Search Results (69)

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [¹⁸F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [^99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article

Chromophobe renal cell carcinoma (chRCC) is a distinct subtype of non–clear cell renal cell carcinoma (ncRCC), arising from intercalated cells of the distal nephron collecting ducts. No standard treatments are specifically approved for chRCC, which is further hindered by lack of a universally accepted grading system. This study sought to find molecular drivers that may aid in the diagnosis or development of treatments for chRCC. A retrospective analysis of chRCC was conducted using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) repository, accessed through cBioPortal (version 17.0-public) on 21 July 2025. The study examined recurrent somatic mutations and assessed co-occurrence with Benjamini–Hochberg False Discovery Rate (FDR) correction. Additional analyses evaluated mutation by sex and race, with significance set at p < 0.05. The cohort included 180 tumor samples from 170 chRCC patients. Most patients were adults (n = 167, 98.2%) and White (n = 115, 67.6%). Recurrent alterations occurred in genes part of the p53, PI3K/mTOR, Hippo, and NOTCH signaling pathway. Exploratory demographic analyses identified isolated single-patient mutations in select genes across sex and race; however, these rare events are not interpretable as population-level differences. This study provides a comprehensive genomic profile of chRCC across multiple demographic categories. Full article

Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three synchronous primary malignancies involving the liver, left kidney, and right lung. Imaging revealed a hepatic mass with arterial enhancement and portal washout, a large left renal mass, and a cavitated pulmonary nodule. Histopathological and immunohistochemical evaluation confirmed three distinct tumors: well-differentiated hepatocellular carcinoma, chromophobe renal cell carcinoma, and invasive non-mucinous lung adenocarcinoma. A multidisciplinary oncology board recommended surgical resection of the liver and kidney lesions and stereotactic body radiotherapy for the lung tumor. The patient underwent hepatectomy and nephrectomy but experienced severe postoperative complications leading to multi-organ failure and death. Results of the systematic review: A systematic search identified 83 relevant cases of triple primary malignancies after full-text eligibility assessment. None of the 159 articles included after primary screening described a synchronous association of primary liver, kidney, and lung cancers. Conclusions: This case highlights the importance of thorough diagnostic assessment and individualized, multidisciplinary management in patients with multiple synchronous malignancies. To our knowledge, this is the first reported case of synchronous hepatocellular carcinoma, chromophobe renal cell carcinoma, and lung adenocarcinoma. Full article

Background: There is a great deal of knowledge regarding the development of polyomavirus-associated nephropathy and polyomavirus-associated hemorrhagic cystitis in transplant recipients with active BKPyV infection. However, recent studies have revealed a potential association between BKPyV reactivation and certain malignancies, including transitional cell carcinoma, malignant melanoma, colorectal cancer, and prostate cancer. This study aimed to identify a potential link between BKPyV infection and oncogenic transformation in kidney transplant recipients. Methods: Presentation of a case series of kidney transplant recipients diagnosed with polyomavirus-associated nephropathy who developed neoplasms after transplantation. Results: Positive immunohistochemical reactions confirmed the presence of polyomavirus large T antigen in tissue samples from all three patients’ cancers. Furthermore, a case of chromophobe renal cell carcinoma presenting BKPyV proteins in cancer cells was observed for the first time in the literature. Conclusions: BKPyV reactivation was found to be associated with the development of both urothelial cancer, which originates directly from the BKPyV-infected site, and colorectal cancer. Full article

