Grading of renal cell carcinoma

The grading of renal cell carcinoma, when done consistently by surgical pathologists who are familiar with a particular grading system, has prognostic value for postnephrectomy patients who are initially found to have low stage (e.g., Stage I) tumors. We believe that most existing grading systems, when applied by experienced pathologists who are knowledgeable in the relevant criteria and working in an established urologic practice, have merit and likely all provide significant prognostic information. An ideal grading system needs to be established. A three-grade system is recommended. Nuclear grading systems are the most widely used systems and the available evidence in the literature suggests that nuclear grade is a better prognostic indicator than other types of grading that do not use nuclear criteria. Nuclear grade should be based on the worst area identified as having disease. The size of the worst area needs to be defined. Nuclear grading has prognostic value for conventional (clear cell) and papillary renal cell carcinoma. The data supporting the validity of nuclear grading for chromophobe carcinoma is not well established, but it seems reasonable to grade these tumors for ongoing clinicopathologic studies. Oncocytoma is a benign tumor that should not be graded. We recognize that the Fuhrman nuclear grading system is probably the most widely used system in North America and that there are studies that support its clinical relevance as a prognostic factor. We also recognize there are problems with this and all grading systems. Experience indicates some problems with reproducibility. Most importantly, consistent recognition of nucleoli and assessment of their size may be problematic, particularly in non-formalin-fixed or poorly fixed tissue. For those who use the Fuhrman system, collapsing the four grades into three grades may be useful. The experience of the group members and the prognostic data indicate that grouping Grades 1 and 2 together is a potential improvement. Grading is always a subjective exercise. Incorporation of additional morphologic parameters, such as the number or presence of mitoses, may lead to an improved grading system. The development of a prognostic index that combines nuclear grade with more objective parameters, such as proliferation markers and nuclear morphometric analysis, should be further investigated. The detection of preneoplastic lesions in the kidney is of scientific interest and may be relevant to patient management in the following situations: identification of a small, solid renal nodule by imaging techniques consideration of a partial nephrectomy assessment of a donor kidney for transplantation The issue of preneoplastic lesions in the kidney is relevant in several pathologic situations: hereditary renal cell carcinoma, clear cell type and papillary type putative intratubular epithelial dysplasia putative intracystic epithelial dysplasia definition of the adenoma-carcinoma continuum Molecular analysis of precursor lesions and potential precursor lesions is necessary for acceptance of these lesions as true precursors of cancer. We believe that: Available clinical, histologic, and molecular evidence indicates that renal cysts with clear cells in patients with von Hippel-Lindau (VHL) syndrome are precursor lesions. Identification of the precursor lesions in hereditary forms of renal cell carcinoma may lead to the identification of precursor lesions for sporadic renal cell carcinoma. For example, correlating the histologic changes associated with developing cystic renal cell carcinoma in the multicystic kidneys of VHL syndrome may provide criteria for the classification of acquired renal cysts with different degrees of clear cell epithelial proliferation. Analysis of the VHL gene in cysts with clear cells in sporadic cases may be helpful. Acquired renal cysts with a nodular epithelial proliferation of clear cells, or with evidence of mural invasion by clear cells, should be classified as cystic renal cell carcinoma. A cyst lined by a single or double cell lining of clear cells should be assessed conservatively and is probably not a malignant tumor. Intratubular epithelial dysplasia needs further study to determine the spectrum of its histologic features, distribution, and frequency in kidneys with and without established renal cell carcinoma. A practical working definition of papillary renal adenoma is the following: a low grade tubulopapillary tumor that is <0.5 cm with no clear cells. Moreover, this definition should not preclude the possibility of identifying an adenoma of larger size, as our evolving understanding of the genetic factors in renal neoplasia may allow us to recognize such a tumor. Solid clear cell tumors of any size should be classified as carcinoma. * Workgroup participant.