Renal Tumors In Children Research Articles

Immunohistochemical expression of p53 oncoprotein in Wilms tumour in relation to histological components, histological types and preoperative chemotherapy

There have been only few studies of immunoexpression of p53 in Wilms tumour (WT), and their results are somewhat contradictory. The aim of the study was to determine p53 immunohistochemical expression in WT in relation to its histological components, histological prognostic types classified according to the SIOP Working Classification of Renal Tumours of Childhood (2001), and influence of preoperative chemotherapy. The analyses are based on 79 primary WTs treated in single institution according to SIOP protocols between 1983-2001. For the immunohistochemical detection of p53, the monoclonal p53 antibody (DO-7, DAKO) was used. Semiquantitative grading of nuclear staining was done. The immunoexpression of p53 was significantly higher in the blastemal and epithelial than in the stromal component (p < 0.001). It was significantly correlated to WT histological prognostic types (p = 0.039).The exensivity of p53 immunoexpression was higher in anaplastic components but a difference between WT type of diffuse anaplasia and all other types was nonsignificant (p = 0.10). Five blastemal type WTs were p53 immunopositive and four immunonegative. There was no difference in p53 immunopositivity between WT treated with the preoperative chemotherapy and primary resected WT (p = 0.88). The immunoexpression of p53 in WT was significantly higher in the blastemal and epithelial than in the stromal component. It was in significant correlation with histological types of WT. The anaplastic component had noticeable but statistically not significantly higher p53 immunoexpression than non-anaplastic. The preoperative chemotherapy did not modify p53 immunoexpression of WT which had been found in other similar studies.

Wilms tumour: prognostic factors, staging, therapy and late effects

Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Société Internationale d'Oncologie Pédiatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial development and participation will improve matching of treatment needs with prognosis, reducing long-term complications in the majority. The advent of molecular markers of disease severity and improved functional imaging might help.

1108 POSTER Health-related quality of life (HRQOL) and kidney cancer-related symptoms in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib versus interferon (IFN)-alfa: results for European and US subsample analyses in a randomized, multinational phase III trial

Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease.

Part II: Treatment of primary malignant non-Wilms' renal tumours in children

Renal-cell carcinoma, clear-cell sarcoma, (congenital) mesoblastic nephroma, rhabdoid tumour, and renal medullary carcinoma form a heterogeneous group of childhood renal malignancies known as non-Wilms' tumours. Progress has been slow in improving the management of these tumours to decrease morbidity and increase survival. However, greater cooperation between national and international centres should engender specialisation, and an increased knowledge of the molecular biology of these tumours will inevitably lead to substantial progress over the next decade. This review is the second of two parts: the first part provided an updated review of the clinical presentation, imaging, and pathology of non-Wilms' tumours and this second part provides an updated review of the treatment of these tumours.

Clear cell sarcoma, cellular mesoblastic nephroma and metanephric adenoma: cytological features and differential diagnosis with Wilms tumour

Wilms' Tumour (WT) is the most common kidney tumour in childhood, this fact and the embryonic complexity of WT create, whenever one of its three classical components predominates in cytologic smears, difficulties in the differential diagnoses with other less common entities. In the present study, we review the cytological and immunohistochemical characteristics of three children renal tumours, a Clear Cell Sarcoma of the Kidney (CCSK-case1), a Cellular Mesoblastic Nephroma (CMN-case2) and a Metanephric Adenoma (MA-case3) and compare them, for differential diagnostic purposes, with smears of blastematous, mesenchymal and epithelial predominant WTs, previously diagnosed in our Department. In all cases a mass was detected in the abdomen (2 and 8 year old children-cases 1 and 3, respectively), and pre-birth in case 2 (the tumour was detected during pregnancy). Fine needle biopsy was performed followed by routine cytologic examination. The presence of moderate amount of blue pale cytoplasm in neoplastic cells (case1), the presence of tightly cohesive, bland, spindle tumour cells (case2) and the identification of small, well differentiated epithelial tubules with psammoma bodies in case 3, were the main morphologic characteristics that we think represent the most important elements for distinguishing our cases from a WT. Immunoreactivity was only helpful in case 1 as we found a characteristic dot-like pattern positivity for vimentin, in the absence of immunoreactivity for the other markers that are usually positive in WT. Summing up, these three cases demonstrate that cytopathologists should be aware of the occurrence of uncommon renal neoplasms in childhood and should be acquainted with their characteristics, in order to avoid false diagnoses.

