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Background: With the development of modern medicine and the application of multimodal treatment strategies, the survival rate after childhood malignant tumors as well as the incidence of Secondary malignant neoplasm (SMN) have increased. Case report: Patient is a Chinese girl. Initially diagnosed with Wilms tumor affecting her left kidney at the age of 6, she was later found to have TFE3 -rearranged renal cell carcinoma (rRCC) affecting her right kidney at the age of 12. Employing NGS technology on specimens obtained from the TFE3 -rRCC, we uncovered a significant somatic mutation within PRSS8 gene. This discovery sheds new light on the intricate genetic landscape underlying her condition, paving the way for further exploration and personalized treatment strategies. Conclusion: We consider that the etiology of SMN may be the result of chemoradiotherapy.

Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype-phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Elevated plasma D-dimer levels are an unfavorable prognostic indicator for various tumors. However, its predictive value for prognosis in pediatric patients with Wilms tumor (WT) remains unknown. We aimed to investigate the clinical and prognostic value of preoperative plasma D-dimer levels and other clinicopathological characteristics in patients with favorable histology WT (FHWT)., Materials and Methods: The clinical data of 74 children with FHWT from January 2010 to January 2022 were retrospectively analyzed. The clinicopathologic characteristics, preoperative laboratory parameter results, including D-dimer level, and follow-up data were collected. Based on the postoperative recovery status, the patients were divided into tumor-free survival and disease progression groups. The risk factors affecting disease progression in pediatric patients with WT and the impact of plasma D-dimer levels on overall survival (OS) were evaluated., Results: Over a median follow-up of 33 months (range: 2-145 months), 56 patients survived without progression. Relapses and metastases occurred in 18 patients, of which four survived and 14 died. Higher preoperative plasma D-dimer levels (>0.865) (Odds ratio [OR] = 7.240, 95% confidence interval (CI) = 1.276-33.272, P = 0.011) and tumor rupture (OR = 19.984, 95% CI = 1.182-338.013, P = 0.038) were independent prognostic factors for disease progression. Additionally, patients with elevated D-dimer levels demonstrated a worse 5-year OS than those with low D-dimer levels (Hazard ratio (HR) =4.278, 95% CI = 1.074-17.035, P = 0.039)., Conclusions: Elevated D-dimer levels are a prognostic factor for a poorer outcome in pediatric patients with WT and are expected to become a clinical biomarker for predicting the prognosis of WT., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Kidney cysts and tumors often are identified during imaging for unrelated issues. Kidney cysts can be attributable to heritable polycystic kidney diseases. These cysts are rare in children. In adults, they affect approximately 50% of individuals older than 50 years. Kidney cysts are categorized on imaging using the Bosniak Classification of Cystic Renal Masses, which determines the likelihood that cysts are malignant or benign. Asymptomatic Bosniak class I and II cysts require no further evaluation or follow-up; however, symptomatic large simple cysts might require treatment. Bosniak class III and IV cysts might be malignant and require excision. Kidney tumors also occur in children and adults. In children, the most common is Wilms tumor, but after age 10 years renal cell carcinoma (RCC) is more common. In adults, kidney tumors may be malignant or benign. RCC accounts for 85% of kidney tumors in adults, often with metastatic disease. In patients with kidney tumors, biopsy typically is avoided to prevent spread of malignant cells. Tumors that appear suspicious for cancer on imaging are managed directly, which can include total or partial nephrectomy, ablation therapy, and adjuvant therapies, along with chemotherapy and radiotherapy depending on tumor stage. For some patients, evaluation may involve consideration of genetic testing for hereditary cancer syndromes. Patients with these syndromes should undergo periodic screening for RCC., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Context.—: Wilms tumor (WT) in adult patients is rare and has historically been a diagnostic and therapeutic conundrum, with limited data available in the literature., Objective.