These evaluations provide guidance for the appropriate clinical evaluation that ensues. An obvious corollary to the pathologist's role is the critical interaction between the pathologist, oncologist, and primary physician. The complexity of the pathologic evaluation tends to be inversely related to the degree of differentiation of the tumor. For well or moderately differentiated tumors, the pathologic diagnosis of an epithelial cancer versus lymphoma, sarcoma, melanoma, or a germ cell tumor, for instance, is often readily apparent. Commonly used stains such as mucicarmine or diastase sensitive Periodic Acid Schiff can be important in confirming the diagnosis of certain tumors of gastrointestinal or renal origin.
Special studies can help in distinguishing more poorly differentiated tumors.
Microsatellite analysis has been used to assess genetic alterations in cervical lymph nodes. These alterations were identical to those observed in 18 patients with normal mucosal histology and malignant nodes, suggesting a site of primary tumor origin. Most often prostate cancer is found as an obvious prostatic cancer by digital rectal examination. These cancers, as mentioned above, appear to have a different metastatic distribution than the predominant bony distribution that is generally encountered in prostate cancer. Thus, when there is any suspicion that the primary disease may have arisen from the prostate, the specificity of the test and the availability of relatively nontoxic hormonal approaches emphasize the need to evaluate this diagnostic possibility in the CUP setting.