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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.)

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.)

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.)

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' tumor (WT) is the most common renal malignancy in children. Its clinical and radiologic presentation may mimic other pediatric renal diseases, including pyonephrosis or renal abscess. The authors report a case of a 3-year-old girl presenting with pyelonephritis and right renal mass suggestive of a renal abscess, not responding to antibiotics. Further investigations were conducted, including a percutaneous renal needle core biopsy. A stage I fully necrotic WT was finally diagnosed. This amazing case of a fully necrotic WT at diagnosis demonstrates the importance of anatomopathologic analyses in pediatric renal masses, even when the infection is suspected., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Cancer is diagnosed in 1 in 7000 children annually. Here, we report 6 cases of a mass identified by the author, a novice sonographer in a pediatric emergency medicine fellowship, using point-of-care ultrasound, from January of 2017 to May of 2018. Identification of these cases early in presentation allowed for earlier involvement of the relevant specialist and shorter time to diagnosis and treatment, and might be expected to increase parent satisfaction as well.

Primary extrarenal Wilms tumor of the gynecologic tract is extremely rare with scattered case reports occurring in the ovary, uterine corpus and cervix. Only 9 cases of primary ovarian Wilms tumor have been reported to date. Here, we provide an extensive literature review and describe 2 patients with ovarian Wilms tumor: a 36-yr-old female (patient 1) and a 16-yr-old female (patient 2), both presenting with abdominal pain and suspected ovarian torsion. They were each found to have unilateral ovarian masses measuring >15 cm in size which were removed by unilateral salpingo-oophorectomy. Microscopically, the tumors exhibited the typical triphasic histology of Wilms tumor. In addition, the tumor from patient 1 contained elements of mature cystic teratoma, while an extensive rhabdomyosarcomatous component was identified in patient 2. Both tumors were diffusely and strongly positive for WT1 with variable staining for other biomarkers. The cases were diagnostically challenging and referred to our center for an expert opinion. Teratoid Wilms tumor in patient 1 is the second reported case of ovarian Wilms tumor arising in association with teratoma. Recognition of primary ovarian Wilms tumor requires a high index of suspicion and exclusion of other entities based on tumor morphology and immunohistochemical studies.

Wilms tumor (WT) is an uncommon malignant neoplasm that occurs predominantly in the kidney of pediatric patients; its extrarenal counterpart is exceedingly rare. We present the case of an adult female diagnosed with uterine WT. Following hysterectomy due to a uterine mass, histopathologic examination demonstrated a triphasic malignancy composed of epithelial, stromal, and blastemal elements. The characteristic morphologic features, which were supported by immunohistochemical analysis, were diagnostic of WT of the uterus. A summary of the main clinicopathologic parameters, along with a review of all previously reported cases, are described.

This study aims to investigate the management of Wilms tumor by the Egyptian pediatric surgical association (EPSA) consultants. After approval of the EPSA executive board, a questionnaire was distributed individually to all consultants attending the general assembly of EPSA 2017 annual congress. Of 88 consultants, responses were received from 61. Palpable abdominal mass was indicated by 72.13% of respondents as the commonest presenting symptom. Concerning the imaging requested, computed tomography was reported by 80.33%. Approximately 62.30% of respondents perform 1 to 3 cases annually. Regarding timing of surgery, upfront resection was the most frequently reported by 62.30%. A total of 77.05% perform lymph node sampling during surgeries. Nephron-sparing surgery was adopted by only 26.23%, whereas none of the respondents reported the use of minimally invasive surgery for management. Overall, 93.44% of surgeons ask for a visit every 3 months in the first year postoperatively. Upfront nephrectomy is the commonest procedure for Wilms tumor in the current practice of EPSA consultants, whereas there is consensus against minimally invasive surgery. Surgical guidelines for nephron-sparing surgery are still incomplete and need to be tabulated. This study urges for a nationwide retrospective analysis to establish a uniform protocol with international reference to be adopted in Egypt.

We demonstrate a 4-year-old girl who presented with progressive, asymmetrical, firm abdominal distention and was diagnosed with synchronous Wilms' tumor and left para-aortic ganglioneuroma (GN). Although synchronous tumors in the pediatric population are commonly associated with malignancy-predisposing syndromes, the patient in question was found to be otherwise healthy and had no clinical evidence nor family history of a syndrome. This case is the second one in the literature diagnosed with synchronous presentation of Wilms' tumor and GN in a previously healthy child. In addition, a GN foci presumed to be a previous metastasis of a neurogenic tumor that subsequently matured to GN was depicted within a left para-aortic lymph node. We aimed to emphasize an extremely rare synchronous occurrence of these embryonal tumors, increase the awareness of physicians, and discuss the radiologic differential diagnosis and management.

