AUTHOR=Alkan Gökhan Veli , Doğan Kutsal , Türk Alkan Meltem , Önder Evrim 
  
TITLE=Prognosis and tumor grading in bladder urothelial carcinomas with intratumoral grade heterogeneity
  
JOURNAL=Pathology and Oncology Research
  
VOLUME=Volume 32 - 2026
  
YEAR=2026
  
URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2026.1612553
  
DOI=10.3389/pore.2026.1612553
  
ISSN=1532-2807
  
ABSTRACT=AimsGrade heterogeneity is one of the most debated issues in the grading of urothelial carcinomas. The 2022 WHO classification states that approximately one-third of urothelial carcinomas exhibit grade heterogeneity and suggests that the presence of ≥5% high-grade component may justify classification as high-grade. Nevertheless, the need for further evidence was also emphasized. This study aimed to evaluate the prognostic impact of the high-grade component in urothelial carcinomas with grade heterogeneity and to determine a threshold value for high-grade proportion that is clinically meaningful for grading.MethodsThis retrospective study included 180 cases of non-muscle-invasive urothelial carcinoma with grade heterogeneity, diagnosed between January 2019 and August 2022 on TUR specimens, with available clinical data. Recurrence and survival time were assessed. Cases with >90% high-grade component were excluded.ResultsRecurrence was observed in 26.7% of cases. The two-year survival rate was 73.3%. While no significant association was found between recurrence and the proportion of high-grade component, survival time significantly decreased as the proportion of high-grade component increased. ROC curve analysis identified 27.5% as the cut-off value associated with adverse prognosis.ConclusionIn non-muscle-invasive urothelial carcinomas, the proportion of high-grade component showed a strong association with survival. Together with literature findings, our results suggest that a threshold higher than 5% may be more appropriate for assigning tumors to the high-grade category. Nonetheless, risk stratification incorporating tumor size and extent remains essential for prognostic evaluation.