The expansion of cross-sectional imaging has led to a rise in the incidentally detected renal masses, including renal cell carcinomas (RCC). Though most incidentally detected renal masses are cysts, a clinical challenge is distinguishing cystic (often proteinaceous or hemorrhagic) from solid lesions, particularly when only a single phase examination is available. Spectral CT has the potential to offer advantages across different clinical applications in RCC. It has direct protocol implications, reducing the number of phases needed in CT urography or renal CT protocols, thereby lowering radiation dose while maintaining accuracy and cost-effectiveness. In addition, energy- and material-specific information can be extracted from a single data set, including quantitative data often regarded as surrogates of functional information (e.g., perfusion) that could be used to characterize renal lesions. Spectral CT imaging enables accurate distinction between cystic and solid renal masses. It could be a useful adjunct tool that improves characterization and monitoring, but it doesn't yet replace biopsy or histology, especially for subtype and grading, and may play an important role in post-treatment follow-up, assessment of therapy response, and differentiation of metastasis. Finally, PCCT offers the added advantages of improved spatial resolution and reduced contrast dose, image noise, and artifacts. PCCT may also enable new applications, such as K-edge imaging. The purpose of this article is to provide the reader with a summary of the technique's physics and its potential advantages, including both current and emerging applications in RCC.

Cystic nephroma (CN) is an uncommon benign pediatric renal neoplasm composed of multiloculated cysts separated by fibrous septa, lacking solid or blastemal elements. It occurs primarily in toddlers, often presenting as an asymptomatic abdominal mass. CN lies at the benign end of the spectrum that includes cystic partially differentiated nephroblastoma (CPDN) and Wilms tumor. We report a case of pediatric CN with detailed imaging and clinical correlation to highlight its distinguishing features. In this report, we present a case of a one-year-old boy who presented with a three-month history of a left-sided abdominal mass. Ultrasound showed a well-circumscribed multicystic lesion at the left kidney's lower pole, composed of anechoic loculi with thin septa (no solid component or vascularity). Contrast-enhanced CT confirmed a large (≈11 × 9 × 8 cm) encapsulated multiloculated cystic mass arising from the left kidney's lower pole, with enhancing thin septa and herniation of cysts into the pelvicalyceal system; no enhancing nodules or calcifications were seen. The patient underwent left nephroureterectomy; grossly, the specimen showed numerous clear-fluid cysts separated by fibrous septa. Microscopically, cysts were lined by flattened-cuboidal epithelium with focal hobnail change, and fibrous septa contained only mature stroma and inflammation, with no blastema or immature elements - consistent with CN (resection margins and sampled lymph nodes were free of tumor).

Papillary architecture is rare in FLCN-mutated renal epithelial neoplasms in Birt-Hogg-Dubé syndrome. We report a papillary-predominant FLCN-mutated renal epithelial neoplasm in a 79-year-old woman with known Birt-Hogg-Dubé syndrome and a pathogenic germline FLCN frameshift mutation, who presented with bilateral renal masses and underwent right partial nephrectomy. Gross examination revealed a 2.5 cm well-circumscribed yellow mass confined to the kidney (pT1a). Histologically, the tumor demonstrated predominantly papillary architecture with focal cystic change and rare nested oncocytic cells at the periphery. Fibrovascular cores were lined by oncocytic cells admixed with clear cells, the latter more prominent along the apical surface. Tumor cells showed round to oval nuclei with prominent nucleoli, focal coarse eosinophilic cytoplasmic granules, multifocal nuclear palisading, and rare multinucleated cells. The background renal parenchyma contained cysts lined by hobnail oncocytic cells with focal clear cell change. The tumor was positive for PAX8, AMACR, GPNMB, and cathepsin K, and negative for KIT, KRT7, and CA9, with diffuse weak-to-moderate TFE3 staining. The clinical history, morphology, and immunophenotype support a diagnosis of FLCN-mutated renal epithelial neoplasm with papillary features. This report highlights potential diagnostic pitfalls and the morphological heterogeneity of FLCN-mutated tumors.