Objective: Cancer mortality is a leading cause of disease-related death in the adolescent and young adult (AYA) population. Compared with older and younger patients, AYA patients often experience worse cancer-specific outcomes. Here, we compare AYA and pediatric overall survival (OS) in the most common pediatric extracranial solid tumors., Materials and Methods: Using the US Surveillance, Epidemiology, and End Results database, we studied patients (age, 0 to 39 y) diagnosed with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and Wilms tumor., Results: A total of 12,375 patients (age, 0 to 39 y) were diagnosed between 1973 and 2010 (8247 pediatric and 4128 AYA patients). AYA patients with rhabdomyosarcoma and Ewing sarcoma were more likely to present with metastatic disease. OS was significantly worse in the AYA cohort for all tumor types (P<0.001) with the exception of osteosarcoma (P=0.29). Across 2 treatment time periods (1973 to 1989 and 1990 to 2010), there was significant improvement in 5-year OS in all tumor types with the exception of rhabdomyosarcoma; however, AYA patients continued to experience worse OS in the modern treatment cohort with the exception of osteosarcoma patients. There was no improvement in OS among AYA patients with Ewing sarcoma, neuroblastoma, rhabdomyosarcoma, or Wilms tumor over the 2 treatment eras., Conclusions: For the most common pediatric extracranial solid tumors, AYA patients experience significantly worse OS compared with pediatric patients. Although improvements in therapy have led to gain in survival for pediatric patients, with the exception of osteosarcoma, AYA experienced no increase in survival over the study period. This investigation demonstrates the importance for further research in the AYA population.

The Beckwith-Wiedemann syndrome is a cancer predisposition syndrome characterized by a predilection to embryonal tumor growth, especially Wilms tumor, adrenocortical carcinomas, and hepatoblastomas. Genetic analysis of patients has revealed a link to the imprinted domain of the 11p15.5 chromosome and methylation status of the H19 locus and Igf-2. These genes have also been studied in other cancers, including ovarian teratomas. Our case is a patient with a simultaneous presentation of a Wilms tumor and immature ovarian teratoma and subsequently diagnosed with Beckwith-Wiedemann syndrome, which has not been previously described.

It is unclear if lymph node sampling in Wilms tumour, though critical for staging purposes, affects survival outcomes. The value of lymph node sampling in patients treated with neoadjuvant chemotherapy (NAC) is even more uncertain. We reviewed our institutional data to determine the impact of lymph node sampling on survival, as well as its role in the context of NAC. A total of 185 patients with Wilms tumour treated at our institution were included in this analysis. The number of nodes sampled (≤7, or >7), lymph node status (unknown, negative, or positive), pathological stage, and use of neoadjuvant chemotherapy were analysed for survival outcomes. Covariates were evaluated with chi-square test or Fisher's exact test where appropriate. All analyses were performed using SAS 9.3 and R package version 2.15.2 with a significant level of 0.05. Median follow-up for all patients was 7.1 years. The number of lymph nodes sampled was significantly related to lymph node status (p<0.001). Lymph node involvement portended worse overall survival after controlling for stage and histology. Patients treated with NAC had higher rates of 'unknown' lymph node status (p<0.001) and worse overall survival than their counterparts (p=0.002); within this group, patients with 'unknown' lymph node status had significantly worse survival than those with negative or positive lymph node. Our data support the available evidence that sampling of more than seven lymph nodes is necessary for adequate staging of Wilms tumour. This is especially critical in patients treated with NAC, who had worse overall survival, likely due to understaging and undertreatment. These findings should be confirmed prospectively to provide proper guidelines to physicians caring for patients with Wilms tumour., (Copyright © 2016. Published by Elsevier B.V.)

The authors report the case of a 7-month-old girl with unilateral Wilms tumor with dilated cardiomyopathy, leading to cardiac failure and requiring intensive care. After chemotherapy and tumor removal, cardiac function has improved. This is a rare report on the association between nephroblastoma and dilated cardiomyopathy without hypertension.

Renal inflammatory myofibroblastic tumor (IMT) is an extremely rare lesion especially in children. This report describes a case of renal IMT accompanied by multiple lung nodules mimicking Wilms tumor with lung metastasis in a 3-year-old boy. To our knowledge, this is a unique case of IMT which has not been reported in the literature previously.

