Search Results (81)

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. 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

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Currently, there is no standard treatment for renal cell carcinoma (RCC) that is free of side effects and resistance. Additionally, limited information exists on how curcumin affects the gene expression profiles of patients with translocation renal cell carcinoma (tRCC) and papillary renal cell carcinoma (pRCC). The pathways responsible for metastasis in tRCC are still not well understood, and there is no established treatment or reliable biomarker to predict outcomes for metastatic tRCC. Primary clinical data from patients were retrieved from the TCGA database and analyzed using cBioPortal, stitch, string, R and Python. Various analyses were performed, including differential gene expression, protein-protein interaction (PPI) network analysis, drug-targeted gene analysis, gene ontology (GO), enrichment analyses, and systematic searches to assess the impact of curcumin on the transcriptomic profiles of tRCC, pRCC, and clear cell renal cell carcinoma (ccRCC). No significant impact of sensitive genes on survival in KIRC and KIRP was found, though a trend suggested they may delay disease progression. The combination of curcumin with sunitinib showed promise in overcoming drug resistance in ccRCC by inducing ferroptosis, reducing iron, and increasing ADAMTS18 expression. This study, leveraging data from the TCGA database and other databases explored the impact of curcumin on transcriptomic profiles in tRCC, pRCC, and clear cell RCC (ccRCC). Gene analysis revealed immune and metabolic differences, with KIRC showing a stronger immune response. This study is the first to propose that future research into the miR-148/ADAMTS18 genes and the ferroptosis pathway in tRCC and pRCC could lead to the development of new therapies and the identification of novel therapeutic targets, potentially overcoming drug resistance and metastasis. Full article

Background: Differentiating histologic subtypes of fat-poor small renal masses using conventional imaging remains difficult due to their overlapping radiologic characteristics. We aimed to develop a machine learning-based diagnostic model using CT-derived radiomic features to classify the five most common renal tumor subtypes: clear cell RCC (ccRCC), papillary RCC (pRCC), chromophobe RCC (chRCC), angiomyolipoma (AML), and oncocytoma. Methods: A total of 499 patients with pathologically confirmed renal tumors who underwent preoperative contrast-enhanced CT and nephrectomy were retrospectively analyzed. Results: We extracted and analyzed radiomic features from 1548 multi-phase CT scans from 499 patients, focusing on fat-poor tumors. Five machine learning classifiers including Linear SVM, Rbf SVM, Random Forest, and XGBoost were involved. Among the models, XGBoost showed the best classification performance, with an average AU-PRC: mean = 0.757, standard error = 0.033 and a renal angiomyolipoma-specific AU-ROC: mean = 0.824, standard error = 0.023. These results outperformed other single-phase CT radiomic feature-based machine learning models trained with 20% of principal components. Conclusions: This study demonstrates the effectiveness of radiomics-based machine learning in classifying renal tumor subtypes and highlights the potential of AI in medical imaging. The findings, particularly the utility of single-phase CT and feature optimization, offer valuable insights for future precision medicine approaches. Such methods may support more personalized diagnosis and treatment planning in renal oncology. 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

Background and Objective. The significance of microRNAs (miRNAs) in relation to neoplastic diseases; such as renal carcinoma carcinoma (RCC); has been brought to light by recent studies. Analyzing the main urinary miRNAs implicated in RCC and their potential diagnostic use was the goal of this systematic review of the literature. Methods. This systematic review was performed following the PROSPERO protocol CRD42024550716. Our literature search strategies were deciding which database to include (Pubmed; EMBASE and Clinicaltrial.gov) and composing strings with words related to urinary miRNA in patients with RCC. Key findings and limitations. After screening; 10 papers were included from the 593 records that the systematic review found. No miRNA was investigated in more than one paper by different authors. The miR-210 and let-7 family were the most investigated and resulted upregulated in RCC cases compared to controls. Five papers reported different expression of miRNAs in urine samples before and after surgery: miR-15a; miR-34a-5p; miR-200a-3p; miR-205-5p; miR-210; miR-210-3p; miR-365a-3p and let-7d-5p levels decreased after nephrectomy. Meta-analysis was not performed since the included studies were heterogeneous; in terms of studied miRNA; of the normalizer used during stabilization phase; and histologic type of RCC (clear cell RCC; papillary RCC; unspecified RCC). Conclusions. Considering the variability and heterogeneity of the obtained results; as well as the vastness of the topic; expanding research in this field appears highly promising. To support further advancements; it would be useful to establish a database that consolidates international findings. Full article