Introduction and Objectives: Local recurrence (LR) in patients treated with surgery for renal cell carcinoma (RCC) remains a significant clinical challenge that requires thorough investigation. Our study aimed to identify the relative risk factors and explore the optimal clinical management of LR. Materials and Methods: We conducted a non-randomized, observational, retrospective multicentric registry involving multiple Italian urological centers. We included patients treated with surgery (either nephron-sparing or radical nephrectomy) who later developed LR, defined as recurrence in the ipsilateral kidney or renal fossa. Patients with hereditary syndromes or metastatic disease at the time of LR diagnosis were excluded. Results: We reported 135 cases of LR with the following characteristics: most primary lesions were monofocal (85.7%), with a median size of 42 mm (23–53), the median R.E.N.A.L. score was 7 (6–8), and the median Padua score was 7 (6–9). Patients were treated with robot-assisted techniques in 59% of cases, laparoscopic surgery in 32.4%, and open surgery in 8.6%. Nephron-sparing surgery was performed in 75.2% of cases. Ischemia occurred in 61% of the cases, with a median ischemia time of 21 min (15.5–24). Intraoperative complications occurred in 3.8% of cases, while postoperative complications were reported in 13.8%, all of which were grade ≤3 according to the Clavien–Dindo classification. The primary tumors were pT1a in 43.5% of cases, pT1b in 26.3%, pT2 in 14.7% and pT3 in 15.5%. Histologically, 84% of cases were clear cell, 11.3% papillary type 1 or 2, and 3.7% chromophobe. Sarcomatoid/rhabdoid variants were present in 10.5% of cases. The median rate of LR was 1.3% (range 0.2–3.6), while the median time to LR was 18 months (12–39). LR occurred in the ipsilateral kidney in 70.5% of cases and in the ipsilateral renal fossa in 29.5%. The median rate of PSM in LR cases at initial surgery was 2.4% (range 0–4.3), while the median rate of negative surgical margin (NSM) in LR cases at initial surgery was 0.1 (0–0.3). Following LR diagnosis, most patients (49.2%) underwent surgery, 29.1% received cryoablation or radiotherapy, 17.1% received systemic treatment alone, and 4.6% followed a watchful waiting/active surveillance approach. At a median follow-up of 62 months, the highest oncological control in terms of 5-year cancer-specific survival and overall survival rates was achieved in surgically treated patients. The PSM, the histological variant, and their combination were found to be independent variables correlated with the occurrence of LR, with relative risks of 3.62, 2.71, and 8.12, respectively. Conclusions: LR after nephron-sparing or radical nephrectomy represents a significant clinical dilemma. Known risk factors are not always sufficient to predict recurrence, emphasizing the necessity of consistent radiological follow-up per guideline recommendations. Early detection of recurrence and a multidisciplinary approach involving expert centers are crucial for optimizing patient outcomes. Full article

Background/Objectives: Despite recent therapeutic advances, the clinical management of renal cell carcinoma (RCC) remains suboptimal. Current treatments are hindered by limited efficacy, the emergence of acquired drug resistance, suboptimal tolerability, and a lack of tumor-specific targeting. While development of novel agents remains an important avenue, it is often constrained by high costs, long development time, and low success rates. As an alternative approach, drug combinations of approved agents offer a promising strategy. Methods: Using our proprietary drug combination methodology, we identified multidrug combinations in RCC cells representing the clear cell (786O) and sarcomatoid chromophobe (UOK276) histological subtypes of RCC. Results: From an initial panel of 10 drugs, either approved or undergoing clinical trial, the optimized drug combinations (ODCs) contained crizotinib, telaglenastat, U-104, and vismodegib at clinical and subtherapeutic doses. The ODCs were non-toxic in advanced hepatic, renal, and cardiac cellular models. Importantly, their anti-tumor activity, already notable in normoxic (21% O₂) conditions (approx. 50%) was markedly enhanced in tumor-relevant hypoxia (1.5% O₂), reaching up to 77% in 2D and 62% in 3D spheroid 786O models. Moreover, chronic exposure of 786O and UOK276 cells led to durable responses, suggesting a prolonged effect in responders. Conclusions: Our findings demonstrate the potential of optimized, non-toxic drug combinations as a highly selective and effective strategy for accelerating the development of precision RCC treatment. Full article

Background/Objectives: Small renal masses (SRMs) are being detected more often due to the increasing use of imaging techniques. Many of these lesions are benign or grow slowly, but a small proportion can exhibit aggressive behavior. Several reports have shown that synchronous metastases may occur even in small renal cell carcinomas (RCCs). Our aim is to assess the malignant potential and the metastatic risk of very small RCCs (≤2 cm). Methods: We reviewed consecutive patients who underwent partial nephrectomy for SRMs at our tertiary referral center between 2005 and 2024, focusing on those with a maximum pathologic diameter ≤ 2 cm. Clinical and pathological data were collected, and cases with aggressive features were described. In addition, a literature search on the Medline/PubMed database was performed to identify previously published cases of RCC ≤ 2 cm and to assess their risk of synchronous metastases (SM). Results: Among 578 patients who underwent partial nephrectomy, 116 patients (20%) had tumors ≤ 2 cm, 90 (77.5%) of which were malignant, whereas 22.5% were benign (oncocytoma = 13%; angiomyolipoma = 5%). Median age and tumor size were 51 yrs and 1.7 cm, respectively. Histology showed clear cell (72.2%), papillary (20%), chromophobe (6.6%), and mixed (0.9%). Two patients (2.2%) experienced aggressive disease: one with synchronous metastases and one with recurrence and later progression. From the literature, we identified 16 additional cases of RCC ≤ 2 cm with synchronous metastases and found an important heterogeneity of results regarding the metastatic potential of SRMs. Conclusions: Although uncommon, synchronous metastases can occur in RCCs even smaller than 1–2 cm. Reported rates for SM of SRMs across the literature range between 1% and 13%, with higher risk observed in tumors larger than 3 cm, but without an absolute safe cutoff. Tumor size alone is therefore insufficient to exclude aggressive potential. Clinical decision-making should consider histology, grade, patient age, radiologic features, and emerging molecular markers to guide surveillance and treatment in this growing patient population. Full article

