, the part of the body where cancer cells are first discovered helps the doctor decide which diagnostic tests will be most helpful. Additional clues which may be helpful in determining the primary site include the pattern of spread, and the cell type, which is based on its appearance under a microscope (histology). The initial work-up of a cancer of unknown primary includes a CT scan of the chest, abdomen, and pelvis, with IV contrast. Women with enlarged lymph nodes (lymphadenopathy) confined to the axillary region with CUP should have a mammogram or ultrasound to evaluate for possible breast cancer. If those imaging studies are normal, then an MRI of the breast may be appropriate. A PET CT scan should be done for squamous cell carcinoma involving lymph nodes of the neck region. For other types of cancer of unknown primary, a PET-CT offers uncertain benefit.