Renal cell carcinoma (RCC) is most commonly diagnosed as an incidental small renal mass (SRM, ≤4cm \[cT1a\]). The incidence of RCC has markedly increased in the last few decades due to the widespread utilization of cross-sectional imaging. The increased detection of renal masses has resulted in an accompanying increase in the number of surgeries and ablations performed for a mass suspected of being a cancer. However, despite aggressive treatment of SRMs over the last few decades, there has not been a substantial decrease in kidney cancer-specific mortality suggesting an over-treatment effect - i.e., many patients may not benefit from extirpative or ablative treatment. Furthermore, approximately 20% of small (≤4 cm) solid renal masses are benign neoplasms, mostly oncocytoma and angiomyolipoma. Benign masses generally do no harm and can be ignored or followed up as they do not limit a patient's lifespan. Even when malignant, small solid masses are frequently indolent with low rates of local disease progression or metastasis. The proportion of benign diagnoses and indolent RCCs is higher among solid masses smaller than 2 cm. Although percutaneous renal mass biopsy can offer a definitive diagnosis, it is not feasible in every patient, and carries a high non-diagnostic rate (14-19%), has low negative predictive value (63%) and underestimates tumor grade. For these reasons, combined with a desire to identify aggressive renal masses with increased risk of progression or metastasis promptly and decrease patient morbidity and health-care costs related to unnecessary treatments, there is a need for developing imaging techniques that better characterize renal masses. In addition to differentiating benign from malignant disease, distinction between indolent malignant renal masses from aggressive neoplasms is important for decision making, with the later typically requiring prompt intervention. In contrast, active surveillance may be favored for patients with indolent malignancies, particularly for those with competing comorbidities and limited life expectancy. Unfortunately, the lack of reliable predictors of oncologic behavior have also limited the wide clinical adoption of active surveillance as a management strategy. Aggressive renal masses are classified by the presence of any high grade (HG, International Society of Urogenital Pathology (ISUP) grade 3 or 4 out of 4) features on histology or the presence of sarcomatoid and rhabdoid features, coagulative necrosis.

Alternatively, a diagnosis of the histologic subtype of RCC may assist in management decisions. For example, clear cell renal cell carcinoma (ccRCC) is the most common histology and metastasizing tumor. The clear cell likelihood score (ccLS) is a 5-tier system developed at the University of Texas Southwestern Medical Center (UTSW) to predict the likelihood of a solid renal mass to represent a clear cell renal cell carcinoma. In a multicenter, retrospective study, the reported pooled sensitivity, specificity, and positive predictive value for ccRCCs using a ccLS of 4 or 5 were 75% (95% CI: 68, 81), 78% (95% CI: 72, 84), and 76% (95 CI: 69, 81), respectively. The negative predictive value for a ccLS of 1 or 2 was 88% (95% CI: 81,93).

Patients referred for MRI of an indeterminate renal mass will be eligible for this study. PET/MRI in this study will be performed as a replacement of the standard-of-care MRI examination. Thus, the PET component of the PET/MR examination is a research procedure. Patients will be screened for any contraindication of MRI (e.g., unsafe indwelling device) as it is routinely done in the Department of Radiology for clinical MRI examinations. Patients will be administered with 12 mCi of FDG I.V, which is consistent with the FDG radiation dose patients receive for FDG PET/CT examinations performed as standard of care. Patients will receive 20 mg of furosemide 60 min after administration of FDG. The patient will be asked to empty their bladder as much as needed for the following 60 min. The patient will then be placed on the PET/MRI table 60 min after administration of FDG for a 10 min quick PET/MR acquisition the abdomen. The patient will be removed from the scanner and asked to empty their bladder as needed. The patient will be placed on the MRI scanner again 120 min after the administration of FDG to complete their standard of care MRI. A gadolinium-enhanced MRI of the kidneys will be obtained using the standard clinical protocol for MRI of renal masses at UTSW. An extracellular gadolinium-based contrast agent will be administered during the MRI and is not part of the study procedures. PET data of the kidneys will be acquired simultaneously during the MRI examination as part of the study procedures. UTSW standard operating procedures will be followed with regards to fasting and blood glucose measurements for patients undergoing FDG PET imaging in this study. PET images will be coregistered to MRI data and mean and maximum standardized uptake value in the renal mass will be calculated. MRI images will be interpreted using the standard clinical report and a ccLS will be provided. For patients undergoing standard of care biopsy, an extra core will be obtained for future research from participants who opt-in to have extra core collected when they sign informed consent form. If the renal mass is resected surgically, a piece of discarded tissue will be collected for similar correlative studies. The extra core or the discarded tissue will be used for histology and metabolomics analysis to understand the correlation of FDG uptake and tumor metabolism.