—: To provide detailed diagnostic features, molecular profiling, and patient outcomes in a multi-institutional cohort of adult WT patients., Design.—: We identified and retrospectively examined 4 adult WT cases., Results.—: Two patients presented with metastatic disease, and diagnoses were made on fine-needle aspiration of their renal masses. The aspirates included malignant primitive-appearing epithelioid cells forming tubular rosettes and necrosis, and cell blocks demonstrated triphasic histology. In the remaining 2 cases, patients presented with localized disease and received a diagnosis on resection, with both patients demonstrating an epithelial-predominant morphology. Tumor cells in all cases were patchy variable positive for PAX8 and WT1 immunohistochemistry. Next-generation sequencing identified alterations previously reported in pediatric WT in 3 of 4 cases, including mutations in ASXL1 (2 of 4), WT1 (1 of 4), and the TERT promoter (1 of 4), as well as 1q gains (1 of 4); 1 case showed no alterations. Three patients were treated with pediatric chemotherapy protocols; during follow-up (range, 26-60 months), 1 patient died of disease., Conclusions.—: WT is an unexpected and difficult entity to diagnose in adults and should be considered when faced with a primitive-appearing renal or metastatic tumor. Molecular testing may help exclude other possibilities but may not be sensitive or specific because of the relatively large number of driver mutations reported in WT., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

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., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: Wilms tumor (WT) is the most common childhood kidney cancer. It is a rapid growing embryonal tumor in young children and can be diagnosed with and without tumor related symptoms., Methods: We retrospectively analyzed the route to diagnosis of WT treated prospectively according to the SIOP 93-01/GPOH and 2001/GPOH in Germany between 1993 and 2022. Four routes were defined: diagnosis due to tumor-related symptoms, incidental diagnosis during another disease, diagnosis by preventive examinations, and diagnosis within a surveillance program. For these groups we compared clinical and tumor characteristics and outcome., Results: Of 2549 patients with WT 1822 (71.5%) were diagnosed by tumor-related symptoms, 472 (18.5%) incidentally, 213 (8.4%) by preventive medical examinations, and 42 (1.6%) by surveillance. Age, general health status, tumor volume, and local and overall stage varied significantly between these groups. The youngest patients were those diagnosed by preventive medical examination (mean: 1.70 years). These patients also showed the best general health status. Tumor volume at diagnosis (549 mL) and after preoperative chemotherapy (255 mL) was significantly higher for children with tumor-related symptoms. The highest percentage of local stage I (78.6%) and the lowest percentage of metastatic disease (4.8%) was found in the surveillance group. The outcome of patients was not significantly different, with up to 19.0% relapses in the surveillance group and 3.0% deaths in the group with tumor-related symptoms., Conclusion: The route to diagnosis of WT correlates with age, general health status, tumor volume, and stage distribution, but does not impact the outcome of patients. Nonetheless, diagnosis without tumor related symptoms results in lower treatment burden and thus improved quality of life., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Wilms tumor (WT) occurring in adults is rare and even much more rarely found to coexist with pregnancy. Clinical outcome in adults is worse overall compared with pediatric patients with WT and is often misdiagnosed with no standardized protocols for care guided by high-evidence clinical trials. We present a case of a 23-year-old woman diagnosed with WT who was found to be pregnant immediately following nephrectomy. Workup findings showed that she had disseminated disease but was successfully managed in a multidisciplinary team setting with modified intrapartum chemotherapy followed by postpartum chemotherapy. In low-resource settings, management protocols for adult patients with WT can be individualized by multidisciplinary teams to leverage available resources for best outcomes., (© 2023 International Federation of Gynecology and Obstetrics.)

