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Metastatic Carcinoma of Unknown Primary Origin
A patient is considered to have carcinoma of unknown primary origin when a tumor is detected at one or more metastatic sites and routine evaluation fails to identify a primary tumor. Metastatic carcinoma of unknown primary origin constitutes up to 7% of all cancers and poses a therapeutic dilemma, because cancer treatment is typically determined by the specific primary tissue of origin.
The most common causative primary tumors are those of the testes, lungs, colon and rectum, and pancreas. Examination of these areas should be thorough.
Types of testing used to help specify the primary site include
Laboratory tests should include a CBC, urinalysis, stool examination for occult blood, and serum chemistries (including prostate-specific antigen assays in males).
Imaging should be limited to a chest x-ray, abdominal CT, and mammography. Endoscopic examination of the upper and lower GI tract should be done if blood is present in the stool.
Increasing numbers of immunocytochemical stains can be used to test available cancerous tissue to help determine the primary tissue site and can potentially identify tumors arising from the lung, colon, or breast. In addition, immunoperoxidase staining for immunoglobulin, chromosomal studies, and immunophenotyping may help diagnose the various subtypes of malignant lymphomas, which may be difficult to recognize and differentiate from other tumors (even carcinomas) when they manifest outside lymph nodes. Immunoperoxidase staining of tumor cells for α-fetoprotein or β-human chorionic gonadotropin may suggest readily treatable germ cell tumors. Tissue analysis for estrogen and progesterone receptors helps identify breast cancer, and immunoperoxidase staining for prostate-specific antigen helps identify prostate cancer.
Even if a precise histologic diagnosis cannot be made, a constellation of findings may suggest an origin. Poorly differentiated carcinomas near or at midline regions of the mediastinum or retroperitoneum in young or middle-aged males should be considered germ cell neoplasms—even in the absence of a testicular mass. Patients with this type of carcinoma should be treated with a cisplatin-based regimen, because nearly 50% of such patients experience long disease-free intervals. For most other unknown primary cancers, the responses to this regimen and to other multidrug chemotherapy regimens are modest and of brief duration (eg, median survival < 1 yr).
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