Accurate delineation of kidney tumours in Computed Tomography (CT) is essential for downstream quantitative analysis and precision oncology that could enable personalised treatments, but manual segmentation is a specialised task, time-consuming and difficult to scale in routine practice. Automated 3D segmentation remains challenging in medical imaging, where images are large and dense volumes of data, making high-resolution processing with conventional dense convolutional neural networks computationally expensive, and often reliant on downsampling or patch-based inference. To overcome this problem, we propose a two-stage 3D segmentation methodology based on voxel sparsification and submanifold sparse convolutional networks (SSCNs). In Stage 1, a low-resolution sparse network identifies a region of interest (ROI); in Stage 2, a high-resolution sparse network performs refined segmentation within the cropped ROI. This design enables native 3D processing at high resolution while reducing CPU/GPU memory usage and inference time. We evaluate the method on the KiTS23 dataset of renal cancer CT scans using 5-fold cross-validation. Our method achieved Dice similarity coefficients of 95.8% for kidneys + masses, 85.7% for tumours + cysts, and 80.3% for tumours alone, with performance competitive with top KiTS23 approaches. In direct comparisons on the same cross-validation folds, the proposed sparse method achieves tumour + cyst and tumour-only Dice scores comparable to, and slightly higher than, a patch-based nnU-Net baseline, while consistently requiring less VRAM and shorter inference time across the tested hardware. Across the tested GPUs, our sparse model is markedly faster than both nnU-Net and the zero-shot zoom-out/zoom-in foundation model SegVol, which localises kidneys well but underperforms on small heterogeneous lesions. Compared to an equivalent dense implementation of the same architecture, the proposed sparse approach achieves up to a 60% reduction in inference time and up to a 75% reduction in VRAM usage across both CPU and the GPU configurations tested.

Nephronophthisis is an autosomal recessive ciliopathy and a major genetic cause of end-stage kidney disease in children and young adults. Although next-generation sequencing panels have improved diagnostic yield, some patients remain genetically unresolved, partly due to deep intronic variants that disrupt pre-mRNA splicing and are not captured by exon-focused approaches. We report a 13-year-old boy who presented with advanced kidney dysfunction, small renal cysts, and kidney histopathology consistent with nephronophthisis. Targeted gene panel sequencing failed to identify causative pathogenic variants beyond a missense variant of uncertain significance. Whole-genome sequencing subsequently revealed compound heterozygous variants in IFT172 (NM_015662.3): a missense variant (c.4696C > T, p.Arg1566Cys) and a deep intronic variant (c.4915-94A > G). In silico analysis predicted activation of cryptic splice sites leading to inclusion of an 86-bp pseudoexon, which was confirmed by a minigene splicing assay. These findings established a molecular diagnosis of IFT172-related nephronophthisis. To our knowledge, this is the first report demonstrating pseudoexon inclusion in IFT172, thereby expanding its mutational spectrum. Our case underscores the importance of evaluating deep intronic regions using whole-genome sequencing and functional validation in genetically unresolved nephronophthisis.

Disruption of PKD2 function causes polycystic kidney disease (PKD) and leads to the formation of cysts in the kidney in both mice and humans. PKD is progressive, initiating with the formation of tubule dilations that expand into large cysts, causing the destruction of renal parenchyma and loss of kidney function. The mechanisms initiating tubule dilation and expansion are uncertain. Tubule obstruction has been proposed as a factor contributing to cystogenesis. Here, we utilize a proximal tubule fluorescent dextran uptake assay to evaluate changes in tubule flow that occur during cyst initiation or expansion and functional decline. We did not observe overt signs of tubule obstruction during cyst initiation or expansion, even in larger cysts; however, the rate of tubule flow within individual nephrons was greatly diminished in cystic kidneys. Surprisingly, along with reduced tubule flow rate, we observe an increase in newly labelled dextran cells associated with disease in the Pkd2 mutants. These cells are spatially distinct from those absorbing the initial dextran and are detected in both cortical and medullary regions of mutant kidneys. Marker analysis indicated that the dextran[+] medullary cells were in the Loop of Henle and interstitial macrophages. These cells are not present in wild-type controls. This may be due to tubule or vasculature leakage and utilization of renal reserve capacity in mutants that become exhausted, associated with declining GFR as cysts expand.

