Features Of Renal Cell Carcinoma Research Articles

Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features.

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.

The Prevalence and Radiologic Features of Renal Cancers Associated with FLCN, BAP1, SDH, and MET Germline Mutations.

Purpose To investigate the prevalence of FLCN, BAP1, SDH, and MET mutations in an oncologic cohort and determine the prevalence, clinical features, and imaging features of renal cell carcinoma (RCC) associated with these mutations. Secondarily, to determine the prevalence of encountered benign renal lesions. Materials and Methods From 25 220 patients with cancer who prospectively underwent germline analysis with a panel of more than 70 cancer-predisposing genes from 2015 to 2021, patients with FLCN, BAP1, SDH, or MET mutations were retrospectively identified. Clinical records were reviewed for patient age, sex, race/ethnicity, and renal cancer diagnosis. If RCC was present, baseline CT and MRI examinations were independently assessed by two radiologists. Summary statistics were used to summarize continuous and categorical variables by mutation. Results A total of 79 of 25 220 (0.31%) patients had a germline mutation: FLCN, 17 of 25 220 (0.07%); BAP1, 22 of 25 220 (0.09%); SDH, 39 of 25 220 (0.15%); and MET, one of 25 220 (0.004%). Of these 79 patients, 18 (23%) were diagnosed with RCC (FLCN, four of 17 [24%]; BAP1, four of 22 [18%]; SDH, nine of 39 [23%]; MET, one of one [100%]). Most hereditary RCCs demonstrated ill-defined margins, central nonenhancing area (cystic or necrotic), heterogeneous enhancement, and various other CT and MR radiologic features, overlapping with the radiologic appearance of nonhereditary RCCs. The prevalence of other benign solid renal lesions (other than complex cysts) in patients was up to 11%. Conclusion FLCN, BAP1, SDH, and MET mutations were present in less than 1% of this oncologic cohort. Within the study sample size limits, imaging findings for hereditary RCC overlapped with those of nonhereditary RCC, and the prevalence of other associated benign solid renal lesions (other than complex cysts) was up to 11%. Keywords: Familial Renal Cell Carcinoma, Birt-Hogg-Dubé Syndrome, Carcinoma, Renal Cell, Paragangliomas, Urinary, Kidney © RSNA, 2024.

Clinicopathological and molecular features of renal cell carcinomas with haemangioblastoma-like features distinct from clear cell renal cell carcinoma.

Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra-neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma-like features have exhibited both clear cell renal cell carcinoma (CCRCC)- and haemangioblastoma-like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma-like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma. Four RCCs with haemangioblastoma-like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma-like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma-like features had a well-circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma-like features exhibited CCRCC-like areas with indistinct tubular structures and foci of haemangioblastoma-like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma-like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma-like features exhibited a unique immunohistochemical profile, with positive staining for inhibin-α, S100, carbonic-anhydrase-9, keratin7, and high molecular weight keratin and negative staining for (alpha-methylacyl-CoA racemase) AMACR. RCC with haemangioblastoma-like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G). The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma-like features is a distinct entity from CCRCC.

DNA Methylation Modification Patterns Identify Distinct Prognosis and Responses to Immunotherapy and Targeted Therapy in Renal Cell Carcinoma.

Considering the remarkable heterogeneity of biological features of renal cell carcinoma (RCC), the current clinical classification that only relies on classic clinicopathological features is in urgent need of improvement. Herein, we aimed to conduct DNA methylation modification patterns in RCC. We retrospectively curated multiple RCC cohorts, comprising TCGA-KIRC, TCGA-KICH, TCGA-KIRP, and E-MTAB-1980. DNA methylation modification patterns were proposed with an unsupervised clustering algorithm based on 20 DNA methylation regulators. Immunological features were characterized using tumor-infiltrating immune cells and immunomodulators. Sensitivity to immuno- or targeted therapy was estimated with submap and Genomics of Drug Sensitivity in Cancer (GDSC). DNA methylation score (DMS) was developed with principal component analysis. Three DNA methylation modification patterns were conducted across RCC patients, namely C1, C2 and C3. Among them, C3 displayed the most remarkable survival advantage. The three patterns presented in agreement with immune phenotypes: immune-desert, immune-excluded, and immune-inflamed, respectively. These patterns displayed distinct responses to anti-PD-1 and targeted drugs. DMS enabled the quantification of DNA methylation status individually as an alternative tool for prognostic estimation. The DNA methylation molecular patterns we proposed are an innovative complement to the traditional classification of RCC, which might contribute to precision medicine.

Computer tomography-based shape of tumor contour and texture of tumor heterogeneity are independent prognostic indicators for clinical T1b-T2 renal cell carcinoma.

