Persistent challenges in nuclear grading of clear cell renal cell carcinoma

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Conference Proceeding

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Modern Pathology


Background: The World Health Organization (WHO) and International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma now focuses on nucleolar prominence as the main criterion. We aimed to investigate how this system is implemented in certain scenarios. Design: An online survey was circulated via e-mail to a group of genitourinary pathology specialists (GU) and shared publicly via social media (including via Twitter and 3 Facebook pathology groups, 2 focusing on urologic pathology and 1 large general surgical pathology group). The survey included a mixture of descriptive questions and images. Results: In total, 91 responses were received from non-trainee pathologists, 77 self-identified as GU and 14 as non-GU. The vast majority reported using the ISUP/WHO system rather than Fuhrman (92% GU, 79% non-GU). Most reported not requiring nucleoli to be eosinophilic when determining visibility (77% GU and 72% non-GU). Most indicated that nucleoli visualized at high magnification at all (40×, composing an entire high-power field), would be considered grade 2, even if nucleoli are not eosinophilic / large (67% GU and 57% non- GU). Distinguishing grade 2 from 3 (10× magnification) yielded a similar response with 63% GU and 61% non-GU. When shown a photomicrograph taken at 40× magnification with visible but relatively small basophilic nucleoli (Figure A), most reported grade 2 (93% GU and 79% non-GU). For an image with more prominent nucleoli described as visible at 10×, 82% of GU and 71% non-GU reported grade 3. Respondents estimated using grade 1 in 5% or less of resection cases (73% GU, 57% non-GU, with one-third estimating 2% of cases or less). For multinucleated cells with bland individual nuclei (Figure B), most (84% GU, 86% non-GU) would not consider this grade 4. (Figure presented) Conclusions: The ISUP/WHO grading system for renal cell carcinoma has gained relatively widespread acceptance; however, some uncertainty remains regarding the degree of nucleolar prominence that warrants a higher grade. Despite the official descriptions requiring nucleoli to be eosinophilic, most pathologists do not require this in practice. Most respondents estimate that they use grade 1 very rarely. It is not entirely clear how tumor cells with multiple, non-bizarre nuclei should be handled, although most do not consider this inherently grade 4.





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