Pediatric tumors are heterogenous and can be quite varied in appearance. However, those in the infamous "small round blue-cell tumor" group, with their hyperchromatic nuclei and small amount of cytoplasm can be challenging, and their diagnosis and prognostication require cost-efficient and focused immunohistochemistry and ancillary testing. Ideally, ample material should be obtained for routine histology and ancillary testing, including immunohistochemistry, fluorescent in situ hybridization, fresh tissue for cytogenetic studies, and snap-frozen tumor for DNA/RNA extraction both for routine molecular testing (ie, reverse-transcription PCR studies), as well as future research study protocols (genome wide studies, targeted gene sequencing). This review focuses on the main pediatric tumors with emphasis on immunophenotype, keeping in mind that a directed panel approach yields the highest yield with combination of clinical history, histologic features, and ancillary molecular testing.

Magnetic resonance imaging (MRI) has become the principal tool for Wilms tumor (WT) assessment and follow-up. MRI and histopathologic findings were not congruent in 2 of the q30 scanned patients with renal masses (2008 to 2011). Three lesions thought to be WT on MRI were found to be a sclerotic nephrogenic rest (1), cystic renal dysplasia (1), and focal chronic pyelonephritis (1). The "typical" features suggesting nephroblastomatosis and WT on MRI are unreliable and such lesions require biopsy for histopathologic diagnosis, especially when nephron-sparing surgery is necessary to preserve renal function.

Paraneoplastic syndromes may affect the central and peripheral nervous system of adults and children with cancer. Neurological symptoms may resolve with treatment of the underlying neoplasm. We report the case of a child with Wilms tumor who presented with generalized weakness, fatigue, ptosis, hypokinesis, dysarthria, urinary retention, facial diplegia, ophthalmoplegia, and autonomic dysfunction. Routine electrodiagnostic testing, including repetitive nerve stimulation, was normal. Clinical features and stimulation single-fiber electromyogram were consistent with a neuromuscular junction transmission disorder, likely Lambert-Eaton myasthenic syndrome. The child's neurological status returned to normal with successful treatment of the tumor.

Wilms tumor has a survival rate of 85% to 90% in well-resourced countries. Malawi is a country in Sub-Saharan Africa with very limited resources. We evaluated the outcome of a treatment guideline including preoperative chemotherapy, supportive care, and strategies to enable parents to complete treatment. Between 2006 and 2011, 95 patients were initially diagnosed with a Wilms tumor; 11 were later excluded due to misdiagnosis. In 31% of patients, metastases were detected at presentation. Treatment outcomes in 8 patients with bilateral tumors and 3 patients who were referred after nephrectomy are analyzed separately. Treatment failed in 51% of 73 remaining patients. Reasons for failure were: 1) incomplete treatment (7%); 2) treatment-related deaths (15%); and 3) disease-related deaths (28%) with 11% unresectable tumors or metastases after preoperative chemotherapy and 17% relapse of disease. Projected survival is 46%. Challenges remain to improve survival for children with Wilms tumor in Malawi. Earlier diagnosis would reduce disease-related deaths as numbers of unresectable disease and relapse are high. Effective strategies, including social support, to enable parents to complete treatment need to be continued. Improved supportive care and nutritional support and possibly less intense preoperative chemotherapy are needed to reduce treatment-related deaths.

Very low risk Wilms tumor is defined by favorable histology, age below 2 years, tumor weight less than 550 g, and stage I. The Children's Oncology Group is currently studying a nephrectomy-only strategy for these patients but the accrual rate is slightly below expected. Twenty-five of 31 institutions responded with reasons by physicians and/or parents for electing not to participate. Parents were primarily concerned with the experimental nature of the study, whereas physicians were concerned about accurate staging, with some overlap. We point out the necessity of assessing these concerns in predicting feasibility of and accrual to a therapy reduction study.

