Clinicopathologic Significance of Nuclear Grooves and Inclusions in Renal Cell Carcinoma: Image Database Construction and Quantitative Scoring

Abstract

Nuclear grooves and inclusions are major features of cancer. However, the nuclear irregularities in renal cell carcinoma (RCC) have not yet been well characterized. To determine the clinicopathologic significance of nuclear grooves and inclusions in RCC. The frequencies or scores of nuclear grooves and inclusions were compared with the histologic subtype, nuclear grade, and TNM stage, as well as overall survival of RCC patients. For objective counting of nuclear irregularities, a relational image database was constructed and used for quantitative assessment. Nuclear grooves and inclusions were seen in 96% and 65% of 110 RCC cases, respectively. The intranuclear inclusions were found more frequently in chromophobe and papillary types than in clear cell carcinoma (P < .001). The nuclear scores, the sum of grooves or inclusions per 5000 tumor cells, were highly related to the histologic subtype (P < .001). Clear cell RCCs with high inclusion scores (2 or more) were correlated with poorer overall survival in comparison to clear cell carcinomas with low inclusion scores (P = .04). The groove scores were highly associated with Fuhrman grade (P = .003) but not with overall survival of clear cell RCC patients (P = .65). In multivariate analysis, higher inclusion scores and advanced tumor stages (III/IV) were correlated with worse outcomes of clear cell RCC. Nuclear grooves and inclusions are histologic components of RCCs, especially chromophobe and papillary carcinomas. Furthermore, nuclear inclusions might be an independent prognostic factor for clear cell RCC.