Therapeutic options for variant renal cancer: a true orphan disease.

Variant or nonclear cell renal cell cancer is a rare disease constituting only approximately 5% to 8% of the metastatic renal cell cancer population. Pathological criteria for the three main variant subtypes, papillary, chromophobe, and collecting duct, have been specified. Nonetheless, there may be subtypes within these variants, many poorly differentiated tumors cannot be reliably classified, and expertise in recognizing specific subtypes is not widespread. Expression analysis and other molecular techniques are beginning to clarify and standardize the pathological classification scheme. Because these classifications are relatively new and the number of patients with any one subtype is limited, little is known about appropriate therapies for patients with metastatic disease. Retrospective series strongly suggest that immunotherapy is not effective in any nonclear cell subtype. Case reports suggest that cytotoxic chemotherapy used for transitional cell cancers may be helpful in patients with collecting duct cancers. A central registry of patients with variant renal cell cancer should be created in which response to various therapies is recorded. Such a registry could provide support for a more formal multi-institutional study investigating a specific drug or regimen.