To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes. Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death. A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively.

Genomic profiles of renal cell carcinoma in a small Chinese cohort.

Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

An automated surgical decision-making framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features in renal cell carcinoma

ObjectivesTo determine whether 3D-CT multi-level anatomical features can provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma.MethodsThis is a retrospective study based on multi-center cohorts. A total of 473 participants with pathologically proved renal cell carcinoma were split into the internal training and the external testing set. The training set contains 412 cases from five open-source cohorts and two local hospitals. The external testing set includes 61 participants from another local hospital. The proposed automatic analytic framework contains the following modules: a 3D kidney and tumor segmentation model constructed by 3D-UNet, a multi-level feature extractor based on the region of interest, and a partial or radical nephrectomy prediction classifier by XGBoost. The fivefold cross-validation strategy was used to get a robust model. A quantitative model interpretation method called the Shapley Additive Explanations was conducted to explore the contribution of each feature.ResultsIn the prediction of partial versus radical nephrectomy, the combination of multi-level features achieved better performance than any single-level feature. For the internal validation, the AUROC was 0.93 ± 0.1, 0.94 ± 0.1, 0.93 ± 0.1, 0.93 ± 0.1, and 0.93 ± 0.1, respectively, as determined by the fivefold cross-validation. The AUROC from the optimal model was 0.82 ± 0.1 in the external testing set. The tumor shape Maximum 3D Diameter plays the most vital role in the model decision.ConclusionsThe automated surgical decision framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features exhibits robust performance in renal cell carcinoma. The framework points the way towards guiding surgery through medical images and machine learning.Clinical relevance statementWe proposed an automated analytic framework that can assist surgeons in partial or radical nephrectomy decision-making. The framework points the way towards guiding surgery through medical images and machine learning.Key Points• The 3D-CT multi-level anatomical features provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma.• The data from multicenter study and a strict fivefold cross-validation strategy, both internal validation set and external testing set, can be easily transferred to different tasks of new datasets.• The quantitative decomposition of the prediction model was conducted to explore the contribution of each extracted feature.

Based on disulfidptosis, revealing the prognostic and immunological characteristics of renal cell carcinoma with tumor thrombus of vena cava and identifying potential therapeutic target AJAP1.

Patients with clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus have a poor prognosis, high surgical risk, and lack of targeted therapeutic agents. Genes with consistent differential expression trends in tumor tissues and VTT groups were first screened, and then differential genes associated with disulfidptosis were found by correlation analysis. Subsequently, identifying ccRCC subtypes and constructing risk models to compare the differences in prognosis and the tumor microenvironment in different subgroups. Finally, constructing a nomogram to predict the prognosis of ccRCC and validate key gene expression levels in cells and tissues. We screened 35 differential genes related to disulfidptosis and identified 4 ccRCC subtypes. Risk models were constructed based on the 13 genes, and the high-risk group had a higher abundance of immune cell infiltration, tumor mutational load, and microsatellite instability scores, predicting high sensitivity to immunotherapy. The 1-year AUC = 0.869 for predicting OS by nomogram has a high application value. The expression level of the key gene AJAP1 was low in both tumor cell lines and cancer tissues. Our study not only constructed an accurate prognostic nomogram for ccRCC patients but also identified an AJAP1 biomarker as a potential biomarker for the disease.

Abstract 1416: Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis

Abstract Introduction: Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study’s goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Materials and Methods: Frozen kidney samples were obtained from 48 patients who were undergoing dialysis treatment and developed RCC at Iwate Medical University Hospital. Among them, we selected 38 subjects for study from whom matched tumor and adjacent non-tumor tissue samples could be obtained and from which DNA (n=38) or RNA (n=26) could be isolated. We performed whole genome sequencing of genomic DNA using MGIEasy FS DNA Library Prep Set and short read sequencer DNBSEQ-G400. mRNA Sample were sequenced using HiSeq. Driver events, copy-number alteration (CNA) analysis, and mutational signature profiling was performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels, and structural variants as well as CNAs, while transcriptome data was analyzed for differentially expressed genes and through gene set enrichment analysis. Results: ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All ACD (acquired cystic disease)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation, and targets of Myc. Conclusion: This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis. Citation Format: Shigekatsu Maekawa, Masahi Fujita, Ryo Takata, Daiki Ikarashi, Tomohiko Matsuura, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Jun Sugimura, Takaya Abe, Hidewaki Nakagawa, Wataru Obara. Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1416.

The clinical significance of computed tomography texture features of renal cell carcinoma in predicting pathological T1-3 staging.