Introduction: Low-grade oncocytic tumor (LOT) is a recently described renal neoplasm characterized by indolent clinical behavior, a small nested architecture, and distinctive immunophenotypic features. Its distinction from other eosinophilic renal tumors, such as oncocytoma, eosinophilic chromophobe renal cell carcinoma (E-chRCC), and eosinophilic vacuolated tumor (EVT), can be challenging due to overlapping features. The L1 cell adhesion molecule (L1CAM) is being increasingly recognized as a potential diagnostic marker for LOT. Aims: To evaluate the diagnostic performance of L1CAM in distinguishing LOT from morphologically and immunophenotypically similar eosinophilic renal neoplasms. Methods: A total of 54 eosinophilic renal tumors (10 LOTs, 22 oncocytomas, 18 E-chRCCs, and 4 EVTs) were retrospectively collected from five academic institutions and reclassified according to the 2022 WHO criteria. All cases underwent histopathologic review and immunohistochemical analysis for CK7, CD117, GATA3, cathepsin K, and L1CAM. Results: L1CAM showed strong membranous expression in all LOTs (100%) and was negative in oncocytoma, E-chRCC, and EVT, yielding 100% sensitivity and specificity. Traditional markers exhibited overlapping patterns among tumor types. Conclusions: Our findings confirm L1CAM as a highly sensitive and specific marker for LOT, effectively distinguishing it from other eosinophilic renal neoplasms. Incorporating L1CAM into diagnostic panels may enhance accuracy, particularly in challenging cases. Full article

Objectives: The aim of the study was to assess the utility of contrast-enhanced ultrasound (CEUS), using both qualitative and quantitative perfusion analysis, in differentiating subtypes of renal cell carcinoma (RCC). Methods: This prospective, single-center study includes 91 patients with histologically confirmed RCC. We performed a CEUS within one week prior to nephrectomy. Qualitative parameters (enhancement pattern, heterogeneity, pseudocapsule) and quantitative perfusion metrics were assessed. Logistic regression models were developed to evaluate the diagnostic performance of CEUS in differentiating high-grade (clear cell RCC) from low-grade RCC (papillary and chromophobe). Results: Qualitative CEUS findings showed that hyperenhancement and isoenhancement were significantly associated with high-grade RCC (OR = 38.3 and OR = 7.8, respectively; p < 0.001 and p = 0.014). Hypoenhancement was predominant in low-grade RCC (80.0%). Quantitative parameters, including peak enhancement and wash-in/wash-out area under the curve, significantly differed between tumor grades (p < 0.001). A model using qualitative parameters alone achieved an AUC of 0.847 and 81.9% accuracy. Adding quantitative metrics marginally improved performance (AUC 0.912, accuracy 86.2%), though not significantly. Conclusions: CEUS provides valuable diagnostic information in differentiating RCC subtypes, with qualitative parameters alone demonstrating strong predictive power. While quantitative analysis slightly enhances diagnostic accuracy, its added value may be limited by technical challenges. Full article

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogenous group of malignancies with varying degrees of clinical aggressiveness and response to different systemic therapies. As the characterization of subtypes of nccRCC continues to evolve, it is important to understand the evidence around systemic treatments used in advanced or metastatic stages of specific subtypes. Here, we review the literature on systemic therapies in nccRCC, with a focus on prospective trials that included patients with papillary renal cell carcinoma (RCC), chromophobe RCC, RCC not further classified/unclassified RCC, translocation RCC, collecting duct RCC, and renal medullary carcinoma. We also review emerging treatments for other molecularly defined subtypes of this disease. Full article

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This research investigates the genotype and expression levels of FTO and ALKBH5 in RCC patients from the Middle East and Northern Africa (MENA) region. Methods: Formalin-fixed paraffin-embedded samples from the kidney biopsies of RCC patients and controls were examined using targeted DNA sequencing, whole transcriptome profiling, and immunohistochemistry. Results: Our findings show that the rs11075995T variant in FTO is associated with a heightened risk of clear-cell RCC (ccRCC). ALKBH5 and FTO protein expression were significantly lower in ccRCC and chromophobe RCC (chRCC) patients but not in papillary RCC (pRCC) patients. In ccRCC, transcriptomic data revealed a significant downregulation of FTO (log₂FC = −5.2, q < 0.001) and ALKBH5 (log₂FC = −4.7, q < 0.001) compared to controls. A significant negative correlation was found in ccRCC between FTO expression and T allele frequency in rs11075995, suggesting that FTO expression is affected. Conclusions: This is the first demonstration of the association of the dysregulated expression of FTO and ALKBH5 in ccRCC and chRCC patients from the MENA region. FTO variant rs11075995T increased the risk of ccRCC and was negatively associated with FTO protein expression. Full article

