International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas

Gladell P. Paner, Ashish Kamat, George J. Netto, Hemamali Samaratunga, Murali Varma, Lukas Bubendorf, Theodorus H. Van Der Kwast, Liang Cheng, Adebowale Adeniran, Hikmat Al-Ahimadie, Fernando Algaba, Yves Allory Selina Bhattarai, Peter Black, David Berman, Simone Bertz, Lukas Bubendorf, Birgitte Carlsen, Rita Carvalho, Obinna Chijioke, Yong Mee ChoEva Comperat, Isabela Di Cunha, Julien Dagher, Isabella De Cunha, Brett Delahunt, Michelle Downes, Thomas Flaig, Achim Fleischmann, Cosmin Florescu, Jacqueline Fontugne, Vera Genitsch, Guro Horni Gløersen, Michael Von Gunten, Rainer Grobholz, Donna Hansel, Arndt Hartmann, Loren Herrera Hernandez, Mattias Hogland, Jiaoti Huang, Brad Jensen, Kenneth Iczkowski, Rafael Jimenez, Bojana Jovanovic, Ashish Kamat, Jens Koellermann, Trevor Levin, Fredrik Liedberg, Antonio Lopez-Beltran, Anand C. Loya, Marianne Lyngra, Teresa McHale, Khadidja Mokeddem, George Netto, Maya Nourieh, Declan O'Rourke, Irina Alexandra Ostahi, Gladell Paner, Maria M. Picken, Flavia Guzman Pineda, Camelia Radulescu Maria Raspollini, Henning Reis, Shi Ruoyu, Hemamali Samaratunga, Remi Semba, Nigam Shah, Steven Shen, Steven Smith, Tovia Smith, John Srigley, Sueli Suzigan, Nicole Swarbrick, Ildiko Szalay, Inger Talleraas, Jean Christophe Tille, Marieta Toma, Isabel Trias, Toyonori Tsuzuki, Theodorus Van Der Kwast, Bas Van Rhijn, Murali Varma, Sofie Verbeke, Sangeeta Verma, Tatjana Vlajnic, Ljiljana Vlatkovic, Anne Warren, Joshua Warrick, Sean Williamson, Sara Wobker, Clifton Woods, Chen Yang, Ghilsuk Yoon

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E11-E23
JournalAmerican Journal of Surgical Pathology
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2024

Keywords

  • Bladder
  • ISUP
  • WHO
  • cancer
  • divergent
  • grade
  • invasion
  • mixed
  • reporting
  • subtypes
  • variants

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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