Abstract

The classification must be based on morphology yet be in line with the genetic facts as they are presently understood, and in line with the evolution of the neoplasms. The terms should be simple, unambiguous, and reflect a salient morphologic feature of the neoplasm. The terms should be consistent with historic usage when possible, but when the meaning has changed significantly, they should be replaced with a new term. A term is not a description and cannot encompass all of the morphologic variations of a neoplasm. The proposed classifications follows. Papillary adenoma is the most common neoplasm of the renal tubular epithelium and is a frequent incidental finding in adult kidneys. Most are <3 mm. Lesions <5 mm should be considered papillary adenoma. Their microscopic morphology resembles low grade papillary renal cell carcinoma to the extent that there are no reliable cytologic criteria to distinguish individual examples from small carcinoma. That they are benign is inferred from their high frequency compared with the frequency of progressive papillary carcinoma. Their known genetic abnormalities (typically -Y, +7, and +17) are similar to, but less extensive than, those of progressive papillary renal cell carcinoma. Renal oncocytoma comprises approximately 5% of renal tubular neoplasms in surgical series. It is typically comprised of cells with abundant eosinophilic cytoplasm that is filled with mitochondria. The growth pattern is solid or islands in an edematous stroma. Approximately 5% contain tubules and cysts. Genetically, two groups can be distinguished: one with losses of chromosomes Y and 1 and one with translocation involving breakpoint 11q13. Grading is not appropriate for these benign tumors. Metanephric adenoma and metanephric adenofibroma are closely related neoplasms comprised predominantly of small tubules lined by cuboidal epithelial cells, which is reminiscent of of Wilms' tumor. Sometimes the tubules are compressed, giving a solid appearance. Short papillae, reminiscent of the "glomeruloid" bodies of Wilms' tumor, often are present. Because the number of cases reported is small, their inclusion as benign is provisional. The term "metanephric" lacks precision because all neoplasms of the human kidney are metanephric tumors. However, its usage is now sufficiently common to justify its retention. Originally called "nephrogenic adenofibroma," this composite epithelial and stromal tumor apparently is closely related to metanephric adenoma, and the designation "metanephric adenofibroma" better reflects this relationship. Conventional (clear cell) renal carcinoma is the most common carcinoma of the renal tubular epithelium accounting for approximately 70% of cases in surgical series. These have been called "nonpapillary" in a genetic classification. The great majority of these carcinomas are comprised predominantly of cells with clear cytoplasm in routine sections, although foci in which the cells have eosinophilic cytoplasm are common. These carcinomas have a characteristic delicate, branching vasculature and commonly have solid and cystic architectural patterns. Rarely, the cysts dominate and only a small population of clear cells is present. Genetically, these tumors are characterized by loss of genetic material in 3p; 50% show somatic mutations in the von Hippel-Lindau (VHL) gene, and an additional 10-20% of clear cell renal carcinomas show inactivation of the VHL gene by epigenetic changes comprising (hypermethylation). Sarcomatoid change occurs in approximately 5% of these carcinomas. Papillary renal carcinoma is the second most common carcinoma of the renal tubular epithelium, comprising 10-15% of cases in most surgical series. These were called "chromophil renal cell carcinoma" in the Mainz classification and have been called "tubulopapillary carcinoma" as well. Papillary architecture predominates in the great majority of these tumors and is present, at least focally, in almost all. The cells covering the papillae range from small to large and have variable cytoplasmic staining. Psammoma bodies, foamy macrophages, and edema fluid are common in the papillary cores. Genetically, these tumors are characterized by trisomies (chromosomes 3q, 7, 12, 16, 17, and 20) and loss of the Y chromosome. These genetic features, when present, support the diagnosis of papillary renal carcinoma even when papillae are not prominent. Conversely, neoplasms lacking these genetic features (e.g., some Wilms' tumors) should not be designated as papillary renal carcinoma even when papillary architecture is prominent. Chromophobe renal carcinoma is the third most common carcinoma of the renal tubular epithelium and accounts for approximately 5% of cases in most surgical series. Morphologically, its cells have variable amounts of pale or eosinophilic cytoplasm that stains blue with Hale's colloidal iron stain and contains many microvesicles. In routine sections, the cytoplasm tends to condense near the cell membrane, producing a halo around the nucleus. The cells vary widely in size, and often there is a concentration of the largest cells along small blood vessels. Solid architecture is most common. Genetically, chromophobe renal cell carcinoma is characterized by monosomy of multiple chromosomes (1, 2, 6, 10, 13, 17, and 21) and hypodiploidy. Collecting duct carcinoma accounts for <1% of surgical series and is a term that has been applied to carcinoma with a wide variety of appearances. The best accepted morphology is one of irregular channels lined by highly atypical epithelium that sometimes has a hobnail appearance. The channels are set in an inflamed desmoplastic stroma. This appearance merges with that of a recently recognized variant, medullary carcinoma of the kidney, which is believed to arise from the collecting ducts of the renal medulla and is associated with sickle cell trait. The main difficulty with assigning tumors to this category is demonstrating origin in the collecting ducts. Small tumors that can be observed to arise from a medullary pyramid (as opposed to merely centrally in the kidney, because the columns of Bertin bring cortical tissue down to the renal sinus) are good candidates. Association with dysplastic changes in neighboring collecting ducts and affinity for Ulex europaeus lectin also support the concept of collecting duct origin in a renal carcinoma. Because collecting duct carcinoma is rare, and the published cases are morphologically heterogeneous, it is not surprising that no consistent pattern of genetic abnormalities has been established for it. Renal cell carcinoma, unclassified is a diagnostic category to which renal carcinomas should be assigned when they do not fit readily into one of the other categories. In some surgical series, this group has amounted to approximately 4-5% of cases. Because this category must contain tumors with a variety of appearances and genetic lesions, it is not susceptible to a limiting definition. However, examples of features that might prompt assignment of a carcinoma to this category include: apparent composites of recognized types, sarcomatoid cells without recognizable epithelial elements, mucin production, mixtures of epithelial and stromal elements, and unrecognizable cell types. Sarcomatoid change has been found to arise in all of the types of carcinoma in the classification, as well as in urothelial carcinoma of the renal pelvic mucosa. Because there is no evidence that it arises de novo as sarcomatoid carcinoma, it is not viewed as a type of its own, but rather as a manifestation of high grade carcinoma of the type from which it arose. Occasionally, the sarcomatoid elements overgrow the antecedent carcinoma to the extent that it cannot be recognized; such tumors are appropriately assigned to the unclassified category. With these principles of classification in mind, some terms that have been used in the past are no longer useful. Over the past 20 years, oncocytoma and parts of chromophobe renal cell carcinoma, papillary renal cell carcinoma, collecting duct carcinoma, and epithelioid angiomyolipoma have been extracted from what was called "granular cell renal cell carcinoma." This has left that term with no precise or generally understood meaning; therefore, the authors recommend that it not be used. * Workgroup participant.