Kidney and renal pelvic cancer are a significant cause of cancer-related deaths, with the most common malignant kidney tumor being renal cell carcinoma (RCC). Chromophobe renal cell carcinoma is a rarer form of RCC that poses significant challenges to accurate diagnosis, as it shares many histologic features with Oncocytoma, a benign renal tumor. Biopsies for histopathological and immunohistochemical analysis have limitations in distinguishing chromophobe RCC from Oncocytoma. Syndromic cases may also have tumors with overlapping features. Techniques such as infrared (IR) spectroscopic imaging have shown promise as an alternative approach to tissue diagnostics. In this study, we propose a deep-learning-based framework for automating classification in kidney tumor tissue microarrays (TMAs) using an IR dataset. Feature selection algorithms reduce data dimensionality, followed by a deep learning classification approach. A classification accuracy of 91.3% was observed for validation data, even with the use of 13.6% of all wavelengths, thereby reducing training time by 21% compared to using the entire spectrum. Through the integration of scalable deep learning models coupled with feature selection, we have developed a classification pipeline with high predictive power, which could be integrated into a high-throughput real-time IR imaging system. This would create an advanced diagnostic tool for the detection and classification of renal tumors, namely chromophobe RCC and Oncocytoma. This may impact patient outcomes and treatment strategies. Full article

Renal cell carcinoma (RCC) is a heterogeneous disease that represents the most common type of kidney cancer. The classification of RCC is primarily based on distinct morphological and molecular characteristics, with two broad categories: clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC). Clear cell RCC is the predominant subtype, representing about 70–80% of all RCC cases, while non-clear cell subtypes collectively make up the remaining 20–30%. Non-clear cell RCC encompasses many histopathological variants, each with unique biological and clinical characteristics. Additionally, any RCC subtype can undergo sarcomatoid dedifferentiation, which is associated with poor prognosis and rapid disease progression. Recent advances in molecular profiling have also led to the identification of molecularly defined variants, further highlighting the complexity of this disease. While immunotherapy has shown efficacy in some RCC variants and subpopulations, significant gaps remain in the treatment of rare subtypes. This review explores the outcomes of immunotherapy across RCC subtypes, including rare variants, and highlights opportunities for improving care through novel therapies, biomarker-driven approaches, and inclusive clinical trial designs. Full article

Background/Objectives: Renal cell carcinoma is an aggressive form of kidney cancer, contributing to an estimated 138,000 deaths globally in 2017. Traditional treatments like chemotherapy and radiation are generally considered ineffective. Additionally, CD47 has been identified as a crucial tumor antigen involved in the development and progression of various cancers, including renal cell carcinoma. The interaction of CD47 with SIRPα triggers a “don’t eat me” signal to the macrophages, inhibiting phagocytosis. Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (STs) and hematological malignancies. This study aimed to evaluate CD47 expression in malignant and benign renal cell tumors and compare it with prognostic histopathological parameters. Methods: We included 160 malignant and 26 benign tumors. The malignant tumors consisted of renal cell carcinoma (RCC) subtypes including 37 clear cell, 30 chromophobe, 30 papillary type 1, 29 papillary type 2, and 34 unclassified RCC cases. As for the benign tumors, we included 26 oncocytoma cases. All samples were stained with anti-CD47 antibodies by immunohistochemistry methods. Results: The statistical analysis yielded a significant correlation between CD47 expression and survival, metastasis, and capsule invasion for the unclassified RCC cases. We did not find any further significant correlation between CD47 expression and the studied parameters. Conclusions: To the best of our knowledge, our study is the first to research CD47 expression in benign and malignant renal carcinoma subtypes. Further large-scale studies are needed to determine the expression profile of CD47 in renal cell tumors. Full article

RO and ChRCC are kidney tumours with overlapping characteristics, making differentiation between them challenging. The objective of this research is to create a radiogenomics map by correlating radiomic features to molecular phenotypes in ChRCC and RO, using resection as the gold standard. Fourteen patients (6 RO and 8 ChRCC) were included in the prospective study. A total of 1,875 radiomic features were extracted from CT scans, alongside 632 cytobands containing 16,303 genes from the genomic data. Feature selection algorithms applied to the radiomic features resulted in 13 key features. From the genomic data, 24 cytobands highly correlated with histology were selected and cross-correlated with the radiomic features. The analysis identified four radiomic features that were strongly associated with seven genomic features. These findings demonstrate the potential of integrating radiomic and genomic data to enhance the differential diagnosis of RO and ChRCC, paving the way for more precise and non-invasive diagnostic tools in clinical practice. Full article