Part I: Primary malignant non-Wilms' renal tumours in children

Non-Wilms' tumours form a small heterogeneous group of clinically significant renal malignancies in children, including renal-cell carcinoma, clear-cell sarcoma, (congenital) mesoblastic nephroma, rhabdoid tumour, and renal medullary carcinoma. Good progress has been made in the assessment of these tumours, which has led to a greater understanding of the molecular changes that occur in their development. This review is the first of two parts, and provides an updated review of the clinical presentation, imaging, and pathology of these tumours.

Wilms-Tumor bei Erwachsenen

Wilms' tumor (nephroblastoma) is the most frequent renal tumor in childhood. In contrast nephroblastoma in adults is rare, and the disease used to have a poor prognosis. Of 1,300 registered patients, a total of 41 patients older than 16 years were enrolled in the pediatric nephroblastoma trial from 1994 to 2005. Median age at diagnosis was 25.4 years (range: 16-62 years). Treatment was given according to the pediatric protocol. The adults had higher local stages, more frequent metastasis, and developed more toxicity due to therapy. Vincristine caused severe neurotoxicity in many cases. The distribution of histological subtypes was similar to the children's. The outcome is better than previously described with an overall survival of 71%. Patients with local stage I and II have an event-free survival of 84%. This is comparable to children's survival rates. Adults with nephroblastoma have a very good prognosis if treated according to a pediatric protocol.

Three years experience of infantile Wilms tumour at a single institute in a developing country

20028 Background: Wilms tumor (nephroblastoma) is the second most common malignant retroperitoneal tumor. It is the most common primary renal tumour of childhood and is a paradigm for multimodal treatment of a pediatric malignant solid tumor. The median age at diagnosis is 4 years and it is uncommon in infancy. We present a three year retrospective analysis of Wilms tumor in infants treated at out institute. Methods: A total of 16 cases of Wilms tumor were diagnosed in pediatric patients aged one and below between January 2003 to December 2005. Out of these, 11 patients were evaluable. All of them were given treatment as per the National Wilms Tumor Study- 5 protocol. Results: The median age of presentation was 10.8 months, one child was 5 months old rest all were between 10 and 12 months. The male to female ratio was 2.3:1. The most common presenting complaint was mass per abdomen, which was seen in 10 patients, one patient presented with pain in abdomen and hematuria. None of the patients had evidence of any other systemic involvement. 7 patients were in Stage I, 2 each were in stage II and stage III. Triphasic classical type (favorable) was the histopathological subtype in 9 patients and 2 had unfavorable histopathological subtypes. All the 10 cases underwent total Nephrectomy [three at our institute and the rest elsewhere] of the diseased kidney followed by treatment as per the National Wilms Tumor Study- 5 protocol with 50% dose reduction. 7 cases (70%) showed complete remission and presently are under observation. Three cases were lost to follow up after surgery. One patient with stage three disease was given anterior chemotherapy but was lost to follow up after 9 weeks of chemotherapy. Conclusion: Wilms tumor presenting in infancy when treated appropriately has a good outcome although not as good as in older children. No significant financial relationships to disclose.

