Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

Label-Free SERS of Urine Components: A Powerful Tool for Discriminating Renal Cell Carcinoma through Multivariate Analysis and Machine Learning Techniques.

The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection.

Wide-Targeted Semi-Quantitative Analysis of Acidic Glycosphingolipids in Cell Lines and Urine to Develop Potential Screening Biomarkers for Renal Cell Carcinoma.

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC-MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.

Histomorphometric and Immunohistochemical Diagnosis of Renal Cell Carcinoma: Review Article.

Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and is among the 10 most common cancers worldwide. Incidence of renal cell carcinoma is 400,000 individuals worldwide per year. The age of diagnosis is approximately 60years, and twice as many men are diagnosed as women. African Americans have a slightly higher rate of RCC than do White peoples. The reasons for this are not clear. Inherited syndromes in family, long term dialysis, smoking individuals who had quit smoking >10 years prior had a lower risk when compared to those who had quit <10 years. 22.5 pack-year smokers had a more than 50.0% increased RCC risk compared to nonsmokers, high body mass index i.e. 5kg/m2 increase in body mass index (BMI) was found to be strongly associated with RCC. BMI >35kg/m2 is associated with higher incidence of Cancer raise blood pressure- Higher BMI and hypertension were independently shown to increase the long-term risk of RCC in men. A rise of blood pressure of 10mmHg is associated with 10-22 percent risk of RCC. Clear cell carcinoma is the most common variety of renal cell carcinoma as compared to other varieties of renal cell carcinomas (68.0-75.0%). It has also been found that CAIX is positive for all papillary renal cell carcinoma and negative for CK7, AMACR & TEF. We also found that CK7, EMA, CD117 and CAIX are most commonly positive for all chromophobe renal cell carcinoma. It has been found that clear cell carcinoma is the most common variety of renal cell carcinoma as compared to other varieties of renal cell carcinomas (68.0-75.0%). Again it has also been found that CAIX is positive for all papillary renal cell carcinoma and negative for CK7, AMACR and TEF. Here it has been found that chromophobe carcinoma is most commonly positive for CK7, EMA, CD117 and CAIX. In a patient coming with signs and symptoms of renal cell carcinoma can be confirmed with the help of histoimmunological markers and in that case one can plan for a proper planning of management.

Heterotopic bone formation in a case of clear cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.

Isolated intracholecystic metastasis of renal cell carcinoma: A report of a rare case.

Renal cell carcinomas are known for their unforeseeable metastatic pattern. They are known to have high metastatic potential, thus commonly associated with synchronous or metachronous metastatic presentation. At the time of diagnosis, approximately one-third of patients present with metastatic disease. We present a case of synchronous metastasis of clear cell carcinoma to the gallbladder in a 54-year-old male within two months after radical nephrectomy.

Endolymphatic sac tumor misdiagnosed as metastatic renal cell carcinoma: Pitfalls in morphology and immunohistochemistry.

Endolymphatic sac tumor (ELST) is a rare disease that originates from the endolymphatic sac system of the inner ear. Being a low-grade malignant tumor, ELST has a mild morphology and is characterized by a slow but aggressive growth. Most clinicians and pathologists are unfamiliar with this disease. ELST can be misdiagnosed as metastatic renal cancer because of the similarity in morphology and expression of nephrogenic markers such as PAX8. The presented case of a 27-year-old man revealed that observing the characteristic location and confirming the absence of renal neoplasm to rule out the possibility of metastasis are critical for obtaining an accurate final diagnosis.

Humoral complementomics - exploration of noninvasive complement biomarkers as predictors of renal cancer progression.

Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a Humoral Complementomics approach: a work-up of assays to comprehensively evaluate complement proteins, activation fragments, and autoantibodies targeting complement proteins in plasma, which we correlated with the intratumoral complement activation, and/or local production, focusing on localized and metastatic clear cell renal cell carcinoma (ccRCC). In two prospective ccRCC cohorts, plasma C2, C5, Factor D and properdin were elevated compared to healthy controls, reflecting an inflammatory phenotype that correlated with plasma calprotectin levels but did not associate with CRP or with patient prognosis. Conversely, autoantibodies against the complement C3 and the reduced form of FH (a tumor neo-epitope reported in lung cancer) correlated with a favorable outcome. Our findings pointed to a specific group of patients with elevated plasma C4d and C1s-C1INH complexes, indicating the initiation of the classical pathway, along with elevated Ba and Bb, indicating alternative pathway activation. Boostrapped Lasso regularized Cox regression revealed that the most predictive complement biomarkers were elevated plasma C4d and Bb levels at the time of surgery, which correlated with poor prognosis. In conclusion, we propose Humoral Complementomics as an unbiased approach to study the global state of the complement system in any pathological plasma sample and disease context. Its implementation for ccRCC revealed that elevated C4d and Bb in plasma are promising prognostic biomarkers, correlating with shorter progression-free survival.

