Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

Purpose: The diagnostic differential for CD117/KIT(+) oncocytic renal tumor biopsies is limited to benign renal oncocytoma versus chromophobe renal cell carcinoma (ChRCC); however, further differentiation is often challenging and requires surgical resection. We investigated clinical variables that might improve preoperative differentiation of CD117(+) renal oncocytoma versus ChRCC to avoid the need for benign tumor resection.Experimental Design: A total of 124 nephrectomy patients from a single institute with 133 renal oncocytoma or ChRCC tumors were studied. Patients from 2003 to 2012 comprised a retrospective cohort to identify clinical/radiographic variables associated with renal oncocytoma versus ChRCC. Prospective validation was performed among consecutive renal oncocytoma/ChRCC tumors resected from 2013 to 2017.Results: Tumor size and younger age were associated with ChRCC, and multifocality with renal oncocytoma; however, the most reliable variable for ChRCC versus renal oncocytoma differentiation was the tumor:cortex peak early-phase enhancement ratio (PEER) using multiphase CT. Among 54 PEER-evaluable tumors in the retrospective cohort [19 CD117(+), 13 CD117(-), 22 CD117-untested], PEER classified each correctly as renal oncocytoma (PEER >0.50) or ChRCC (PEER ≤0.50), except for four misclassified CD117(-) ChRCC variants. Prospective study of PEER confirmed 100% accuracy of renal oncocytoma/ChRCC classification among 22/22 additional CD117(+) tumors. Prospective interobserver reproducibility was excellent for PEER scoring (intraclass correlation coefficient, ICC = 0.97) and perfect for renal oncocytoma/ChRCC assignment (ICC = 1.0).Conclusions: In the largest clinical comparison of renal oncocytoma versus ChRCC to our knowledge, we identified and prospectively validated a reproducible radiographic measure that differentiates CD117(+) renal oncocytoma from ChRCC with potentially 100% accuracy. PEER may allow reliable biopsy-based diagnosis of CD117(+) renal oncocytoma, avoiding the need for diagnostic nephrectomy. Clin Cancer Res; 24(16); 3898-907. ©2018 AACR.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.