Drug Resistance in Renal Tumors of Childhood

Renal cancers are as one of the most common drug resistant neoplasms affecting children and multidrug resistance (MDR) happened to be an important reason for the failure of chemotherapy in refractory cancers of childhood. MDR can be intrinsic or acquired, depending on the time of its occurrence, either at diagnosis or during chemotherapy. Renal cancers often have intrinsic form of MDR because of de novo expression of P-glycoprotein (P-gp) in renal cells. Molecular investigations on MDR during the past two decades have led to the isolation and characterization of genes coding for P-gp, multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), breast cancer resistance protein (BCRP/MXR), drug resistance-associated protein (DRP), and ATP-binding cassette protein (ABCP). Several molecular probes, primer pairs, and monoclonal antibodies have been developed over the years to quantify the regulation and expression of these drug resistance markers in tumor cells. Methodologies have also been standardized to estimate the gene amplification, mRNA and protein expression, and functionality of drug resistance proteins in clinical specimens from cancer patients. Because of the recent developments in microarray technology, DNA and protein arrays against drug resistant genes are available commercially now. This review includes techniques for detection and quantification of the expression and function of these drug resistance genes in childhood renal tumors. Since these markers have clinical significance, currently available technology warrants the application of these markers in clinical oncology. Moreover, the first, second and third generation drug resistance modifiers have been developed over the past several years for overcoming drug resistance problem in tumor cells. Unfortunately, these reversing agents are yet to be proved successful clinically. Since treatment protocols are usually adopted from adult tumor patients into childhood population, clinical trials with modifying agents are yet to be undertaken and/or concluded in pediatric renal cancer patients. More clinical studies may be required to analyze the genes involved in the MDR of childhood renal cancer patients and trials have to be undertaken to evaluate the efficacy of MDR modifying agents in them, at least in parallel with adult patients.

919: Ureteral Extension in Childhood Renal Tumors: A Report From the National Wilms Tumor Study Group (NWTSG)

919: Ureteral Extension in Childhood Renal Tumors: A Report From the National Wilms Tumor Study Group (NWTSG)

Ureteral extension in childhood renal tumors: a report from the national wilms tumor study group (NWTSG)

Purpose To define the clinical presentation, associated pathologic features and clinical outcome of these patients (pts). Material and methods Pts with ureteral extension enrolled in NWTS-3, -4, and -5 were reviewed. Presenting symptoms, imaging, pathology, surgery and outcome were recorded. Results 45 children were identified. Clinical presentation included gross hematuria in 22 pts, 2 had passage of tissue per urethra and one child had a urethral mass. Ureteral extension was identified on preoperative imaging in 14 pts, intraoperatively in 22, and on pathologic exam in 9. Hydronephrosis was noted in 12 pts and there was non function of the kidney in 7 pts. Cystoscopy was performed in 12 pts. Findings included tumor seen at the ureteral orifice in 6 pts and bleeding from the orifice in one. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 pts, including 2 of 7 pts with separate removal of the ureteral extension. The tumor extended into the proximal ureter in 23 pts, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. Favorable histology WT was found in 38 pts, 4 had anaplasia, 2 had rhadoid tumor and 1 clear cell sarcoma. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. 3 deaths were in pts with unfavorable histology. Conclusions Ureteral extension occurs in approximately 2% of pts with WT. The diagnosis should be suspected in pts in with gross hematuria or a nonfunctioning kidney. Preoperative diagnosis is important since complete resection of the involved portion of ureter can avoid residual disease and the need for radiation.

Risikofaktoren intra- und postoperativer Komplikationen in der Chirurgie des Wilms-Tumors

Wilms' tumor is the most common renal tumor in childhood. Preoperative treatment is still under discussion. The aim of this study was to determine, using our own patient collective, the risk factors for and type of intraoperative complications which can occur. In addition, the influence of the surgical procedure and tumor size on the complications and survival rate was analyzed. A total of 66 patients with Wilms' tumor were retrospectively analyzed. Evaluation included histology, size of the primary tumor as well as neoadjuvant and adjuvant chemotherapy. The total survival rate over periods of 5 and 10 years postoperatively were analysed using Kaplan-Meier survival probabilities. All patients underwent radical nephrectomy: 63 using the transperitoneal and three the lumbar approach. The tumors had a mean size of 9.8 cm (range 2.5-20.0). Twenty patients (30.3%) received neoadjuvant chemotherapy for tumor reduction, while 46 patients underwent surgery without preoperative chemotherapy. Complications occurred in eight patients (15.2%). In two, a the tumor ruptured under surgery, four patients developed an ileus and two suffered cardiac arrest. One patient had postoperative hypertonia and another an incisional hernia. All complications occurred with a tumor size >5 cm or in the patient group without neoadjuvant chemotherapy. The 10 year survival rate was 89.4%. The risk of complications is associated with the local size of the primary tumor. Through tumor reduction, neoadjuvant chemotherapy influences the expression of the such complications. Transperitoneal tumor nephrectomy is the method of choice in surgery for Wilms' tumors.