Background: Until now, only a few mouse-transplanted human tumors or experimental Wilms tumor (WT) cell lines have been described. The aim of this study was to show the biological behavior, including histology, immunohistochemistry (IHC), and molecular biology, of a WT including the original tumor and metastasis transferred into nude mice and followed for successive generations in xenografts., Methods: A WT metastasis was xenotransplanted into nude mice and the mice was monitored for 7 passages over a period of 29 months; the original neoplasm was comparatively studied. The morphology was evaluated by optical and electron microscopy. The protein expression was analyzed by immunohistochemistry in whole sections and in tissue microarray. The molecular studies were carried out by multiplex ligation-dependent probe amplification and polymerase chain reaction analysis., Results: The histology changed markedly between the fourth and fifth transfer. The tumor exhibited an increased epithelial component (>40%) together with a slowing in the growth rate (8 mo). An epithelial-mesenchymal transition seemed to take place in the fourth passage and increased thereafter. The genetic studies also showed a WT5 deletion and a MYCN gain in all the tumor samples in passage 4 and beyond, but did not show E-cadherin, β-catenin, and APC mutations., Conclusions: An epithelial pattern was associated with slow tumor growth, whereas the predominance of mesenchymal spindle cells with striated muscle cell differentiation was related with a high growth rate. The in vivo reorganization of the tumor components (blastemal, epithelial, and mesenchymal) does not seem to be related with the Wnt and EMT pathways.

Purpose of Review: To review the 2009/2010 literature on pediatric genitourinary tumors and highlight the most significant publications., Recent Findings: New techniques such as gene expression profiling, PET, nephron-sparing surgery, and stem cell transplantation are being incorporated into contemporary treatments for pediatric patients with genitourinary tumors. Biologic markers are increasingly being used to help with risk stratification of patients. WT1 mutation and 11p15 loss of heterozygosity have been associated with relapse in very low-risk Wilms tumors treated with surgery alone and may help reduce the use of chemotherapy in some children. Discussion continues on the use of fusion gene status to risk stratify alveolar rhabdomyosarcoma. Meta-analysis of the use of high-dose chemotherapy with autologous hematopoetic stem cell rescue in patients with relapsed Wilms tumor and rhabdomyosarcoma suggests that some patients may benefit more from conventional salvage chemotherapy. New agents are needed for patients with high-risk and relapsed disease to improve outcomes., Summary: In general, the prognosis for patients with pediatric genitourinary tumors is favorable. The elucidation of the molecular abnormalities in these tumors is determining risk stratification, treatment strategies, and candidates for new drug development.

Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries., Objective: The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types., Methods: This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations., Results: From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted., Conclusion: The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, malignant neoplasm usually present with the widespread abdominal serosal involvement and affects mainly adolescents and young adults. When presenting within visceral organs, as kidney, the diagnosis of DSRCT imposes significant difficulties. We present a case of primary DSRCT of the kidney in a 10-year-old boy mimicking clinically and pathologically Wilms tumor. The tumor showed morphologic and immunohistochemical features of DSRCT and the presence of the Ewing sarcoma and Wilm tumor 1 fusion transcripts resulting from the t(11;22) (p13;q12) reciprocal translocation. DSRCT should be considered in the differential diagnosis of Wilm tumor and other small blue-round cell tumors of the kidney.

Nestin is an intermediate filament that was first identified in neuroepithelial stem cells. During embryogenesis, nestin is expressed in a number of cell types, including neural crest cells and developing myocytes. We have recently shown that nestin is expressed in human podocytes and nephrogenic blastema. We sought to determine the utility of nestin expression in distinguishing pediatric tumors in the region of the kidney. Cases studied included Wilms tumor (n=24), nephroblastomatosis (n=6), renal cell carcinoma (n=19), renal clear cell sarcoma (n=9), mesoblastic nephroma (n=9), neuroblastoma (n=11), malignant rhabdoid tumor (n=8 including 2 renal), Ewing sarcoma (n=16 including 1 renal, 7 soft tissue, and 8 bone), intra-abdominal desmoplastic small round cell tumor (n=5), and rhabdomyosarcoma (n=8, all extrarenal). Nestin expression was assessed semiquantitatively by immunohistochemistry and then scored as positive or negative. All cases of Wilms tumor, mesoblastic nephroma, rhabdomyosarcoma, neuroblastoma, malignant rhabdoid tumor, and desmoplastic small round cell tumor were nestin-positive. In Wilms tumor and nephroblastomatosis, nestin was expressed in blastema and glomeruloid structures, but not tubules. In neuroblastoma, positive staining was detected regardless of degree of differentiation. The majority of Ewing sarcoma and renal cell carcinoma were negative. Expression in clear cell sarcoma was variable with 5 cases negative and 4 cases positive. Thus, nestin is a highly sensitive, but nonspecific, marker of Wilms tumor in the context of tumors that may occur in or around the kidney. Nestin reactivity may be useful in differentiating Wilms tumor from Ewing sarcoma, renal cell carcinoma, or nestin-negative clear cell sarcoma.

