Abstract：
The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.
摘要：
2022年国际泌尿外科病理学会（ISUP）关于泌尿系膀胱癌的共识会议第2工作组的任务是为混合等级的非浸润性尿路上皮癌的分级应用提供循证建议。浸润性尿路上皮癌，包括亚型（变异）和分化，和纯的非尿路上皮癌。研究表明，以局灶性高级别成分为主的低级别非侵袭性乳头状尿路上皮癌在低级别和高级别肿瘤之间具有中等结果。然而,对于如何定义重点高级别部分,没有达成共识.到2004年世卫组织分级，绝大多数固有层浸润性（T1）尿路上皮癌是高级别，和罕见的浸润性低度肿瘤显示只有有限的表面侵犯。而到1973年世卫组织分级，绝大多数T1期尿路上皮癌为G2和G3,根据肿瘤分级在结局上显示出显著差异.如果T1肿瘤应由2004年WHO系统或1973年WHO系统分级，则未达成共识。由于对诊断不足和潜在治疗不足的漏报的担忧，参与者一致建议应报告尿路上皮癌亚型的存在和不同的分化.人们一致认为，这些亚型和不同分化的程度也应该在活检中记录下来。经尿道电切术,和膀胱切除术标本。任何不同的亚型和不同的分化应该在没有阈值截止的情况下进行诊断。每种类型都应该在具有组合形态的肿瘤中进行列举。与会者一致认为，根据2004年世卫组织分级系统，所有亚型和不同的区别都应被视为高等级。然而,参与者强烈承认,就行为而言,亚型和差异不应被视为同质群体.因此，未来的研究应集中于个体亚型和不同的分化,而不是将这些不同的实体归入一个临床病理组中.同样，临床建议应注意亚型的潜在异质性以及行为和治疗反应方面的差异.人们一致认为，浸润性纯鳞状细胞癌和纯膀胱腺癌应根据分化程度进行分级。总之,国际泌尿外科病理学学会第2工作组会议的摘要解决了一些超出其传统应用范围的分级问题，包括混合等级和侵入性成分的乳头状尿路上皮癌。还详细介绍了亚型和差异的报告，承认他们在风险分层中的作用。该报告可以作为最佳实践的指南，并可以为这些肿瘤的预后提供未来的研究和建议。