Perinephric myxoid pseudotumor of fat (PMPF) is a very rare, benign perirenal mass that has been described in patients with advanced and inflammatory kidney disease. On imaging, PMPF can mimic benign and malignant lesions ranging from simple cysts to poorly differentiated malignant liposarcoma. Histologically, it consists of adipose cells, myxoid stroma, spindle cells and inflammatory cells, mainly lymphocytes. Herein, we report on our center's experience with PMPF in kidney transplant recipients with allograft loss presenting for re-transplant evaluation and provide a review of the existing literature. PMPF often presents as an incidental radiologic finding in end-stage kidney disease patients undergoing evaluation for re-transplantation. It may represent a localized reaction to renal parenchymal inflammation often caused by recurrent rejection, or chronic immunologic intolerance of previous allografts. PMPF is benign but should be differentiated from malignant entities such as well-differentiated liposarcoma.

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by germline mutations in the FLCN gene, characterized by cutaneous fibrofolliculomas, pulmonary cysts, and an increased risk of renal neoplasms. Parotid oncocytoma is an infrequently reported extracutaneous manifestation of the syndrome. A 30-year-old man with a prior history of testicular embryonal cell carcinoma presented with a right-sided neck mass. Workup of the parotid lesion ultimately led to a new diagnosis of BHD, confirmed by FLCN germline mutation testing. The patient underwent right parotidectomy, which was technically complex due to parapharyngeal extension and adherence to the facial nerve. Final pathology confirmed oncocytoma with clear cell features; all three lymph nodes were negative for metastatic carcinoma. The patient has remained without evidence of disease at over two years of postoperative follow-up. This case illustrates the diagnostic challenges posed by BHD-associated parotid oncocytoma, particularly when clear cell morphology raises concern for metastatic renal cell carcinoma or recurrent germ cell tumor. Clinicians should consider BHD in younger patients presenting with oncocytic parotid tumors, as recognition carries important implications for long-term renal and pulmonary surveillance.

Maturity-onset diabetes of the young type 5 (MODY5) is a rare autosomal-dominant monogenic diabetes caused by functional loss of the transcription factor, hepatocyte nuclear factor-1 beta (HNF1B). Although numerous HNF1B variants have been reported, the molecular mechanisms underlying the wide phenotypic variability-particularly among missense variants-remain incompletely understood. In this report, we describe a 12-year-old Japanese female with early-onset diabetes mellitus, pancreatic hypoplasia, and multiple renal cysts, harboring a novel de novo HNF1B missense variant (p.Met160Thr) located within the POU-specific domain. This early multisystem presentation highlights the clinical relevance of variants affecting this domain. Through in vitro analyses, including electrophoretic mobility shift assays, circular dichroism spectroscopy, and luciferase reporter assays, we demonstrate that the p.Met160Thr variant results in structural alterations, impaired DNA-binding stability, and markedly reduced transcriptional activity. Importantly, our data indicate that this variant acts via haploinsufficiency rather than a dominant-negative mechanism and disrupts normal HNF1A-mediated transcriptional function. These findings expand current understanding of genotype-phenotype correlations in MODY5 and emphasize the importance of early genetic testing in pediatric patients with antibody-negative diabetes.

Purpose: To describe a previously unreported association between sclerochoroidal calcification and hepatocyte nuclear factor-1β deficiency syndrome. Methods: A single case was reviewed. Results: A 66-year-old man with a history of diabetes mellitus, chronic kidney disease, renal cysts, and prior prostate cancer was found to have bilateral superotemporal placoid sclerochoroidal lesions during routine follow-up. Fundus autofluorescence demonstrated corresponding hyperautofluorescent foci, and optical coherence tomography revealed hyperreflective scleral elevations with posterior shadowing and focal ellipsoid zone disruption. Previous genetic testing identified a pathogenic hepatocyte nuclear factor-1β stop codon variant. The lesions remained stable over 2 years, without evidence of choroidal neovascularization. Conclusions: This case broadens the spectrum of systemic associations with bilateral sclerochoroidal calcification and suggests hepatocyte nuclear factor-1β deficiency syndrome as a potential underlying etiology in patients presenting with bilateral sclerochoroidal calcification and concurrent renal or metabolic abnormalities.