Renal cell carcinoma in children under 10 years old: a presentation of four cases

Renal cell carcinoma (RCC) in childhood is a unique disease entity, representing only 2.3-6.6% of all renal tumors in children. Most experience with pediatric RCC is limited to case reports or case series consisting of relatively small numbers of cases. The aim of this study is to present four additional cases of this unique disease entity. The records of four patients presenting to our institution with renal cell carcinoma between 1986 and 2006 were examined. Only patients younger than 10 years were included. The clinical data included age, sex, signs and symptoms, surgery performed and clinical outcome. Data recorded from the pathology reports included tumor size, histologic subtype, grade (WHO), and stage (TNM). There were three boys and one girl aged between 11 months and 10 years at presentation. The classic triad of flank pain, gross hematuria and palpable abdominal mass were not encountered. A histopathological diagnosis of RCC was confirmed in all four cases without any positive lymph node involvement. Due to the increased detection of tumors with the use of imaging techniques such as ultrasound and computerized tomography, an increased number of incidentally diagnosed RCCs are found. The primary choice of the treatment of any stage of RCC is surgical excision. However, the preoperative diagnosis of tumor in children is difficult and the effects of chemotherapy, including immunotherapy, are unclear.

Wilms’ tumour in adults: a case report and review of the literature

Wilms' tumour is a very rare adult malignancy representing 1% of adult renal tumours. It is however the most common renal tumour of childhood, and adult patients are treated in accordance with paediatric protocols. To review modern day management of adult Wilms' tumour. We report a case of adult Wilms' tumour and discuss the management including the use of newer treatment modalities. Following diagnostic nephrectomy, our patient was treated with chemotherapy in accordance with North American paediatric protocols and PET scanning was used to diagnose early relapse. In the absence of randomised controlled data, central reporting of cases of adult Wilms' Tumour may help improve management. The incorporation of newer chemotherapeutic agents, high-dose therapy and PET scanning into treatment protocols should improve outcome for these patients.

Wilms-Tumor – Update 2007

Due to the close interdisciplinary work of surgeons, radiologists and oncologists, the prognosis for Wilms' tumor (the most common renal tumor in childhood) has been dramatically improved over the last few decades. The treatment of such tumors is currently carried out worldwide by two study groups, in North America the National Wilms' Tumor Study (NWTS) and in Europe the Society of Paediatric Oncology (SIOP). Here we present an overview of the current treatment results and discuss future diagnostic and therapeutic strategies.

Treatment of Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma—A Report From the SIOP/GPOH Study Group

Cystic partially differentiated nephroblastoma is a rare variant of Wilms tumor, and might be confused with cystic nephroma. Definitive diagnosis can only be made by histological examination. Therefore, initiation of therapy, either primary nephrectomy or preoperative chemotherapy, might create a dilemma when radiological diagnosis is doubtful. To define treatment strategies for these entities, we reviewed the records of 1,245 patients enrolled in SIOP (International Society of Pediatric Oncology) trials 93-01 and 2001 GPOH (German Society of Pediatric Oncology and Hematology) between July 1993 and August 2004. Data were collected retrospectively. Therapy, outcome and preoperative management were evaluated. To confirm diagnosis of cystic nephroma/partially differentiated nephroblastoma, all patients underwent review by the Reference Pathology Center of SIOP/GPOH. A total of 14 patients with diagnoses of cystic nephroma (7) and cystic partially differentiated nephroblastoma (7) were identified. Median patient age at diagnosis was 1 year (0.46 to 3). Two patients received preoperative chemotherapy. Primary nephrectomy was performed in 12 patients. Two patients underwent partial nephrectomy. In 1 child postoperative chemotherapy was administered. None of the patients had progression of disease or recurrence. Overall survival was 100%. Median followup was 2.41 years (0.3 to 9). In cystic renal tumors radiological findings should always be reviewed by the reference radiologist of the treatment protocol study group. Irrespective of the chosen therapy, outcome of cystic nephroma and cystic partially differentiated nephroblastoma is favorable. Even in large international trials the number of patients with cystic nephroma or cystic partially differentiated nephroblastoma is too small for statistical analysis.

