Background/Objectives: Infiltrative renal masses, characterized by ill-defined margins and parenchymal invasion without forming a discrete mass, present a diagnostic challenge, particularly in patients without a prior history of malignancy. Differentiating among the most common malignant etiologies—renal cell carcinoma (RCC), urothelial carcinoma (UC), and lymphoma—is essential for guiding appropriate treatment. This study aimed to evaluate whether specific computed tomography (CT) features can assist in the differential diagnosis of these lesions. Methods: A retrospective review was conducted on 68 patients with infiltrative renal masses presented at a tertiary hospital’s oncologic urology committee between 2018 and 2022. Patients with prior malignancy or signs of infection were excluded. All cases underwent contrast-enhanced CT within three months of diagnosis and had histopathological confirmation. Imaging features such as necrosis, collecting system involvement, lymphadenopathy, and others were assessed and statistically analyzed. Results: RCC was the most frequent diagnosis (68%), followed by UC (18%) and lymphoma (7.4%). Significant differences were observed in imaging features: necrosis was more common in RCC (87%) than in UC (25%) and lymphoma (20%), p < 0.001; collecting system involvement was universal in UC (100%) and less common in RCC (65%) and lymphoma (40%), p = 0.009; and lymphadenopathy was more frequent in lymphoma (80%) than in UC (67%) and RCC (35%), p = 0.038. Tumor size also varied significantly, with lymphomas presenting the largest median size (11 cm), followed by RCCs (8.2 cm) and UCs (5 cm), p < 0.001. Conclusions: CT imaging features, particularly necrosis, collecting system involvement, and lymphadenopathy, can aid in distinguishing among RCC, UC, and lymphoma in patients with infiltrative renal masses and no prior cancer history. These findings may support more accurate diagnoses and inform tailored therapeutic strategies.

Renal cell carcinoma encompasses a heterogeneous group of kidney tumors with wide variations in biological behavior, histologic subtype, and clinical aggressiveness. Accurate preoperative characterization is essential for management; however, it remains challenging due to overlapping imaging features and tumor complexity. CT is the most widely used imaging technique for renal mass evaluation, providing broad availability, high spatial resolution, and multiphasic acquisition capabilities. However, its ability to distinguish histologic subtypes and predict tumor aggressiveness remains limited. This review provides an updated overview of renal cell carcinoma epidemiology and evidence supporting CT as an essential imaging modality. It outlines key radiologic features of main histologic subtypes, highlights markers of aggressive behavior, and discusses the relationship between CT findings and the International Society of Urological Pathology (ISUP) grading system. We explore radiomics, summarizing its methodological foundations and applications in characterizing solid renal masses, emphasizing the need for multicenter studies and standardized radiomic workflows to develop accurate, reproducible tools for improving diagnostic accuracy and risk stratification for renal cell carcinoma.

Renal cell carcinoma encompasses a heterogeneous group of kidney tumors with wide variations in biological behavior, histologic subtype, and clinical aggressiveness. Accurate preoperative characterization is essential for management, yet remains challenging because benign, indolent, and aggressive lesions often show overlapping imaging features. CT is the most widely used modality for renal mass evaluation, offering broad availability, high spatial resolution, and multiphasic acquisition. This comprehensive narrative review summarizes current evidence on CT-based characterization of renal cell carcinoma, radiologic–pathologic correlation, imaging markers of tumor aggressiveness, renal mass biopsy, and radiomics. Radiomics and other quantitative imaging approaches may complement conventional imaging by capturing tumor heterogeneity and biologically relevant features; however, most studies remain retrospective, single-center, and methodologically heterogeneous. Multicenter validation, standardized acquisition and segmentation, transparent reporting, and demonstration of added clinical value are required before these methods can be implemented in routine care.