Wilms tumor (WT) is the commonest cause of renal cancer in children. In Europe, a diagnosis is made for most cases on typical clinical and radiological findings, prior to pre-operative chemotherapy. Here, we describe a case of a young boy presenting with a large abdominal tumor, associated with raised serum alpha-fetoprotein (AFP) levels at diagnosis. Given the atypical features present, a biopsy was taken, and histology was consistent with WT, showing triphasic WT, with epithelial, stromal, and blastemal elements present, and positive WT1 and CD56 immunohistochemical staining. During pre-operative chemotherapy, serial serum AFP measurements showed further increases, despite a radiological response, before a subsequent fall to normal following nephrectomy. The resection specimen was comprised of ~55% and ~45% stromal and epithelial elements, respectively, with no anaplasia, but immunohistochemistry using AFP staining revealed positive mucinous intestinal epithelium, consistent with the serum AFP observations. The lack of correlation between tumor response and serum AFP levels in this case highlights a more general clinical unmet need to identify WT-specific circulating tumor markers., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Renal cell carcinoma is uncommon in children and must be distinguished from the more common Wilms' tumor. Here, we present two cases of renal cell carcinoma in children both of whom presented with hematuria. Accurate diagnosis is essential in order to differentiate it from epithelial predominant Wilms' tumor which has vastly different prognosis and treatment. Immunohistochemistry for TFE3 is useful in establishing the diagnosis., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Abstract: A 19-year-old woman presented with painless lower abdominal discomfort and a cystic-solid mass measuring 15.9 cm on the right ovary. She subsequently underwent laparoscopic right ovarian cystectomy. Microscopic examination of the mass showed the typical morphological features of Wilms' tumor and the predominance of teratoid elements constituting more than 50% of the tumor. To date, few cases of extrarenal teratoid Wilms' tumor (TWTs) in adults have been reported in the literature. The case presented in the present is the third reported case of adult extrarenal TWT occurring in ovary., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Accurate diagnosis of neuroblastoma may be challenging, especially with limited or inadequate specimen and at the metastatic sites due to overlapping imaging, histopathologic, and immunohistochemical (immunohistochemistry [IHC]; infidelity among various lineage-associated transcription factors eg FLI1, transducin-like enhancer 1, etc) features. GATA3 and ISL1 have recently been described as markers of neuroblastic differentiation. This study aims at determining the diagnostic utility of GATA3 and ISL1 in differentiating neuroblastoma from other pediatric malignant small round blue cell tumors., We evaluated GATA3 and ISL1 expression in 74 pediatric small round blue cell tumors that included 23 NMYC -amplified neuroblastomas, 11 EWSR1 -rearranged round cell sarcomas, 7 SYT::SSX1 -rearranged synovial sarcomas, 5 embryonal rhabdomyosarcomas, 10 Wilms tumors (nephroblastomas), 7 lymphoblastic lymphoma, 7 medulloblastoma, and 4 desmoplastic small round cell tumor., All 23 neuroblastomas (moderate to strong staining in >50% of the tumor cells), 5 T-lymphoblastic lymphomas (moderate to strong staining in 40%-90% of the tumor cells), and 2 desmoplastic small round cell tumors (weak to moderate staining in 20%-30% of the tumor cells) expressed GATA3, while other tumors were negative. ISL1 immunoreactivity was observed in 22 (96%) neuroblastomas (strong staining in in >50% of the tumor cells, n  =  17; moderate to strong staining in 26%-50% of the tumor cells, n  =  5), 3 embryonal rhabdomyosarcoma (moderate to strong staining in 30%-85% of the tumor cells), 1 synovial sarcoma (weak staining in 20% of the tumor cells), and 7 medulloblastoma (strong staining in 60%-90% of the tumor cells). Other tumors were negative. Overall, GATA3 showed 86% specificity, 100% sensitivity, and 90% accuracy for neuroblastoma, with a positive predictive value (PPV) and negative predictive value (NPV) of 77% and 100%, respectively. ISLI showed 72% specificity, 96% sensitivity, and 81% accuracy for neuroblastoma, with a PPV and NPV of 67% and 97%, respectively. After the exclusion of T-lymphoblastic lymphoma and desmoplastic small round cell tumors, GATA3 had 100% specificity, sensitivity, accuracy, and PPV and NPV for neuroblastoma. Similarly, in pediatric small round blue cell tumors, ISL1 had 100% specificity, sensitivity, accuracy, PPV, and NPV for neuroblastoma, after embryonal rhabdomyosarcoma, synovial sarcoma, and medulloblastoma were excluded., Conclusions: GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Delays in diagnosis and time to diagnosis generally are used interchangeably in cancer disparity research, but these terms may have important differences. Although these terms are related, we hypothesize that time to diagnosis is determined by the aggressiveness of the tumor based on intrinsic factors such as tumor biology, whereas delays in diagnosis are caused by extrinsic factors such as socioeconomic status, leading to presentation at higher stage of disease due to barriers of care. We conducted a retrospective study of 306 patients diagnosed with Wilms tumor at Children's Hospital Colorado between 1971 and 2016 identifying patient barriers as extrinsic markers and using unfavorable histology and loss of heterozygosity as markers of aggressive tumor biology. Multivariable logistic regression was performed. Patients with Medicaid were more likely to present greater than 4 days after initial symptoms compared to those with private insurance, and those with housing concerns were more likely to be diagnosed greater than 9 days from initial symptoms. Tumor biology was noted to be associated with higher stage at diagnosis, but patient barriers were not. These findings suggest the interplay between tumor biology, patient barriers, diagnostic timing, and stage at diagnosis is more complex, multifactorial, and in need of further study., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.