Precise T staging is an important prerequisite for the treatment decisions of patients with renal cell carcinoma (RCC). We aimed to predict the pathological T1-3 staging of RCC with an automatic multiclass T staging prediction mode. We retrospectively enrolled 100 consecutive patients with pathologically proven RCC that was newly diagnosed and untreated from Sun Yat-sen University Cancer Center and randomly split these patients into a training set (70%) and an internal testing set (30%). We enrolled additional 29 patients with pathologically proven RCC from The Third Affiliated Hospital of Shenzhen University as the external testing set. We used the training set data to establish a prediction model for pathological T1-3 staging of RCC and validated the effect of the training model using the internal and external testing sets. Quantitative decomposition of the prediction model was conducted to explore the contribution of each extracted feature. The computed tomography (CT) images of 100 patients (37, 29, and 34 patients with T1, T2, and T3 staging, respectively, according to the eighth tumor-node-metastasis staging system) were used to establish the prediction model for T staging using delineation of the target area, image segmentation, and feature extraction. The micro area under the curve (AUC) and macro-AUC of the model were 0.90 [95% confidence interval (CI): 0.84-1.00] and 0.91 (95% CI: 0.86-1.00), respectively. In terms of validation with the external testing set, the micro-AUC and macro-AUC were 0.72 (95% CI: 0.66-0.84) and 0.78 (95% CI: 0.69-0.88), respectively. Our prediction model showed good performance in predicting the pathological T1-3 staging of RCC.

The role of three-dimensional models in preoperative communication and postoperative management of partial nephrectomy

ObjectiveThis study aims to examine the significance of utilizing three-dimensional (3D) image reconstruction technique in preoperative communication prior to partial nephrectomy (PN) and its impact on postoperative follow-up. MethodsA retrospective study was performed with 158 renal cancer patients treated with PN at our center from May 1, 2017 to April 30, 2019. 81 patients (group A) had preoperative communication using the 3D reconstruction technique, while 77 patients (group B) did not. The surgeon explained the anatomical structure, tumor characteristics, and surgical approach in detail to the two groups of patients. Each patient completed a questionnaire. The loss to follow-up rate over a 3-year period was counted for both groups, and non-cancer-related serious complications such as renal failure and cardio-cerebrovascular disease were observed. This research did not include patients who returned for follow-up care owing to associated complications such as postoperative chronic kidney disease. Comparisons between two groups were performed using the Mann–Whitney U test and chi-square test. ResultsAll patients showed no statistically significant differences in basic clinical parameters, such as age, gender, body mass index, tumor size, and R.E.N.A.L. score (P ​> ​0.05). In group A, patients were significantly more likely to experience understanding of renal anatomy (P ​= ​0.001), characteristics of renal cell carcinoma (P ​= ​0.003), surgical approach (P ​= ​0.007), and relief of preoperative anxiety (P ​= ​0.013). The follow-up adherence at 3 years postoperatively in group A and group B was 21 cases and 10 cases, respectively (P ​= ​0.041). In addition, glomerular filtration rate < 60 ​mL/min/1.73 ​m2 or serum creatinine > 186 ​μmol/L at 3 years after surgery occurred in 5 patients in group A and 13 in group B (P ​= ​0.034), and a systolic blood pressure rise greater than 20 ​mmHg occurred in 9 patients in group A and 18 in group B (P ​= ​0.041). ConclusionsThe findings of this study suggest that the integration of 3D reconstruction techniques in preoperative communication effectively enhances patients’ understanding and perception of kidney tumors and PN. Moreover, the utilization of these techniques can contribute to the prevention of significant non-cancer-related complications during the postoperative phase.

Omics sciences and precision medicine in kidney cancer.

In the last decade, renal carcinoma has become more prevalent in European and North American regions. Kidney tumors are usually categorized based on histological features, with renal cell carcinoma being the most common subtype in adults. Despite conventional diagnostic and therapeutic strategies, a rise in cancer incidence and recurrence necessitates a fresh approach to diagnosing and treating kidney cancer. This review focuses on novel multi-omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, and microbiomics, to better understand the molecular and clinical features of renal cell carcinoma. Studies integrating omics sciences have shown early promise in enhancing prognostic and therapeutic outcomes for various kidney cancer subtypes and providing insight into fundamental pathophysiological mechanisms occurring at different molecular levels. This review highlights the importance of utilizing omics sciences as a revolutionary concept in diagnostics and therapeutics and the clinical implications of renal cell carcinoma. Finally, the review presents the most recent findings from large-scale multi-omics studies on renal cell carcinoma and its associations with patient subtyping and drug development.

Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis

Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis

Exploring Renal Malignancies in Saudi Arabia: Insights from a Tertiary Care Center Study.