Serum levels of midkine (MK), a heparin-binding growth factor, are elevated in adult cancer patients. We analyzed sera of pediatric tumor patients in comparison to a large number of children and adolescents without malignant disease. MK was studied in sera of 152 noncancer patients and 29 embryonal tumor patients (14 nephroblastoma, 10 neuroblastoma, and 5 rhabdomyosarcoma) using an enzyme-linked immunosorbent assay. Noncancer patients underwent elective surgical procedures or suffered from an endocrinologic disease. They had no evidence of inflammation or injury. MK serum levels were significantly higher in tumor patients (median 0.621 ng/mL) than in noncancer patients. About 86% of tumor patients were identified using a cut-off value of 0.176 ng/mL. MK values did neither correlate with tumor size nor with stage or histology, but decreased in half of the nephroblastoma patients after chemotherapy and surgery. MK values were found to be elevated in only 2 out of 5 rhabdomyosarcoma patients. MK may serve as an additional marker for the detection of pediatric embryonal tumors, but its clinical relevance for the evaluation of response to therapy needs further study.

Purpose of Review: We will review the 2007/2008 literature on pediatric genitourinary tumors., Recent Findings: Newly identified constitutional epigenetic defects in Wilms tumor genes extend the understanding of Wilms tumor risk in children lacking syndromic features, and add to the complexity of the pathogenesis of these tumor suppressor genes. Pediatric renal cell carcinoma has distinct molecular characteristics and clinical associations from the adult counterpart. The pathway from PAX3-FKHR translocation to the development of rhabdomyosarcoma tumors has been further elucidated., Summary: Therapeutic strategies continue to be driven by developments in molecular diagnostics in pediatric genitourinary tumors.

Purpose of Review: We will review the recent (2006/2007) literature on pediatric genitourinary tumors., Recent Findings: The WTX gene is now the most common known gene mutation in Wilms' tumor. It acts as a tumor suppressor gene and may play a role in other malignancies. Current clinical trials have incorporated the loss of heterozygosity of 1p and 16q along with age, tumor size, stage, and response to therapy to risk stratify therapy. The PAX3-FOX01 gene fusion and the IGF-1R-signaling and mTOR-signaling pathways are implicated in rhabdomyosarcoma biology, and hence are promising therapeutic targets for this tumor., Summary: Progress is being made in understanding the pathogenesis of genitourinary tumors in children, and the prognosis for these children continues to improve. Current treatment strategies are focused on improving event-free survival while decreasing late effects from therapy.

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Aim: Wilms tumor (WT) usually shows a bi-phasic or tri-phasic morphology comprised of blastemal, stromal, and epithelial cells. Other biphasic renal tumors that can mimic WT may pose diagnostic dilemmas especially in preoperative needle biopsy samples. This tissue microarray study was designed to investigate the immunohistochemical features that may prove useful in the accurate diagnosis of WT in small biopsy samples., Methods: Eight punches from each paraffin block of 45 cases of WTs were used to construct 5 tissue microarray blocks. Immunohistochemical reactions of blastemal, stromal, and epithelial cells of each core to a panel of 37 antibodies were evaluated., Results: Blastemal elements expressed CD56 (22, 57%), CD57 (19, 55%), cytokeratin 22 (CK22) (12, 27%), and CK8 (9, 21%). Epithelial cells were stained mostly with CK22 (17, 94%), CK18 (12, 66%), CK8 (14, 70%), CD57 (10, 76%), CD56 (6, 43%), EMA (7, 44%), and CK19 (5, 25%). Stromal cells expressed SMA (21, 50%), actin (18, 48%), desmin (9, 20%), CD34 (7, 24%), CD57 (5, 18%), and CD56 (5, 15%). Only one case was positive for CK5/6, CK13, CK14, and CK20. Calretinin expression was seen in the stromal cells of 3 and placental alkaline phosphatase expression was observed in 1 case. All 3 components were negative for CK1, CK7, myoglobin, Myf-4, MyoD1, HMB45, chromogranin A, synaptophysin, Melan A, beta-HCG, alpha-HCG, alpha-Inhibin, renal cell carcinoma antigen, glycophorin A, PSA, and estrogen and progesterone receptors., Conclusions: CD56, CD57, CK22, CK18, CK8, EMA, SMA, and actin are useful markers for an accurate diagnosis of WT in small biopsy samples.

Adrenal hemorrhage after the neonatal period is rare. It most often occurs with coagulation disorders or child abuse. Spontaneous bleeding within an adrenal neuroblastoma has been described, but acute massive hemorrhage is exceptional. We describe a case of neuroblastoma of the adrenal gland presenting with acute life-threatening abdominal hemorrhage.