Wilms tumor (WT) represents over 90% of all pediatric kidney tumors. Children with WT often present acutely with hypertension which resolves in the short term after nephrectomy. However, WT survivors have increased long-term risk of hypertension, primarily due to decreased nephron mass after nephrectomy, with additional insults from possible exposure to abdominal radiation and nephrotoxic therapies. The diagnosis of hypertension may be improved by ambulatory blood pressure monitoring (ABPM), as several recent single-center studies have shown a substantial proportion of WT survivors with masked hypertension. Current gaps in knowledge include determining which WT patients may benefit from routine screening with ABPM, correlation of casual and ABPM parameters with cardiac abnormalities, and longitudinal assessment of cardiovascular and kidney parameters in relation to appropriate treatment of hypertension. This review aims to summarize the most recent literature on hypertension presentation and management at the time of WT diagnosis as well as the long-term hypertension risk and impact on kidney and cardiovascular outcomes in WT survivors., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: Wilms tumor (WT) and Rhabdoid tumor (RT) are pediatric renal tumors and their differentiation is based on histopathological and molecular analysis. The present study aimed to introduce the panels of mRNAs and microRNAs involved in the pathogenesis of these cancers using deep learning algorithms. Methods: Filter, graph, and association rule mining algorithms were applied to the mRNAs/microRNAs data. Results: Candidate miRNAs and mRNAs with high accuracy (AUC: 97%/93% and 94%/97%, respectively) could differentiate the WT and RT classes in training and test data. Let-7a-2 and C19orf24 were identified in the WT, while miR-199b and RP1-3E10.2 were detected in the RT by analysis of Association Rule Mining. Conclusion: The application of the machine learning methods could identify mRNA/miRNA patterns to discriminate WT from RT. The identified miRNAs/mRNAs panels could offer novel insights into the underlying molecular mechanisms that are responsible for the initiation and development of these cancers. They may provide further insight into the pathogenesis, prognosis, diagnosis, and molecular-targeted therapy in pediatric renal tumors.

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Germ cell tumors primarily arise in gonads and extragonadal germ cell tumors, an uncommon entity, originates usually along the midline. Here, we report the fifth example of intrarenal pure yolk sac tumor in a 1.5-year-old boy who presented with abdominal pain and underwent excision of the mass for suspected Wilms tumor. On histopathology and immunohistochemistry, a diagnosis of a yolk sac tumor was rendered. Postoperative serum alpha-fetoprotein levels were 21 000 ng/dl. The purpose of this report is to emphasize the importance of suspecting a germ cell tumor as one of the differential diagnoses of a suspected case of Wilms tumor and the significance of evaluating serum alpha-fetoprotein levels preoperatively., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or Wilms tumor. This study aims to determine the immunohistochemical expression of P53 protein and its predictors in formalin-fixed paraffin-embedded tissue blocks of patients with nephroblastoma., Materials and Methods: A series of 83 histologically diagnosed cases of nephroblastoma from formalin-fixed paraffin-embedded tissue blocks archived at the Department of Pathology, Makerere University, in Kampala, Uganda, were analyzed. Monoclonal anti-p53 antibody (DO-7, DAKO) was used to assess the expression of P53 protein expression. Multivariable logistic regression analysis was performed to determine the predictors of P53 protein immunohistochemical expression, and statistical significance was considered when p-value was less than 0.05., Results: Most (42.2%, n = 35) of the cases were in advanced tumor stages (III-V), and almost one-quarter (21.7%, n = 18) of the cases were in high-risk group. The immunohistochemical expression of P53 protein was (8.4%, n = 7), and there were more (83.3%, n = 5) positive anaplastic cases for P53 protein compared with (2.6%, n = 2) of P53 expression for non-anaplastic cases. High risk (AOR = 3.42, 95% CI = 7.91-12.55, p = 0.037) and anaplasia (AOR = 1.41, 95% CI = 13.85-4.46, p = 0.001) were potential predictors of immunohistochemical expression of P53 protein., Conclusion: Most of patients with nephroblastoma in resources-limited settings are diagnosed with advanced clinical stages. Association of P53 protein with anaplasia found in this study indicates the possibility of having novel target therapy for treatment of patients with anaplastic form of nephroblastoma with a focus of identifying molecules that lead to its suppression in such subpopulations of patients with nephroblastoma., (© 2023. The Author(s).)

