Updates in Grading of Renal Cell Carcinomas Beyond Clear Cell Renal Cell Carcinoma and Papillary Renal Cell Carcinoma

Abstract

The World Health Organization (WHO) recommends grading of clear cell renal cell carcinoma (RCC) and papillary RCC using the WHO/International Society of Urological Pathology (ISUP) grade, which is primarily based on nuclear features. As the spectrum of RCC continues to evolve, with more recently described subtypes in the past decade, literature evidence on grading these subtypes is limited or not available for some tumor types. Herein, we outline a pragmatic approach to the topic of grading RCC, dividing the contemporarily described RCC subtypes into 7 categories based on the potential clinical applicability of grading as a useful prognostic parameter: (1) RCC subtypes that are reasonably validated and recommended for WHO/ISUP grading; (2) RCC subtypes where WHO/ISUP is not applicable; (3) RCC subtypes where WHO/ISUP grading is potentially clinically useful; (4) inherently aggressive RCC subtypes where histologic classification itself confers an aggressive biologic potential; (5) renal epithelial tumors where WHO/ISUP grading provides potentially misleading prognostic implication; (6) renal epithelial neoplasms where low WHO/ISUP grade features are a prerequisite for accurate histologic classification; and (7) renal epithelial neoplasms with no or limited data on grading or incomplete understanding of the biologic potential. Our aim in outlining this approach is 2-fold: (a) identify the gaps in understanding and application of grading in RCC subtypes so that researchers in the field may perform additional studies on the basis of which the important pathologic function of assignment of grade may be recommended to be performed as a meaningful exercise across a wider spectrum of RCC; and (b) to provide guidance in the interim to surgical pathologists in terms of providing clinically useful grading information in RCC based on currently available clinicopathologic information.

Understanding Factors that Influence Prognosis and Response to Therapy in Clear Cell Renal Cell Carcinoma

“…This grading system has been shown to correlate with cancer-specific survival in multivariate analyses 20 in both ccRCC and papillary RCC 21–23 . Tumor grading in other RCC subtypes has been addressed in a recent review 24 …”

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

“…Different subtypes of renal cell carcinoma exist. The clear cell entity (70-80%) is the most common type of RCC, directly followed by the papillary type (15%) [91,92]. Both are originated from the proximal tubule [33].…”

Cuproptosis patterns in papillary renal cell carcinoma are characterized by distinct tumor microenvironment infiltration landscapes

“…Currently, an increasing number of clinical investigations have been conducted on individuals with clear cell RCC and have identified many efficacious treatment targets, including VEGFR and mTOR ( Erlmeier et al, 2022 ; Labaki et al, 2022 ). Nevertheless, these strategies were less effective in PRCC patients, which may be due to the fact that PRCC carcinogenesis involves distinct genetic alterations and molecular pathways from clear cell RCC tumorigenesis ( Paner et al, 2022 ). As a result, new precise biomarkers and effective treatment techniques for PRCC are required.…”