Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility

Abstract

The clinical management of tumor patients is often strongly influenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Biological significance of TERT promoter mutation in papillary urothelial neoplasm of low malignant potential

“…Moreover, and probably more importantly, the actual cut-off points of histological classification are subject to interobserver variation. 25,26 In fact, all the low-grade NIPUC cases in our study were diagnosed originally as PUNLMP or even inverted papilloma. Although our study found no TERT promoter mutation in any case of inverted papilloma, Cheng et al reported TERT promoter mutations in 15% (four of 26) cases of inverted papillomas.…”

“…In our study, the prognostic value of TERT promoter mutations fell to an equivocal level if PUNLMP and low‐grade NIPUC cases were mixed ( P = 0.052). Moreover, and probably more importantly, the actual cut‐off points of histological classification are subject to interobserver variation . In fact, all the low‐grade NIPUC cases in our study were diagnosed originally as PUNLMP or even inverted papilloma.…”

Oncological predictive value of the 2004 World Health Organisation grading classification in primary T1 non‐muscle‐invasive bladder cancer. A step forward or back?

“…Furthermore, as the tumour grade of all patients with NMIBC was always assigned to a single expert uro-pathologist, the interobserver discrepancy for grading attribution could not be addressed. It should be recognised that, although a single-pathologist report can be seen as an advantage with respect to the continuity of the process over the years and reflecting many clinical routine contexts, it may also be considered the major criticism of the present results [21][22][23][24]. The absence in the multivariable analysis of histological microstaging and lymphovascular invasion (available for ∼50 and 30% of cases, respectively) might be considered as an additional limiting factor for results interpretation [25][26][27].…”

Comparison of pathological staging and grading of urothelial bladder carcinoma in post-transurethral resection and post-radical cystectomy specimens

“…In a recent study published by May, the agreement on grade among four pathologists was 38-73% when using the 1973 WHO classification and 72-83% when using the 2004 WHO/ ISUP classification [36]. Analogous values in previously published studies were in the ranges of 17-80% and 33-95%, respectively [30,[37][38][39][40][41][42][43][44][45]. These data are presented in Table V.…”