Background: Yolk sac tumor is a germ cell tumor (GCT) that occurs in infants and adolescents and affects various sites. There is a trend to treat pediatric renal tumors before a tissue diagnosis. We report a renal yolk sac tumor clinically misdiagnosed as Wilms tumor, based on ultrasound (US) and MRI. Case Report: This 21-month-old male infant was discovered to have a space occupying lesion in the right kidney. Because the tumor was large, initial radiotherapy preceded surgical resection. Histologically, the tumor was a yolk sac tumor. Conclusion: Imaging examination of renal yolk sac tumor can easily be misdiagnosed as Wilms tumor. SIOP treatment plan for Wilms tumor requires preoperative chemotherapy, which is different from the treatment regimen for yolk sac tumor. Preoperative alpha-fetoprotein could have been helpful in avoiding this clinical misdiagnosis.

Wilms' tumor (WT) is the most common renal malignancy in children. In diffuse hyperplastic perilobar nephroblastomatosis (DHPLN), nephrogenic rests result in a bulky enlargement of the kidney, a condition considered as a premalignant state before WT. Despite relevant clinical differences between WT and DHPLN, they are often challenging to distinguish based on histology. Molecular markers would improve differential diagnosis, but none are available at present. In our study, we investigated the potential of microRNAs (miRNAs) as such biomarkers, also aiming to shed light on the chronological order of expression changes. Formalin-fixed, paraffin-embedded (FFPE) samples from four DHPLN cases and adjacent healthy tissues were tested using a PCR array containing primers for 84 miRNAs implicated in genitourinary cancer. Expression in DHPLN was compared to WT data available in dbDEMC. Let-7, miR-135, miR-146a-5p, miR-182-5p, miR-183-5p, miR-20b-3p, miR-29b-3p, miR-195-5p and miR-17-5p showed potential to be used as biomarkers to distinguish WT and DHPLN in cases when traditional differential diagnosis is inconclusive. Our study also revealed miRNAs which may play a role in the initial steps of the pathogenesis (at a precancerous stage) and ones which become deregulated later in WT. More experiments are needed to confirm our observations and find new candidate markers.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction Although nephroblastomas are frequently treated without prior biopsy, there are the occasional other pediatric renal tumors that require different management. In the literature, there are around 30 primary renal germ cell tumors (GCT), including four cases of Yolk sac tumor (YST). We present another primary renal YST. Case report: A five-year-old boy was diagnosed as Wilms tumor on radiology and needle biopsy. He received chemotherapy, with no response. The post-chemotherapy resection specimen revealed a YST. Conclusion: Renal YST may be indistinguishable from Wilms tumor clinically and radiologically. For pre-biopsy chemotherapy management protocols, serum tumor markers such as AFP may be recommended to identify the occasional GCT, including YST. Pre-chemotherapy needle biopsies may lead to misdiagnosis, and may require confirmation by an experienced pathologist or central review.