We present a 7-month-old male infant with stage I Wilms tumor who unexpectedly died from a catastrophic intracerebral hemorrhage, 4 months after completion of chemotherapy and complete surgical resection of the tumor. The precise etiology underlying the fatal event remains unclear as postmortem was refused, but we postulate spontaneous hemorrhage from an underlying cerebral vascular malformation as the most likely cause, which led to the child's unfortunate demise. Although extremely rare, cerebral vascular anomalies have previously been reported in children with Wilms tumor. The coexistence of the 2 uncommon disorders may be related to their congenital origin. Wilms tumor diagnosed in very young infants have clinical and morphologic attributes that do not pertain in older children and the risk of associated congenital anomalies is also much higher among those discovered in the first year of life. This raises the question whether routine magnetic resonance imaging should not be performed in infants less than a year with Wilms tumor, as part of the initial evaluation, to exclude cerebral metastases and underlying vascular malformations.

Purpose of Review: We will review the 2005 and 2006 literature on pediatric genitourinary tumors., Recent Findings: Survival continues to improve for primary renal, bladder/prostate and testicular tumors in childhood. The addition of more intensive chemotherapy for anaplastic histology disease, recognition of loss of heterozygosity for chromosomes 1p and 16q as an adverse prognostic factor in favorable histology Wilms' tumor, and the utilization of molecular markers to better characterize all renal tumors will better enable individualized therapy. Recognition and treatment of anaplastic histology and bilateral Wilms' tumor remains a challenge. In rhabdomyosarcoma, genitourinary site and embryonal histology confer a relatively favorable prognosis., Summary: Advances in molecular oncology, diagnostic imaging, surgical approaches and long-term follow-up of childhood cancer survivors drive risk-stratified therapy in pediatric genitourinary tumors.

Unlabelled: The clinical features and management of severe hypertension (HT) (blood pressure > 99th percentile + 5 mm Hg) have been rarely described in pediatric oncology., Objectives: Retrospective descriptive study of the case files of 31 patients followed in the Institut Curie Department of Pediatric Oncology between 1999 and 2004 and presenting severe HT at the time of diagnosis of their tumor., Results: The median age was 2 years 1 month (range: 3 mo to 6 y 8 mo). Median blood pressure was 99th percentile + 30 mm Hg (range: 99th percentile + 7 mm Hg to 99th percentile + 62 mm Hg). The tumors presented by these children were: Wilms tumor (n=17, ie, 20% of all Wilms tumors treated during this period), neuroblastoma (n=12, ie, 10% of all neuroblastomas treated during this period) or other tumors (n=2). HT was asymptomatic in all children. Initial management consisted of etiologic treatment by primary chemotherapy and/or surgical resection of the tumor, associated with antihypertensive therapy, initially administered by intravenous injection for 12 children (nicardipine, labetalol) and then orally in all children (calcium channel blockers, n=23; angiotensin-converting enzyme inhibitor, n=16; beta-blockers, n=4; alpha/beta-blockers, n=2; diuretics, n=1). Dual therapy was necessary in 7 cases and triple therapy was necessary in 1 case. The median duration of antihypertensive therapy was 40 days (range: 9 to 195). No child developed a serious complication of HT., Conclusions: Initial HT is a frequent complication of Wilms tumor and neuroblastoma and affects young children (< 2.5 y). It is often severe, asymptomatic, but needs specific treatment and resolves after treatment of the tumor.

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.

A27-year-old woman presented with back and abdominal pain. She was diagnosed in infancy with Beckwith-Wiedemann syndrome and bilateral multifocal perilobar nephrogenic rests that progressed to diffuse nephroblastomatosis with neoplastic nephroblastomatous rests at 14 months of age and subsequently to a right Wilms tumor at 5 years of age. Computed tomography of the abdomen during the current admission showed multiple obstructed calices. Ureteroscopic inspection of the left kidney revealed severe intrarenal scarring with multiple infundibular stenosis, hydrocalices, and nephrocalcinosis. Renal biopsy showed sclerotic glomeruli with calcification and scarring and persistent subcapsular nodular renal blastema. Electrocautery incision and balloon dilatation provided temporary pain relief. After discharge, the patient has had two or three episodes of recurrent pain associated with new areas of infundibular stenoses and renal cysts. Bilateral nephrectomy and renal transplantation is being considered for management of progressive disease and relief of intractable pain. The potential causes of progressive and severe intrarenal fibrosis, infundibular stenosis and nephrocalcinosis, and renal cysts in this patient may include abnormal renal development secondary to Beckwith-Wiedemann syndrome itself, radiation or chemotherapy damage, or a combination.