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney tumor which is usually characterized by indolent disease physiology. While several high-grade and sarcomatoid MTSCC tumors have been reported, the clinical experience with contemporary immune checkpoint blockade (ICB) combination therapies extrapolated from treatment paradigms of conventional renal cell carcinoma (RCC) remains limited. Here, we report two patients with metastatic MTSCC treated with first-line ipilimumab plus nivolumab therapy who both achieved great clinical benefit. We subsequently performed immune deconvolution analysis on previously identified MTSCC-like kidney tumors from The Cancer Genome Atlas (TCGA) and discovered significantly higher PD-L1 transcriptomic expression compared to similar papillary RCC tumors, providing additional biomarker data supporting the observed ICB response. These data implicate ICB therapy as an effective treatment for patients with metastatic MTSCC. 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

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann–Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression. Full article

Objectives: To determine the rate of benign pathology in cT1 tumors following partial nephrectomy in the Netherlands, thereby evaluating the rate of overtreatment. Methods: Data were collected from a nationwide database containing histopathology of resected renal tissue from 2014 to 2022. Patients who underwent partial nephrectomy for suspected RCC staged T1a-b were extracted for analysis. Data are shown in percentages, and multivariable logistic regression was performed to determine predictive factors for benign pathology. Results: 3409 cases were analyzed, of which 403 (12%) were benign and 3006 (88%) malignant. Subtype analysis showed 2126 (62%) cases of clear-cell RCC, followed by 604 (18%) of papillary RCC and 344 (10%) oncocytomas. Mean age was 63 years among patients with malignant pathology versus 65 years for patients with benign lesions (p < 0.001). Mean tumor size was 3.2 cm for malignant pathology and 2.9 cm for benign (p < 0.001). The rates of benign and malignant pathology did not change between 2014 and 2022 (p = 0.377). Multivariable regression showed age ≥ 65 years (65–79 years [OR 1.881, p = 0.002], ≥ 80 years [OR 3.642, p < 0.001]) and tumor size (OR 0.793, p < 0.001) as predictors for benign pathology. The main limitation of this study is that we do not know the biopsy rate of our cohort. Conclusion: This study reports a low rate of 12% benign pathology after partial nephrectomy in the Netherlands. It remains debatable whether these rates are acceptable, or if renal tumor biopsies should be utilized more frequently to reduce overtreatment. Full article

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available. Full article

Renal cell carcinoma (RCC) is a significant oncological challenge due to its heterogeneous nature and limited treatment options. The PAX developmental gene family encodes nine highly conserved transcription factors that play crucial roles in embryonic development and organogenesis, which have been implicated in the occurrence and development of RCC. This review explores the molecular landscape of RCC, with a specific focus on the role of the PAX gene family in RCC tumorigenesis and disease progression. Of the various RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most prevalent, characterized by the loss of the von Hippel–Lindau (VHL) tumor suppressor gene. Here, we review the published literature on the expression patterns and functional implications of PAX genes, particularly PAX2 and PAX8, in the three most common RCC subtypes, including ccRCC, papillary RCC (PRCC), and chromophobe RCC (ChRCC). Further, we review the interactions and potential biological mechanisms involving PAX genes and VHL loss in driving the pathogenesis of RCC, including the key signaling pathways mediated by VHL in ccRCC and associated mechanisms implicating PAX. Lastly, concurrent with our update regarding PAX gene research in RCC, we review and comment on the targeting of PAX towards the development of novel RCC therapies. Full article