Persistent Challenges in Nuclear Grading of Clear Cell Renal Cell Carcinoma: A Survey of Pathologists

BackgroundGrading of clear cell renal cell carcinoma now focuses on the prominence of the nucleolus; however, there may be variability in how pathologists interpret this criterion.MethodsAn online survey was distributed via email and social media to pathologists.ResultsExcluding trainees, 91 responses were received, including 77 self-identified as genitourinary (GU) and 14 non-GU. Most did not require nucleoli to be eosinophilic when determining visibility (78% GU and 71% non-GU). Most indicated that nucleoli visualized at 40× magnification at all would be considered grade 2, even if nucleoli are not eosinophilic/large (69% GU and 57% non-GU), with similar results for grade 2 versus 3 (10×) at 61% GU and 71% non-GU. For a photomicrograph at 40× magnification with visible but basophilic nucleoli, most reported grade 2 (96% GU and 79% non-GU). For an image with more prominent nucleoli described as visible at 10×, 84% of GU and 71% non-GU reported grade 3. Respondents estimated using grade 1 in 5% or less of resection specimens (76% GU, 58% non-GU). For multinucleated cells with bland individual nuclei, most (83% GU, 86% non-GU) would not consider this grade 4.ConclusionAlthough grading guidelines indicate that renal cell carcinoma nucleoli should be prominent/eosinophilic to assign grade 2 or 3, most pathologists assign the higher grade if nucleoli are visible at all. Further refinement is needed for grading cells with multiple but non-bizarre nuclei.