Background
Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior.
Objective
To comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes.
Design, setting, and participants
We identified 89 CCPRCC patients and compared their clinicopathologic features with 1120 localized clear cell renal cell carcinoma (ccRCC) and 129 type 1 papillary renal cell carcinoma (pRCC) patients.
Outcome measurements and statistical analysis
Nonparametric statistical testing was used to compare relevant features between tumor types. Overall, cancer-specific survival (CSS) and metastasis-free survival estimates were calculated from initial diagnosis using the Kaplan-Meier method. Patients with ipsilateral multifocal disease were explored further. A subset of CCPRCC tumors underwent genomic analysis and were compared with other RCC subtypes.
Results and limitations
A higher proportion of female (45% vs 32%) and African-American (19% vs 3%) patients were observed in the CCPRCC cohort than in the ccRCC and pRCC cohorts. CCPRCC tumors also had increased odds of presenting with additional ipsilateral masses (odds ratio [OR]: 4.41 [confidence interval {CI}: 2.34, 8.15], p < 0.001) and bilateral disease (OR: 4.80 [CI: 2.40, 9.59], p < 0.001) compared with ccRCC tumors. On molecular analysis, CCPRCC tumors showed fewer somatic aberrations and a greater degree of mitochondrial DNA depletion. In multifocal CCPRCC tumors, histologic concordance among the different renal cell carcinoma masses was estimated at 44% (7/16), and none of the individuals presenting exclusively with CCPRCC tumors developed metastatic disease after 5 yr. In contrast, multifocal tumors with CCPRCC and other nonconcordant histologies were more likely to experience adverse outcomes (CSS, log rank p = 0.034).
Conclusions
CCPRCC is characterized by distinct molecular and epidemiologic features that could be used to refine current diagnostic approaches. Although their clinical course is generally indolent, multifocal CCPRCC tumors represent a unique diagnostic challenge. In this context, single-mass biopsies could miss concomitant aggressive disease, with a potential negative impact on patient outcomes. Furthermore, high discordance rates in multifocal CCPRCC tumors have important clinical implications in management.
Clear cell papillary renal cell carcinoma (CCPRCC), a relatively new tumor entity, accounts for 2-4% of renal cortical tumors. In this study, we sought to comprehensively characterize the clinicopathologic and molecular features of CCPRCC and compare them to more common kidney cancer subtypes.
In this series of 89 patients with CCPRCC tumors, we report distinct clinicopathologic and molecular features, and a reassuringly excellent prognosis. We found a balanced gender distribution, a higher rate in African-Americans (19%), and a high rate of multifocality (25%), which was often histologically discordant (56%). No patients died of the disease nor were there any documented distant metastases. Genomically, CCPRCC tumors are remarkably “boring” with no recurrent copy number events or mutations, and have significantly lower mitochondrial DNA content compared to other RCC subtypes. Is CCPRCC a benign entity given the lack of metastases and relatively bland genome? Time will tell as we characterize larger data sets with longer follow-up periods.
A major diagnostic challenge is the overlapping morphologic features of CCPRCC with other potentially aggressive RCC entities. This complicates a solely biopsy-based diagnosis, and therefore in the context of limited tumor sampling, a combination of both morphologic and immunohistochemical criteria should always be used for diagnosis.
Furthermore, high rates of multifocality and histologic discordance in CCPRCC tumors add additional complexity to the management of this disease. Multifocal CCPRCC diagnoses based on single-mass biopsy should warrant further caution from surgeons. These patients should be closely followed, and new tumors should not be assumed to be of the same histology. Tissue sampling of at least two distinct masses may help drive clinical management decisions.