Adult Wilms' tumour: a case report with review of literature

BackgroundWilms' tumor is the commonest primary malignant renal tumor in childhood. Rarely, it may present in the adult age group.Case presentationWe report a 48-year-old male presenting with flank pain and haematuria. Abdominal ultrasound revealed a right renal mass measuring 11 × 10 cms, and a clinical diagnosis of renal cell carcinoma was made. Nephrectomy was performed, and a final diagnosis of adult Wilms' tumor was made based on the criteria proposed by Kilton et al.ConclusionThe possibility of an adult Wilms' tumor should be considered when a patient presents with pain in the flank and a renal mass. Rarity of the tumor favors documentation in literature.

Metanephric adenoma: A rare differential diagnosis of renal tumor in children

Metanephric adenoma is an extremely rare tumor of the kidney. The clinical and anatomic characteristics are not yet well defined, but it is currently considered to be a benign tumor with a good prognosis, although recently two metastatic cases have been reported. Around 50% of cases are incidental findings, and symptoms include polycythemia, abdominal pain, hematuria and palpable mass. The morphological characteristics are similar to those of Wilms' tumor, suggesting a common embryological precursor. We present here the youngest girl yet to be reported with a diagnosis of metanephric adenoma.

PRCC-TFE3 Renal cell carcinoma in a boy with a history of contralateral mesoblastic nephroma

The genetics of renal tumors in children is widely recognized. However, most of the studies published to date emphasize the association between Wilms tumor and the WT-1 gene. Recently, a unique translocation between the X chromosome and chromosome 1 or t(X;1) has been described in several reports of renal cell carcinomas (RCCs) diagnosed in children and adolescents that results in PRCC-TFE3 gene fusion. We report here a 9-year old African-American boy with a history of a right congenital mesoblastic nephroma treated with nephrectomy and followed by annual checkups. After 9 years, he was diagnosed with a mass at the hilum of the left kidney during the work-up of new-onset hypertension. A limited biopsy revealed densely hyalinized connective tissue that was initially interpreted to be a hyalinized contralateral mesoblastic nephroma. The child received chemotherapy, but the mass continued to grow. He underwent a left nephrectomy, and the pathology was diagnostic for a clear cell RCC. Chromosomal analysis disclosed a t(X;1)(p11.2;q21) translocation, which is known to result in a PRCC-TFE3 gene fusion. The tumor showed nuclear labeling for TFE3 protein by immunohistochemistry, supporting the above diagnosis. He has been on hemodialysis, is tumor free, and has not been receiving chemotherapy for 24 months. This is the first report of a RCC as a second malignant neoplasm in a child treated for a congenital mesoblastic nephroma.

Malignant renal tumours incidence and survival in European children (1978–1997): Report from the Automated Childhood Cancer Information System project

More than 5000 cases of malignant renal tumour diagnosed in children under the age of 15 years during the period 1978–1997 in Europe, were extracted from the database of the Automated Childhood Cancer Information System (ACCIS). In 1988–1997 the age-standardised incidence rate of childhood renal tumours in Europe was 8.8 per million, with significant differences between regions. Wilms’ tumour (WT, M-8960) accounted for 93% of renal tumours and about 7% were bilateral. The incidence rates of WT increased over the 20 years, by 0.7% per year. European 5-year survival for children diagnosed with WT in 1988–1997 was 85%, ranging from 73% in the East to 91% in the North. Patients in the age group 0–3 years at diagnosis had a more favourable prognosis (5-year survival 87%) than those diagnosed later (81%), P < 0.0001. Patients with unilateral WT ( n = 2085) had better 5-year survival (85%) than 154 patients with bilateral tumours (76%), P = 0.003. Five-year survival for 64 patients with clear cell sarcoma of kidney was 68%, for 43 patients with rhabdoid tumour of kidney it was 23%, and for 56 patients with renal cell carcinoma it was 87%. For combined European data, 5-year survival for WT increased from 73% in 1978–1982 to 87% in 1993–1997 and the increase was significant in three out of five regions (East, North and West). Further development and exploitation of the ACCIS database will benefit clinical management and aetiological studies.