Stauffer syndrome : a rare paraneoplastic complication of renal cell carcinoma to be kept in mind. Case report and literature survey.

The authors report the case of a 74-years-old woman treated by immunotherapy for a metastatic renal cell carcinoma and having developed an important cholestasis with thrombocytosis, increased CRP, leucocytosis and hypoalbuminemia. Liver remained free of metastases at medical imaging. The diagnosis of a Stauffer syndrome was confirmed by the hepatic biopsy. A complete response of liver disorders was obtained after nephrectomy. From literature survey, Stauffer syndrome should be kept in mind in cancer patients, especially those suffering from a renal cell carcinoma, presenting with cholestasis with no underlying cause.

A 42-year-old patient with renal cell carcinoma presenting as low back pain: A case report.

RATIONALE: Renal cell carcinoma (RCC) is the most common renal neoplasm, accounting for 2.4% of all cancers in Korea. Although the usual clinical manifestations of RCC include flank pain, hematuria, and palpable mass, RCC is generally characterized by a lack of early warning signs and is mostly discovered incidentally in advanced stage. This case report describes a 42-year-old Korean man diagnosed with giant RCC who presented with simple back pain. PATIENT CONCERNS: The clinical manifestation of a 42-year-old Korean man was chronic back pain. DIAGNOSES: Contrast-enhanced computed tomography showed a 19.1-cm sized heterogeneous enhancing mass on the right kidney and tumor thrombosis extending into inferior vena cava. INTERVENTION: Due to the large size of the tumor and extensive tumor thrombosis, the multidisciplinary team decided to administer neoadjuvant chemotherapy and an anticoagulant. Following 12 cycles of treatment with nivolumab and cabozantinib, he underwent a right radical nephrectomy with an adrenalectomy and tumor thrombectomy. OUTCOMES: Treatment was successful and posttreatment he started a cancer rehabilitation program. He was followed-up as an outpatient and no longer complains of back pain. LESSONS: RCC can manifest clinically as back pain, with diagnosis being difficult without appropriate imaging modalities. RCC should be included in the differential diagnosis of patients with low back pain, even at a young age.

Urine cytology in the detection of renal cell carcinomas - a territory-wide multi-institutional retrospective review of more than 2 decades.

INTRODUCTION: Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas. METHODS: Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses. RESULTS: There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p < .05). Larger lesion size and higher urine volume did not improve detection rates (p < .05). CONCLUSIONS: The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.

Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.

Renal cell carcinoma (RCC) arises from the tubular epithelial cells of the nephron. It has the highest mortality rate among urological cancers. There are no effective therapeutic approaches and no non-invasive biomarkers for diagnosis and follow-up. Thus, suitable novel biomarkers and therapeutic targets are essential for improving RCC diagnosis/prognosis and treatment. Circulating exosomes such as exosomal microRNAs (Exo-miRs) provide non-invasive prognostic/diagnostic biomarkers and valuable therapeutic targets, as they can be easily isolated and quantified and show high sensitivity and specificity. Exosomes secreted by an RCC can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a ''signature'' or ''fingerprint'' of the donor cell. It has been shown that the transportation of renal-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in RCC. The present review highlights the studies reporting tumor microenvironment-derived Exo-miRs with therapeutic potential as well as circulating Exo-miRs as potential diagnostic/prognostic biomarkers in patients with RCC.

Papillary Renal Cell Carcinoma: Evolving Classification by Combined Morphologic and Molecular Means.

Papillary renal cell carcinoma classification has evolved as a result of attentive morphologic observations by pathologists coupled with specific immunohistochemical, molecular, and clinical data. Refinement of this relatively common diagnostic category of renal neoplasia has resulted in the parsing out of specific renal cell carcinoma subtypes that no longer belong in the papillary renal cell carcinoma category and can have distinct familial and prognostic implications (eg, fumarate hydratase (FH)-deficient renal cell carcinomas). In addition, evolving classification has enabled more accurate diagnosis by surgical pathologists (through the description of recognizable morphologic variants). In many cases, molecular findings have aided and confirmed morphologic categorization. The combination of morphologic and molecular findings continues to provide important prognostic information for patients and their clinicians.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Sarcomatoid variant of Xp11 translocation renal cell carcinoma: A rare case report in an adult female.