Objectives: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center., Patients and Methods: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted., Results: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis., Conclusion: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Clinical/methodical Issue: The Beckwith-Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys-Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of developing chronic kidney disease and bilateral and metachronous tumors as well as nephrogenic rests., Standard Radiological Methods: Standard imaging diagnostics for WT include renal ultrasound and magnetic resonance imaging (MRI). In the current renal tumor studies Umbrella SIOP-RTSG 2016 and Randomet 2017, thoracic computed tomography (CT) is also recommended as standard. Positron emission tomography (PET)-CT and whole-body MRI, on the other hand, are not part of routine diagnostics., Methodological Innovations: In recent publications, renal ultrasound is recommended every 3 months until the age of 7 years in cases of clinical suspicion or molecularly proven TPS., Performance: Patients with TPS and regular renal ultrasounds have smaller tumor volumes and lower tumor stages at WT diagnosis than patients without such a screening. This allows a reduction of therapy intensity and facilitates the performance of nephron sparing surgery, which is prognostically relevant especially in bilateral WT., Achievements: Early diagnosis of WT in the context of TPS ensures the greatest possible preservation of healthy and functional renal tissue. Standardized screening by regular renal ultrasounds should therefore be firmly established in clinical practice., Practical Recommendations: The initial diagnosis of TPS is clinical and requires a skilled and attentive examiner in the presence of sometimes subtle clinical manifestations, especially in the case of BWSp. Clinical diagnosis should be followed by genetic testing, which should then be followed by sonographic screening., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

To designate the probable most important differentially expressed genes and genetic pathways in Wilms tumor and assess their expression and diagnostic potential by RT-PCR and statistical analysis. Systematic review of the literature and various bioinformatics analysis was carried out to gather and narrow down data. The expression of end-resulting genes was compared in Wilms tumor and normal tissue samples using RT-PCR. Statistical tests reported the diagnostic accuracy of genes and their correlation with clinicopathological features. Four genes including CDH1, NCAM1, EGF, and IGF2 were designated. The panel combining them has 100% sensitivity and specificity in differentiating tumors from normal tissue. Eight pathways, most involved in cell-cell and cell-basal matrix junction interactions, were found to be associated with disease pathogenesis. The suggested genes should undergo further evaluation to be validated as diagnostic biomarkers. Further research on the eight proposed pathways is recommended., (© 2022. The Author(s).)

Rare benign tumours of the kidney comprise a group of very different histogenetic entities. We report a case of a 53-year-old woman who underwent laparoscopic nephrectomy because of a renal mass. The diagnosis of a rare and benign metanephric adenoma was confirmed by histopathology. With less than 200 documented cases, the metanephric adenoma described here is a rarity in everyday urological practice and cannot be distinguished from a malignant tumour of the kidney by clinical examination and/or imaging without histological assessment., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Pediatric small round blue cell tumors (PSRBCT) are an intriguing and challenging collection of neoplasms. Light microscopy of small round blue cell tumors identifies small round cells. They harbor a generally hyperchromatic nucleus and relatively scanty basophilic cytoplasm. Pediatric small round blue cell tumors include several entities. Usually, they incorporate Wilms tumor, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, retinoblastoma, lymphoma, and small cell osteosarcoma, among others. Even using immunohistochemistry, the differential diagnosis of these neoplasms may be controversial at light microscopy. A faint staining or an ambiguous background can deter pathologists from making the proper diagnostic decision. In addition, molecular biology may provide an overwhelming amount of data challenging to distinguish them, and some translocations may be seen in more than one category. Thus, transmission electron microscopy (TEM) can be extremely valuable. Here we emphasize the modern protocol for TEM data of the neuroblastoma. Tumor cells with tangles of cytoplasmic processes containing neurosecretory granules can diagnose neuroblastoma.

Background: Pediatric non-Wilms renal tumors (NWRTs), which comprise a small proportion of renal tumors, are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment. We performed this study to determine the clinical characteristics, management and prognosis of children with Pediatric NWRTs., Methods: Medical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01-2019.10) at a single center were reviewed retrospectively., Results: The histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney (MRTK) (n: 30, 21.6%), renal cell cancer (RCC) (n: 26,18.7%), clear cell sarcoma of the kidney (CCSK) (n: 24,17.3%), congenital mesoblastic nephroma (CMN) (n: 21,15.1%), cystic nephroma (CN) (n: 16,11.5%), metanephric tumors (n: 12, 8.6%), renal angiomyoliporma (RAML) (n: 3, 2.2%), renal primitive neuroectodermal tumor (n: 2, 1.4%), renal hemangioma (n: 2, 1.4%), inflammatory myofibroblastic tumor (n: 2, 1.4%), ossifying renal tumor of infancy (ORTI) (n: 1, 0.7%). The distribution of all malignant NWRTs, including MRTK, CCSK, RCC and PNET, according to stage was as follows: stages I (n = 26), II (n = 16), III (n = 29), and IV (n = 11). The summary table shows the treatment offered to children with NWRTs. A total of 123 children were followed up for an average of 42 months. Sixteen children were lost to follow-up. Tumor-free survival was observed in 94 children. One patient who suffered from RCC is currently receiving targeted therapy and survives with the tumor. Twenty-eight children (22.8%) died., Conclusions: Pediatric NWRTs comprise 19.1% of all renal tumors in our single center. Most NWRTs can readily be distinguished using a range of immunohistochemical markers. Molecular genetic profiling has allowed much progress in the understanding of this group of tumors, making diagnosis and classification less difficult. The mainstay treatment of malignant NWRTs, including MRTK, CCSK, RCC and PNET, is comprehensive treatment. The mainstay treatment of benign NWRTs, including RAML, CN, ORTI, CMN, metanephric tumors, and renal hemangioma, is surgical resection alone and when the tumor diameter is smaller than 7 cm and the tumor locates in one pole, NSS can be performed., (© 2022. The Author(s).)