Each year advances are made in the clinical evaluation and treatment of genitourinary tumors in children. Understanding of cellular, molecular, and genetic processes in tumorigenesis is evolving rapidly. In addition, information is accumulating about the long-term outcome and complications associated with treatment modalities. This article reviews the 2001 literature on pediatric Wilms tumor, other renal tumors, rhabdomyosarcoma of the pelvis, paratesticular rhabdomyosarcoma, and testicular tumors. The emphasis in molecular biology is to identify molecular or genetic markers that predict outcome. The National Wilms' Tumor Study Group reported on the complications of surgery and the decreased complication rate when these procedures are performed by pediatric surgical specialists. Long-term complications of treatment are also discussed, including short stature and leukemia. The Intergroup Rhabdomyosarcoma Study Group reported on the results of treatment for nonmetastatic disease and the goals of the upcoming Study V, reduction of chemotherapy and radiotherapy. They also presented data from Study IV and discussed the findings on improved prognosis.

Involvement of the inferior vena cava with tumor thrombus has been reported in 5 to 10% of patients with Wilms' tumor. Preoperative imaging usually alerts the surgeon to the extent of the intravascular extension. We present a case report of trauma to a previously undiagnosed Wilms' tumor that resulted in a fatal intraoperative pulmonary tumor embolus.

Objective: To analyze retrospectively results of reverse transcription polymerase chain reaction (RT-PCR) testing and demographic information in patients with known or suspected Ewing sarcoma/primitive neuroectodermal tumor family of tumors referred to the National Cancer Institute and to describe factors influencing the determination of molecular marker status., Patients and Methods: Tumor samples from 76 patients from February 1997 to December 1999 were analyzed. In all cases, the diagnosis of this family of tumors was confirmed by histopathologic review., Results: In 58 patients, the presence of a translocation associated with this family of tumors was confirmed using RT-PCR. Specifically, there were 45 Ewing sarcoma (EWS)-FLI type 1 translocations, four EWS-FLI type 2 translocations, five EWS-ERG translocations, and four less common EWS-FLI variants. Of patients with a confirmed translocation, four were confirmed only after nested RT-PCR techniques were used. In five patients who initially underwent needle biopsy, the diagnosis was confirmed only after open biopsy or repeat needle biopsy was undertaken. Samples from 18 patients were translocation-negative. Of these, seven samples were deemed inadequate for RT-PCR testing as a result of inappropriate tissue handling or the presence of necrotic material. Five patients were found to have a different diagnosis after complete histopathologic and molecular characterization. Six samples remained, in which adequate tissue was obtained with no evidence of a characteristic translocation., Conclusions: In apparently translocation-negative samples, close attention should be given to the possibility of an alternative diagnosis, the potential need for nested RT-PCR, and the possibility of an inadequate sample. Strong consideration should be given to the use of open biopsy as opposed to needle biopsy to avoid the need for repeat biopsies and the potential for inaccurate assessment of molecular marker status.

Purpose: We designed this study to differentiate the clinical presentation, particularly the incidence of hematuria, of a rhabdoid tumor of the kidney (RTK), a rare but highly malignant tumor, from a Wilms tumor., Patients and Methods: We reviewed patient flow charts from the National Wilms Tumor Study Group and queried participating hospitals to obtain additional information regarding presenting symptoms and laboratory data for fifty patients. Patient ages ranged from 2 days to 3.5 years with a mean of 11 months. We documented the presence of gross and microscopic hematuria, fever, and hypercalcemia., Results: Whereas 75% of children with rhabdoid tumor of the kidney (RTK) had stage III (44%), IV (27%), or V (4%) tumors, 67% of children with Wilms tumors had stage I (41%) or II (26%) tumors. Either gross or microscopic hematuria was present in 84.4% (27/32) of the patients with RTK. Gross hematuria was present in 59% (22/37) of children with RTK compared with 18% previously reported with Wilms tumor. Microscopic hematuria was present in 76% (22/29) of children with RTK compared with 24% previously reported with Wilms tumor. Fever was found in 44% (16/36) of children with RTK, compared with 22% of children previously reported with Wilms tumor. Hypercalcemia was seen 26% (6/23) of children with RTK., Conclusion: Although diagnosis of any renal mass still must be confirmed with histopathologic features, a distinct clinical presentation with fever, hematuria, a young age, and high-tumor stage at presentation suggests the diagnosis of RTK.

