Case 4 -

Chromophobe Renal Cell Carcinoma with Sarcomatoid Change John N Eble, M.D. Holger Moch, M.D.

Case history: A 57 year-old man was evaluated for weight loss and malaise. Radiographic evaluation showed his right kidney to be replaced by a large mass. Radical nephrectomy was done. Four weeks later, a chest X-ray showed multiple nodules in his lungs. Macroscopic findings: The cut surface of the tumor was heterogeneous, with areas of soft tan tissue and extensive areas of firm whitish tissue. Perirenal fat was invaded by the tumor. Diagnosis: Chromophobe renal cell carcinoma with sarcomatoid change Sarcomatoid change occurs in all of the major types of renal cell carcinoma: clear cell, papillary, chromophobe, and collecting duct. It also occurs in urothelial carcinoma arising in the renal pelvis. When the antecedent carcinoma is overgrown by the sarcomatoid elements, the proper diagnosis is renal cell carcinoma, unclassified. While sarcomatoid change is not included in the nuclear grading system widely used for renal cell carcinomas, it is prognostically important because patients with sarcomatoid renal cell carcinoma fare very poorly and similarly to patients with grade 4 renal cell carcinoma. Among the 108 patients with sarcomatoid renal cell carcinoma seen at the M.D. Anderson Cancer Center, the median survival was 9 months; with follow up ranging from 22 to 97 months, 90% died of their cancers. At the Mayo Clinic, 94 of 120 patients with sarcomatoid renal cell carcinoma died of the disease. The median survival was 8 months, and the 5-year cancer-specific survival was 15%. When enough of the antecedent carcinoma is present to be diagnosed, there usually is little problem in recognizing what is going on and in rendering a diagnosis phrased along these lines: "Chromophobe renal cell carcinoma with sarcomatoid change." When the antecedent carcinoma cannot be diagnosed, the current classification system calls for a diagnosis of "renal cell carcinoma, unclassified." Cases like that account for much of the mortality of patients with renal cell, unclassified in published series. A sarcomatoid carcinoma should be relegated to "renal cell carcinoma, unclassified" only after extensive sampling has failed to reveal the antecedent carcinoma. By convention, if there is urothelial carcinoma in situ in the mucosa of the renal pelvis, the sarcomatoid carcinoma is diagnosed as urothelial carcinoma with sarcomatoid change. In approaching a tumor when the antecedent carcinoma has not been found, the first step should be to return to the specimen and take more samples from all of the different-appearing areas, from different geographic areas, and from the renal pelvic mucosa. Quite often, this approach will lead to the precise diagnosis. If this fails, then the question of a primary renal sarcoma arises. Since sarcomatoid carcinomas are more common than primary renal sarcomas, the usual immunohistochemical approach is to seek evidence of the epithelial roots of the tumor. While epithelial membrane antigen and CAM5.2 often are positive in renal cell carcinoma, cytokeratin AE1/3 is more frequently positive in sarcomatoid areas. However, there is considerable variability from tumor to tumor so applying all 3 procedures is recommended. References Mian BM, Bhadamkar N, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol 167: 65-70, 2002 Cheville JC, Lohse CM, et al. Sarcomatoid renal cell carcinoma, an examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol 28: 435-441, 2004 DeLong W, Grignon DJ et al. Sarcomatoid renal cell carcinoma, an immunohistochemical study of 18 cases. Arch Pathol Lab Med 117: 636-640, 1993