Metanephric adenoma (MA) and Wilms tumor (WT) represent 2 prototypes of primary renal neoplasms closely resembling embryonal renal tubules. Tumors with overlapping features may occur, requiring differential diagnoses between the 2. Evidence of divergent oncogenic pathways has been reported, suggesting that MA is driven by BRAF mutation while most WT is of the BRAF wild-type. We collected 4 MA cases, 3 cases of monophasic epithelial WT, and 1 overlap metanephric tumor that contains both conventional MA and high-grade components similar to epithelial WT. Whole-exome sequencing and whole transcriptome sequencing were performed to discover mutations, somatic copy number variation, and differential expression. The findings were compared with those of WT of the TARGET database (WT-TARGET). BRAF V600E mutation was detected in all MAs as well as the overlap tumor but was undetectable in all epithelial WTs and WT-TARGET. The overlap tumor showed an additional pathogenic mutation of SETD2. Three frequent gene mutations observed in WT-TARGET were not common in epithelial WT, in which the mutations appeared sporadic. The profiles of recurrent copy number variations were all different among MA, epithelial WT, and WT-TARGET. Differential expression and unsupervised hierarchical cluster analyses revealed distinct clusters of the 3 categories. Remarkably, the overlap tumor coclustered with MA, separated from epithelial WT and WT-TARGET. The distinctiveness of MA and WT were demonstrated corresponding to BRAF-mutated and non-BRAF-mutated pathways from the molecular perspective. BRAF assay has diagnostic implication for overlap tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Pediatric renal tumors overlap histomorphologically and may cause misdiagnosis. We aimed to determine the role of immunohistochemical staining of Cyclin D1, PTEN, beta-catenin and PDGFR-alpha on pediatric renal tumors., Material and Method: Thirty-six cases of 8 different tumors were included in the study. Four blocks of paraffin tissue microarray were constructed. Cyclin D1, PTEN, beta-catenin and PDGFR-alpha were used in all cases. Staining intensity and extent were graded., Results: All cases of clear cell sarcoma (CCS) and epithelial components of Wilms tumor (WT) showed immunopositivity for Cyclin D1 but blastemal and stromal components of WT were negative. All cases of CCS and most cases of WT consisting of blastemal and stromal components demonstrated loss of expression with PTEN., Conclusion: Cyclin D1 is not a specific immunohistochemical marker due to its strong and diffuse positivity in CCS cases. It may be useful to differentiate CCS from blastemal and stromal components of WT. Other markers except cyclin D1 do not have a role in the differential diagnosis.

