{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:10:50Z","timestamp":1788858650692,"version":"build-2803163510"},"reference-count":115,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>A decade into the formal adoption of the World Health Organization (WHO)\/International Society of Urological Pathology (ISUP) grading system for clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC), newer grading concepts, innovative approaches and some issues have emerged. A comprehensive review of the literature on the WHO\/ISUP grading system and other grading approaches for CCRCC and PRCC was conducted. Updates and issues are presented on the following: (1) validation studies on WHO\/ISUP grading; (2) grade elements including heterogeneity, grades 1 versus 2, types of multinucleated tumour cells, \u2018grade spectrum\u2019 of spindle cells, impact of sarcomatoid change in grade 4 RCC, percent (%) high grade, % sarcomatoid change and rhabdoid change versus sarcomatoid change; (3) grade applications including observer agreement, needle biopsy grade accuracy (correlation with nephrectomy grade) and grading of multifocal RCCs; (4) grade in papillary tumours including heterogeneity and on small (\u22641.5\u2009cm) neoplasms; and (5) novel grading or risk categories including incorporation of necrosis into grading and pattern or architectural\u2010based grading. Practice guidance for some of the issues is provided when feasible or where data are sufficient. This review highlights the recent updates and controversies in the use of WHO\/ISUP grading and on novel approaches to grading for CCRCC and PRCC. This review may serve as a best practice guide in addressing some of the grading issues and will help identify gaps in our understanding and use of grading for CCRCC and PRCC that can inform future research.<\/jats:p>","DOI":"10.1111\/his.70177","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:14:56Z","timestamp":1780046096000},"page":"574-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Updates and controversies in contemporary grading of clear cell renal cell carcinoma and papillary renal cell carcinoma"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5839-6640","authenticated-orcid":false,"given":"Gladell P.","family":"Paner","sequence":"first","affiliation":[{"name":"Department of Pathology and Surgery (Urology) University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-3634","authenticated-orcid":false,"given":"Mahul. B.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Tennessee Health Science System  Memphis Tennessee USA"},{"name":"Department of Urology USC Keck School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1793-2732","authenticated-orcid":false,"given":"Jung Woo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Surgery (Urology) University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Surgery (Urology), Brown University Warren Alpert Medical School, Legorreta Cancer Center Brown University Health  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2839","authenticated-orcid":false,"given":"Holger","family":"Moch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"BexA AlbigesL BedkeJet\u00a0al.EAU guidelines on renal cell carcinoma: european association of urology.2025.https:\/\/uroweb.org\/guidelines\/renal\u2010cell\u2010carcinoma."},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","unstructured":"CampbellS UzzoRG AllafMEet\u00a0al.Renal mass and localized renal cancer: evaluation management and follow\u2010up: aua guideline: american urological association.2021.https:\/\/www.auanet.org\/guidelines\u2010and\u2010quality\/guidelines\/renal\u2010mass\u2010and\u2010localized\u2010renal\u2010cancer\u2010evaluation\u2010management\u2010and\u2010follow\u2010up.","DOI":"10.1097\/JU.0000000000001911"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13735"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000341"},{"key":"e_1_2_14_6_1","volume-title":"WHO classification of tumors of the urinary system and male genital organs","author":"Moch H","year":"2016"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318299f0fb"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.01.005"},{"key":"e_1_2_14_9_1","volume-title":"Renal epithelial neoplasms histopathology reporting guide","author":"Williamson S","year":"2025"},{"key":"e_1_2_14_10_1","unstructured":"MuruganPA LannaRW HarikLRet\u00a0al.Protocol for the examination of resection specimens from patients with renal cell carcinoma: college of american pathologists.2025.https:\/\/www.cap.org\/protocols\u2010and\u2010guidelines\/cancer\u2010reporting\u2010tools\/cancer\u2010protocol\u2010templates."},{"key":"e_1_2_14_11_1","volume-title":"WHO classification of Tumours. 5th edition. Urinary and male genital Tumours","year":"2022"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1949.tb10761.x"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)66257-8"},{"key":"e_1_2_14_14_1","first-page":"303","article-title":"Pathology and prognosis in renal tumors","volume":"130","author":"Mathisen W","year":"1965","journal-title":"Acta Chir. Scand."},{"key":"e_1_2_14_15_1","first-page":"1","article-title":"Renal adenocarcinoma; morphology\u2010\u2010grading of malignancy\u2013prognosis. A study of 197 cases","volume":"346","author":"Arner O","year":"1965","journal-title":"Acta Chir. Scand. Suppl."},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000472001"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)56521-0"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(80)90136-X"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)54359-1"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19830901)52:5<899::AID-CNCR2820520526>3.0.CO;2-#"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)62543-6"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1971)28:5<1165::AID-CNCR2820280513>3.0.CO;2-G"},{"key":"e_1_2_14_23_1","first-page":"49","article-title":"Grading of human renal adenocarcinoma","volume":"12","author":"Syrjanen K","year":"1978","journal-title":"Scand. J. Urol. Nephrol."},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)54948-4"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198210000-00007"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000472673"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/00313028709066560"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000471633"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.2000.00132.x"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1309\/VLV6-BRTR-HY5B-H485"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13311"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000209833.69972.2b"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318220697f"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318270f71c"},{"key":"e_1_2_14_35_1","first-page":"1139","article-title":"Verification of the International Society of Urological Pathology recommendations in Japanese patients with clear cell renal cell carcinoma","volume":"52","author":"Kim H","year":"2018","journal-title":"Int. J. Oncol."},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau-20-799"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000690"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001455"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-020-00716-0"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.07.001"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.08.006"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2021.12.006"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15042"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00990-9"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5532"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.06.067"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.06.006"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.052"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.12.001"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104431"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.21873\/cgp.20441"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.10.009"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.06.053"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/10668969231157317"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200103000-00001"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9419.1"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143381"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000004030"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2019.01.004"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23574"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.10.033"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1177\/10668969231189798"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqad096"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.155043"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001025"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.01.011"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200404000-00002"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002233"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2022.100640"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114350"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000801)89:3<604::AID-CNCR16>3.0.CO;2-Q"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01882"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2063"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13447"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2022.01.005"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12781"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16125"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-016-1314-z"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-025-05630-4"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16609"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2024.02.007"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2022.04.003"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2015.04.011"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2014.12.001"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2011.10785.x"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000251"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000787"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.01.002"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-007-0209-0"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20812"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20749"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.5858\/2003-127-0593-IAIVUT"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-021-01130-2"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00982-9"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.07.072"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.11.029"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2025.01.016"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.04.004"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-018-2373-9"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2017.09.002"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2025.102387"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.08.092"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000434"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-024-03865-x"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14700"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001802"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2018-205655"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.06.029"},{"key":"e_1_2_14_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2020.10.001"},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.02.128"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2011.10184.x"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13737"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2020.06.002"},{"key":"e_1_2_14_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100590"},{"key":"e_1_2_14_115_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPIMPE6ZFT8AME"},{"key":"e_1_2_14_116_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1447057"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70177","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70177","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:43:38Z","timestamp":1788857018000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":115,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/his.70177"],"URL":"https:\/\/doi.org\/10.1111\/his.70177","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2026-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}