This retrospective study aims to describe the characteristics of renal cell carcinoma (RCC) in Saudi Arabia, in terms of epidemiology, clinical presentation, tumor subtype, Fuhrman grade, tumor size and stage, and overall survival. A total of 431 adult patients with a histopathological diagnosis of RCC between 2015 and 2023 were included in the analysis. Most patients (72.4%) had clear cell tumors, followed by chromophobe (15.1%) and papillary (12.5%) subtypes. In males, papillary RCC (85.2%) was more common compared to clear cell (59.8%) and chromophobe (67.7%) subtypes. Significant differences were observed in median body mass index (BMI) across tumor subtypes, and papillary tumor patients exhibited the highest incidence of hematuria (33.3%) compared to other subtypes. The Fuhrman grade also varied significantly among RCC types. Survival times were found to be lower for patients with papillary tumors. No significant difference was observed based on patients' nationality. This study can inform clinical decision-making on patient prognosis and management as well as public health efforts aimed at reducing the alarming rise of RCC incidence.

Analysis of the EPAS-1 Expression Level and Pathological Characteristics of Renal Cell Carcinoma

Analysis of the EPAS-1 Expression Level and Pathological Characteristics of Renal Cell Carcinoma

Renal carcinoma with metastatic spread in a tiger (Panthera tigris): morphological and immunohistochemical study.

A 12‑year‑old intact male Panthera tigris presented with pain and weight loss was euthanatized. Necroscopical examination revealed a neoplastic mass expanding to the left renal pelvis with metastatic dissemination to local lymph node, adrenal gland, and lung. Immunohistochemical characterization was performed revealing co‑expression of both cytokeratin and vimentin and negativity for both PAX8 and c‑KIT. Considering histochemical and immunohistochemical results the tumour was classified as renal cell carcinoma with metastatic spread. This report provides insights into the morphological and immunohistochemical features of renal cell carcinoma in Panthera tigris.

Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer.

Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8+ Tcell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target.

Clinicopathologic features of renal cell carcinomas seen at the Aga Khan University Hospital in Kenya.

Kidney cancer accounted for 1. 8% of global cancer deaths according to Globocan 2020 estimates, with most of these being renal cell carcinomas. Lower rates of renal cell carcinoma are reported for Africa and these are expected to change for a combination of reasons. The clinical and morphologic characteristics of renal cell carcinoma seen within Kenya have not been described before. This study aims to partially fill this gap. This was a cross-sectional descriptive study examining electronic histopathology reports from the Aga Khan University Hospital Nairobi Laboratory for the period January 2016 to May 2022. Sixty cases of renal cell carcinoma were identified. The mean age at diagnosis was 55.3 years. The most common histologic subtype diagnosed was clear cell renal cell carcinoma (41.7%), followed by papillary renal cell carcinoma and renal cell carcinoma not further specified (both 21.7%), and chromophobe renal cell carcinoma (11.7%). The most frequent specimen type was resection, followed by cores of renal masses. The mean tumor size was 8.5 cm. Sixty-seven percent of patients presented with Stage III and above. Renal masses were the commonest clinical indication for biopsy among the records reviewed. The male to female ratio, as well as the mean age at presentation were comparable to what is described in literature for other regions of the world. The proportions of the commonest histologic subtypes matched what is described in other parts of the world. Challenges in the identification of histologic subtypes included having a limited panel of antibodies for diagnosis and the lack of genetic molecular tests for histotyping. The spectrum of histologic subtypes of renal cell carcinoma seen at a tertiary referral hospital in Nairobi, Kenya was similar to that described in other parts of Africa and the globe. The age at presentation with renal cell carcinoma was consistent with what has been described in literature. Challenges were identified in the accurate histotyping of renal cell carcinoma due to constrained resources. Majority of cases diagnosed presented at advanced stage.

Association between decreased ipsilateral renal function and aggressive behavior in renal cell carcinoma

BackgroundTo assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients. MethodsWe examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included.ResultsAmong 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25, p < 0.001), high Fuhrman grade (grade 3–4) (41.7% vs. 55.6%, p < 0.001), and high T stage (T stage 3–4) (9.0% vs. 20.1%, p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5–7) (hazard ratio [HR] 11.9, p < 0.001) and SSIGN (8–10) (HR 69.2, p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75, p = 0.065) showed borderline significance. Kaplan–Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached, p < 0.001).ConclusionsAmong unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.

Blood Perfusion Characteristics of Renal Cell Carcinoma in the Process of Tumor Growth: Monitored With Multiple Sonographic Modalities.

Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter ( d ), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mm < d ≤ 10 mm, and d > 10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d > 10 mm than those d < 10 mm ( P < 0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P < 0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI ( P < 0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those >10 mm ( P < 0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.