This report describes an unusual case of uterine cervical Wilms tumor treated successfully without hysterectomy or radiation therapy. The 12-year-old white girl developed a persistent vaginal discharge. Her pelvic examination revealed a large mass involving the entire upper vagina, obscuring the cervix. Biopsy of the mass was consistent with Wilms tumor with favorable histology. The tumor was not initially resected because the resection would involve hysterectomy and partial resection of the bladder wall. The patient was treated with preexcisional chemotherapy consisted of alternating vincristine, doxorubicin, cyclophosphamide and carboplatin/etoposide. Repeat magnetic resonance imaging after 5 weeks of chemotherapy demonstrated marked reduction of the tumor size. The tumor was easily removed by transsection of the stalk followed by cold-knife conization of the cervix. The patient received four more cycles of chemotherapy and remained in complete remission 12 months after completion of chemotherapy. This report suggests that in selected cases, chemotherapy can reduce tumor size sufficiently in patients with bulky cervical Wilms tumor to allow local resection and avoid hysterectomy.

Advances in our knowledge of pediatric genitourinary tumors are being made at a rapid pace at both the basic science and clinical levels. As the molecular mechanisms underlying these malignancies are being uncovered, treatment options are being modified to decrease morbidity and, ultimately, increase survival. This article reviews the recent literature on Wilms' tumor, rhabdomyosarcoma, and testicular tumors.

Each year advances are made in the clinical evaluation and treatment of genitourinary tumors in children. Our understanding of cellular, molecular, and genetic processes in tumorigenesis is evolving rapidly. In addition, knowledge concerning long-term outcome and complications associated with current treatments is increasing. In this article, we review recent literature on pediatric rhabdomyosarcoma, Wilms' tumor, and testicular tumors.

Although genitourinary tumors make up only 10% of childhood cancers, with Wilms' tumor accounting for most, the study of these tumors has yielded a model of cancer development. Tremendous interinstitutional and international cooperation has improved the survival and lowered the morbidity of treatment. Advances in molecular biology and improvement in experimental techniques make this a tremendously exciting field, with discoveries being made almost routinely. Most importantly, however, the study of this group of tumors and the ensuing application of multi-modality therapy has saved the lives of thousands of children.

We report on the clinical and pathologic findings in 31 cases of adenosarcoma of the uterus subjected to hysterectomy and staging laparotomy. Nine of 30 patients (30%) have had recurrent tumor and six of 30 (20%) have already died of tumor in a relatively short follow-up period (mean, 38.3 months). Seventeen of 31 cases were diagnosed as adenosarcoma with sarcomatous overgrowth (SO). Ten of these 17 with SO contained focal or extensive rhabdomyosarcoma. In six cases, extrauterine spread was identified as follows (two patients had two sites each): vaginal involvement (two cases), pelvic lymph node metastases (two), positive peritoneal cytologic findings (two), parametrial invasion (one), and ovarian metastasis (one). Extrauterine spread (stage III) (p less than 0.001) and myometrial invasion (p = 0.04) were associated with higher rates of recurrence. The presence of lymphatic and/or vascular invasion, SO, and rhabdomyosarcomatous differentiation also indicated poor prognosis but did not attain statistical significance. Based on this experience, staging laparotomy including peritoneal cytology is suggested in cases of clinical stages I and II adenosarcoma. The differential diagnosis of these tumors is also discussed.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity was investigated in 10 cases of angiomyolipoma (AML) (1 with massive regional lymph node involvement) of the kidney and detected in all of them. No HMB-45 immunoreactivity was found in other tumors of the region which can occasionally be confused with AML, such as renal cell carcinoma, Wilms' tumor, and retroperitoneal sarcoma (leiomyosarcoma and liposarcoma). These findings indicate that HMB-45 is not a melanocyte-restricted marker and suggest that its expression might be useful in distinguishing AML from other tumors of the kidney and retroperitoneum.

Drash syndrome is a disorder of the genitourinary ridge differentiation and includes abnormal genital development, nephropathy, and a predisposition to develop Wilms tumor. In three patients with Drash syndrome, magnetic resonance was correlated with ultrasound, CT, and surgical findings. Two patients with glomerulonephritis had enlarged kidneys, loss of corticomedullary differentiation, and overall decrease in signal intensity on T1-weighted sequences. Two large Wilms tumors were identified, but a small 1 cm nephroblastoma was not recognized. Anomalies associated with ambiguous genitalia, such as absent uterus, were also correctly diagnosed.