A patient is considered to have a cancer of unknown primary origin when cancer is detected at one or more sites and routine evaluation fails to identify the primary tumor. Cancer of unknown primary 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.
Because the most common causative primary tumors are those of the testes, lungs, colon and rectum, and pancreas, examination of these areas must be thorough.
Types of testing used to help identify the primary tumor include
Laboratory tests should include a complete blood count (CBC), urinalysis, stool examination for blood, and serum chemistries (including prostate-specific antigen assay in males).
Imaging should be limited to a chest x-ray, abdominal CT, and mammography. Endoscopic examination of the upper and lower gastrointestinal 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 site and can potentially identify tumors arising from the lung, colon, or breast. In addition, immune peroxidase staining for immunoglobulin, chromosome 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) outside lymph nodes. Immunoperoxidase staining of tumor cells for alpha-fetoprotein or beta-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 PSA (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% have 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 year).
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