Grading of Clear Cell Renal Cell Carcinoma Should be Based on Nucleolar Prominence

Abstract

Fuhrman grading of renal cell carcinoma focuses on features of nuclear size, nuclear shape, and nucleolar prominence. Despite the reported widespread usage of Fuhrman grading in clinical studies, there is debate as to the prognostic significance and reproducibility of its criteria. It has been noted that many pathologists rely on assessment of nucleolar prominence alone when grading renal cell carcinoma; however, the validity of this remains unconfirmed. This study was undertaken to determine the relationship of the 3 morphologic components of the Fuhrman grading system with one another and to determine which, if any of these, can be correlated with outcome for clear cell renal cell carcinoma. One hundred twenty-one organ-confined clear cell renal cell carcinomas were examined in this study. Parameters of nuclear size (area, major axis, perimeter) and nuclear shape (shape factor, nuclear compactness) were assessed by image analysis, whereas nucleolar prominence was assigned (grades 1 to 3) using the criteria of Fuhrman. On the basis of the predominant grade present, there were 17 nucleolar grade 1, 90 nucleolar grade 2, and 14 nucleolar grade 3 tumors. When the high-power field in each tumor with the worst nucleolar grade was assessed, there was 1 nucleolar grade 1, 68 nucleolar grade 2, and 52 nucleolar grade 3 tumors. Predominant and worst nucleolar grade correlated with all measures of nuclear size, but not nuclear shape. Worst nucleolar grade and all parameters of nuclear size were significantly associated with outcome. On multivariate analysis, worst nucleolar grade retained a significant association with survival when modeled with nuclear area. Neither worst nucleolar grade nor major nuclear axis/nuclear perimeter was significantly associated with survival when modeled together. In this study, we have shown that worst nucleolar grade and nuclear size are of prognostic significance for clear cell renal cell carcinoma. We have further shown the association of worst nucleolar grade with outcome to be independent of nuclear area, whereas it is a dependent variable when tested against other parameters of nuclear size. These findings indicate that worst nucleolar grading alone is a valid grading parameter for clear cell renal cell carcinoma.

Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome

“…They concluded that nucleolar prominence alone held significance for stratifying these tumors [11]. A follow-up study also revealed that nucleolar grade was predictive of survival for clear cell RCC on multivariate analysis, and that alone was a valid grading parameter [35]. These studies suggested that nucleolar prominence independently was a suitable grading system for both clear cell RCC and PRCC [10].…”

Clinicopathologic Patterns of Adult Renal Tumors in Pakistan

“…It was suggested that nucleolar grading alone is a valid grading parameter of CCRCC (Delahunt et al, 2011) et al, 2007). Multiple systems are used to grade RCC of which Furhman's grade is most widely used (Rioux et al, 2007).…”

WHO-ISUP-Graduierungssystem für Nierenkarzinome

“…Inwieweit diese Parameter voneinander abhängig sind, wurde bisher noch nicht untersucht. In der Praxis ist jedoch Tatsache, dass die meisten Pathologen beim Fuhrman-Grading nahezu ausschließlich die Größe der Nukleolen beurteilen und die beiden anderen Parameter des Fuhrman-Systems (Kerngröße und Kernpolymorphie) weitgehend ignorieren [15]. Einzelne Studien haben für klarzellige Nierenkarzinome gezeigt, dass die Kernform nicht mit der Prognose korreliert und bei papillären Nierenzellkarzinomen ist weder die Kerngröße noch die Kernform von prognostischer Bedeutung [42].…”