In recent years, microscopic and other diagnostic techniques have improved dramatically. However, the tissue of<unk>  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<unk>  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<unk><unk>  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<unk><unk> , a PET-CT offers uncertain benefit. The pattern of spread may suggest the location of the<unk>  site. For example, metastatic cancer found in the upper body is more likely to have an<unk>  above the diaphragm, at sites such as the lung and breast. If the metastatic cancer appears first in the lower part of the body, the<unk>  cancer is more likely to be at sites below the diaphragm, such as the pancreas and liver. When the cancer cells are poorly differentiated (that is, they look less evolved than normal cells when viewed under a microscope), the cancer may be either a lymphoma or a germ cell tumor. Lymphomas begin in the lymphatic system. Germ cell tumors usually begin in the ovaries and testes. In patients in whom the<unk>  cancer is eventually found, the lung and pancreas are the most common<unk>  cancer sites. CUP also may be traced to the breast, prostate, colon, or rectum as the<unk>  site. Sometimes, however, even when doctors use very sophisticated methods to try to identify the<unk>  site, the part of the body the cancer cells came from cannot be determined. About 2 to 4 percent of all cancer patients have a cancer whose<unk>  site is never found. Identifying the<unk>  tumor site is important because knowing its location and type often helps doctors plan the best treatment. Treatment that is specific to the suspected type of cancer is likely to be more effective. Still, when diagnostic tests have not identified the<unk>  site, doctors must decide whether the potential benefits of more extensive testing outweigh a patient's discomfort, possible complications, and the financial costs. Immunohistochemical testing Antibodies may be used to determine the expression of protein markers on the surface of cancer cells. Often the expression of these antigens is similar to the tissue that the cancer grew from, so immunohistochemical testing sometimes helps to identify the source of the cancer. Individual tests often do not provide definitive answers, but sometimes patterns may be observed, suggesting a particular site of<unk>  (e.g. lung, colon, etc.). Immunohistochemical testing suggests a single source of cancer<unk>  in about one in four cases of CUP. However, there is a lack of definitive research data showing that treatment guided by information from immunohistochemical testing improves outcomes or long-term prognosis. Classification CUP may be classified by its appearance under a light microscope. The majority of cancers of<unk><unk> , about 90%, are adenocarcinomas, with 60% appearing as moderately to well-differentiated adenocarcinoma, while about 30% are poorly differentiated adenocarcinoma. The term adenocarcinoma refers to cancer that begins in the cells in glandular structures in the lining or covering of certain organs in the body. Common<unk>  sites for adenocarcinomas include the lung, pancreas, breast, prostate, stomach, liver, and colon. The remaining 10 percent are either poorly or undifferentiated malignant neoplasms (5%), or squamous cell carcinomas (5%). Rarely, CUP may appear as neuroendocrine tumors, or mixed tumors, such as sarcomatoid, basaloid, or adenosquamous carcinomas.
Cancer of unknown primary origin
Metastatic breast cancer
Metastatic carcinoma
Non-Hodgkin lymphoma
Hodgkin lymphoma
Large cell neuroendocrine carcinoma of the lung
Radiation-induced cancer
Atypical pulmonary carcinoid tumour