Xp11 translocation renal cell carcinoma (XPTRCC) is a very rare kidney neoplasm, which has been predominantly reported in young patients. Sarcomatoid transformation in renal cell carcinomas is known. However, its occurrence in XPTRCC is unreported so far in the literature. We report a unique case of sarcomatoid transformation in a XPTRCC in a 23-year-old female, who presented with a huge right-sided renal mass and had metastatic deposits in lungs. Morphologically, clear cell morphology with papillary architecture along with foci of sarcomatoid transformation and rhabdoid differentiation were noted. Immunohistochemistry showed Pax-8 and TFE-3 expression in all components including the sarcomatous areas, whereas CK and EMA were expressed in conventional clear cell component. We present an extremely rare case of sarcomatous transformation in XPTRCC and discuss the case as determined by histopathology and immunocytochemistry. To our knowledge, this is the first case of sarcomatoid transformation XPTRCC being reported in the world literature.

Prognostication for surgically treated papillary renal cell carcinoma: which model is the optimal choice?

Tweetable abstract Surgically treated papillary renal cell carcinoma shows distinct prognosis and needs specific prognostic models for counseling, follow-up and high-risk patient identification. Our goal is to summarize and compare currently recommended models.

Synchronous hepatocellular carcinoma and renal cell carcinoma: A cytological marvel.

Multiple primary synchronous tumours have always created an inquisitiveness among clinicians, radiologists and pathologists. The diagnosis invariably proposes a challenge to diagnosticians. The coexistence of a primary hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) is exceedingly rare, with countable number of cases being reported in literature. We report a pioneer case of 75-year-old male, having chronic hepatitis B, diagnosed with synchronous primary RCC and HCC in by fine-needle aspiration cytology (FNAC) and confirmed by immunohistochemistry.

How to improve initial diagnostic accuracy of kidney tumours in childhood?-A non-invasive approach.

Non-invasive differentiation of paediatric kidney tumours is particularly important in the SIOP-RTSG protocols, which recommend pre-operative chemotherapy without histological confirmation. The identification of clinical and tumour-related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93-01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI-characteristics, including diffusion-weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis-based neoadjuvant treatment.

Application of Computed Tomography Scanning Parameters Combined with Serum Cripto-1 in the Diagnosis of Renal Cell Carcinoma

Objective: This study aims to analyse the clinical value of computed tomography (CT) scanning parameters combined with serum teratoma-derived growth factor-1 (Cripto-1) in the diagnosis of renal cell carcinoma (RCC). Methods: A retrospective analysis was conducted on 256 patients with renal tumour admitted to our hospital from July 2020 to December 2022. They were divided into malignant group (n = 180) and benign group (n = 76) based on the final pathological results. All subjects underwent CT scans and serum Cripto-1 testing. The CT signs and serum Cripto-1 levels of the patients were analysed, and their diagnostic efficacy was evaluated. Results: The pathological diagnosis results showed 180 cases of malignant tumours, including 73 cases of clear cell carcinoma, 60 cases of papillary RCC and 47 cases of chromophobe cell carcinoma as well as 76 cases of benign tumour, including 31 cases of renal angiomyolipoma, 25 cases of eosinophilic tumour and 20 cases of renal fibroma. The malignant group had significantly higher incidence of cystic necrosis, uneven enhancement and rapid progression than the benign group (p < 0.01). The incidence of calcification was not statistically different between the two groups (p > 0.05). The malignant group had lower CT value of focus (p < 0.01) and relative corrected CT value of the renal cortex (p < 0.05), and significantly higher serum levels of Cripto-1 (p < 0.01) than the malignant group. The area under the curve of the combined diagnosis was significantly higher than that of serum Cripto-1 alone and comprehensive diagnosis of CT parameters (pcombined diagnosis vs serum Cripto−1 < 0.001, pcombined diagnosis vs comprehensive diagnosis of CT parameters = 0.002). The sensitivity of the combined diagnosis was also higher than that of serum Cripto-1 and CT parameters alone (AU)