Context or Background: Pediatric renal tumours are the second most common solid tumours in children. The most common in this group is Wilms tumour with mesoblastic nephroma being the 2 nd most common tumour in children, younger than 3 months., Aims and Objectives: The present study was conducted to study the epidemiological occurrence of pediatric renal tumours at a tertiary care hospital and to study the diagnostic efficacy of WT1 immunostaining in distinguishing Wilms tumour from other types of renal tumours., Materials and Methods: It was a single institution-based prospective and observational study conducted for 2 years (from October 2013 to September 2015) in the department of pathology in our hospital. A total of 50 cases were enrolled in this study all were below 15 years of age., Results: Nephroblastoma or Wilms tumour was found to be the most common type, occurring in 66% cases. Fourteen out of 33 cases of Wilms tumour showed triphasic components (blastemal, epithelial, and stromal) with Blastemal type Wilms being the second most common (11 cases). WT1 immunostaining was positive in 93.9% cases of nephroblastoma. The highest amount of nuclear positivity noted in blastemal cells followed by epithelial cells. Rhabdomyoblastic differentiation and regressive variant showed nonspecific cytoplasmic staining. Cystic partially differentiated nephroblastoma and diffuse anaplasia type Wilms tumour showed nuclear staining in blastemal cells., Conclusion: The expression of WT1 immunostain was found to be diagnostically significant in differentiating Wilms tumour from other renal tumours., Competing Interests: None

Background: Wilms Tumor (WT) is the most common primary renal malignancy in children. Autophagy plays dual roles in the promotion and suppression of various cancers., Objective: The goal of our study was to develop a novel autophagy-related gene (ARG) prognostic nomogram for WT., Methods: The Cancer Genome Atlas (TCGA) database was used. We screened the expression profiles of ARGs in 136 WT patients. The differentially expressed prognostic ARGs were evaluated by multivariate Cox regression analysis and survival analysis. A novel prognostic nomogram based on the ARGs and clinical characteristics was established using multivariate Cox regression analysis., Results: First, 69 differentially expressed ARGs were identified in WT patients. Then, multivariate Cox regression analysis was used to determine 4 key prognostic ARGs (CC3CL1, ERBB2, HIF-α and CXCR4) in WT. According to their ARG expression levels, the patients were clustered into high- and low-risk groups. Next, survival analysis indicated that high-risk patients had significantly poorer overall survival than low-risk patients. The results of functional enrichment analysis suggested that autophagy may play a tumor-suppressive role in the initiation of WT. Finally, a prognostic nomogram with a Harrell's concordance index (C-index) of 0.841 was used to predict the survival probability of WT patients by integrating clinical characteristics and the 4-ARG signature. The calibration curve indicated its excellent predictive performance., Conclusion: In summary, the ARG signature could be a promising biomarker for monitoring the outcomes of WT. We established a novel nomogram based on the ARG signature, which accurately predicts the overall survival of WT patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Compare to congenital mesoblastic nephroma in fetus, congenital wilms tumor is extremely rare. Herein we report a case of congenital bilateral solid masses on antenatal ultrasound. The mass was evaluated by ultrasonography and contrast computed tomography scan in postnatal period, and the patient was undergoing tumor enucleation separately in short period after neoadjuvant chemotherapy. The diagnosis was confirmed by histology analysis for each side, and the treatment was taken according to the International Society of Pediatric Oncology., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aim: Clear cell sarcoma of kidney (CCSK) is the second most common pediatric renal malignancy, constituting ∼3% of renal tumors. Due to its morphologic diversity, the diagnosis of CCSK is often challenging. Recent studies have identified internal tandem duplication of BCL6 corepressor (BCOR) gene in CCSKs which coupled with cyclin D1 immunoreactivity, is helpful in differentiating it from its mimics, particularly blastema-rich Wilms tumor (WT), malignant rhabdoid tumor (MRT), and congenital mesoblastic nephroma (CMN). We aimed to evaluate the utility of cyclin D1 and BCOR immunohistochemistry in differentiating CCSK from its morphologic mimics., Materials and Methods: Our cohort comprised of 38 pediatric renal tumors which included CCSK (n=18), WT (n=10), MRT (n=5), and CMN (n=5) cases. A detailed clinicopathologic analysis was performed, and tissue microarray were constructed for CCSK and WT, while MRT and CMN tumors were individually stained., Results: The age ranged from 2 months to 16 years with male:female ratio of 3:1. Strong, diffuse nuclear immunoreactivity for cyclin D1 and BCOR was noted in 61% (n=11/18) and 83% (n=15/18) of CCSK, respectively, while it was significantly less in WT (n=3/10 for cyclin D1) (n=2/10 for BCOR). None of the MRT and CMN examples demonstrated any immunoreactivity. Interestingly, only the blastemal component of WTs showed distinct, rare nuclear immunoreactivity for cyclin D1 or BCOR and the combination of these was never positive in a given case., Conclusion: Our results provide evidence that concurrent immunopositivity with cyclin D1 and BCOR is helpful in distinguishing CCSK from its morphologic mimics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research., (© 2021. Springer Nature Limited.)