Prognostic value and reproducibility of different microscopic characteristics in the WHO grading systems for pTa and pT1 urinary bladder urothelial carcinomas

Vebjørn Kvikstad,Hans Espeland,Einar Gudlaugsson,Emiel A M Janssen,Ingvild Dalen,Ok Målfrid Mangrud,Jan P A Baak

doi:10.1186/s13000-019-0868-3

Abstract

BackgroundEuropean treatment guidelines for pTa and pT1 urinary bladder urothelial carcinoma depend highly on stage and WHO-grade. Both the WHO73 and the WHO04 grading systems show some intra- and interobserver variability. The current pilot study investigates which histopathological features are especially sensitive for this undesired lack of reproducibility and the influence on prognostic value.MethodsThirty-eight cases of primary non-muscle invasive urothelial carcinomas, including thirteen cases with stage progression, were reviewed by three pathologists. Thirteen microscopic features were extracted from pathology textbooks and evaluated separately. Reproducibility was measured using Gwet’s agreement coefficients. Prognostic ability regarding progression was estimated by the area under curve (AUC) of the receiver operating characteristics (ROC) function.ResultsThe best reproducible features (Gwet’s agreement coefficient above 0.60) were papillary architecture, nuclear polarity, cellular maturation, nuclear enlargement and giant nuclei. Nucleoli was the strongest prognostic feature, and the only feature with an AUC above 0.70 for both grading systems, but reproducibility was not among the strongest. Nuclear polarity also had prognostic value with an AUC of 0.70 and 0.67 for the WHO73 and WHO04, respectively. The other features did not have significant prognostic value.ConclusionsThe reproducibility of the histopathological features of the different WHO grading systems varied considerably. Of all the features evaluated, only nuclear polarity was both prognostic and significantly reproducible. Further validation studies are needed on these features to improve grading of urothelial carcinomas.

Highlights

European treatment guidelines for pTa and pT1 urinary bladder urothelial carcinoma depend highly on stage and World Health Organization (WHO)-grade
Urothelial carcinoma accounts for about 90% of bladder cancers in industrialized countries
In 1973 the World Health Organization (WHO) introduced a classification system, in which papillary carcinomas were divided into three groups; grades 1, 2 and 3 (WHO73)

Summary

Introduction

European treatment guidelines for pTa and pT1 urinary bladder urothelial carcinoma depend highly on stage and WHO-grade Both the WHO73 and the WHO04 grading systems show some intra- and interobserver variability. Urothelial carcinoma accounts for about 90% of bladder cancers in industrialized countries [3], and 70–80% of these are non-muscle-invasive bladder cancers (NMIBC), pTa, pT1 or pTis, on first diagnosis Among these 50–70% will recur, while only 15–25% will progress to a higher stage [4]. A new classification system was Kvikstad et al Diagnostic Pathology (2019) 14:90 introduced in the 2004 WHO Classification of tumours of the urinary system (“blue book”), following an International Society of Urological Pathology (ISUP) consensus conference in 1998 (WHO04) This grading system is maintained in the 4th.edition, 2016, of the WHO blue book. In a recent review Soukup et al [12] conclude, on behalf of the European Association of Urology (EAU), that the “Current grading classifications in NMIBC are suboptimal”, both with regards to reproducibility (poor to fair) and with regards to prognostication

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