Late relapsing Wilms tumor with rhabdomyomatous differentiation

The authors report a patient with abdominally relapsed Wilms tumor with rhabdomyomatous differentiation leading to renal failure and death 9 years after the initial diagnosis. The patient was treated with intensive chemotherapy because of inoperable tumor but no response was obtained. The prognosis of children with Wilms tumor relapsed in abdomen and in previously irradiated fields is poor and intensive chemotherapy protocols for differentiated tumors after chemotherapy will increase the risk of complications without obvious benefit. Pediatr Blood Cancer 2009;52:675–677. © 2008 Wiley‐Liss, Inc.     

Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor

BACKGROUND: The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. PATIENTS AND METHODS: In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. RESULTS: 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. CONCLUSION: Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.     

Epidemiology of Wilms tumor

Wilms tumor affects approximately one child per 10,000 worldwide before the age of 15 years. Incidence rates appear to be slightly elevated for U.S. and African Blacks in comparison to Whites, but are only half as great among Asians. Several case-control studies have suggested that paternal occupational or maternal hormonal exposures during pregnancy may increase the risk of Wilms tumor, but small numbers of subjects and inconsistencies in the patterns of exposures do not permit firm conclusions to be drawn. It is unlikely that such environmental exposures play a major role in the etiology of Wilms tumor. The median age-at-onset of Wilms tumor is 38 months in the U.S. National Wilms Tumor Study series, with cases in girls occurring on average 6 months later than in boys. Patients with bilateral tumors, aniridia, cryptorchism/hypospadias, Beck-with-Wiedemann syndrome, or intralobar nephrogenic rests tend to be diagnosed much younger than average (median 17–27 months). Those with familial disease or multicentric tumors have intermediate age-at-onset distributions, while those with perilo-bar nephrogenic rests are diagnosed at older ages. The epidemiologic features suggest that somatic mosaicism, rather than a germ-line mutation, may be responsible for some of the bilateral and multicentric cases. © 1993 Wiley-Liss, Inc.     

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??Childhood kidney tumors account for about 7% of all childhood cancers. Most childhood kidney tumors are Wilms tumor??but in the 15- to 19-year age group??most tumors are renal cell carcinoma. In medically developed countries??clinical trials in Wilms tumor??WT?? have resulted in overall survival rates of greater than 90%. Children’s Oncology Group Renal Tumor Committee??COG-RTC?? is one of the clinical study groups internationally known for its clinical research in childhood kidney tumor. Its standard treatment for children with Wilms tumor consists of initial nephrectomy??when feasible?? followed by chemotherapy and??in some patients??radiation therapy. This summary reviewed peer-reviewed??evidence-based reports about the treatment for Wilms tumor published recently and intended to be a resource to assist clinicians who care for children with Wilms tumor.     

Imaging of pediatric renal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper focused on Wilms tumor and nephrogenic rests

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.     

Recurrence of Wilms tumor after apparent cure

The recurrence of Wilms tumor after a 5-year disease-free interval is rare. We present two patients who had recurrent disease after a disease-free interval of greater than 7 years. Three additional patients, registered with the National Wilms Tumor Study who had a recurrence after 5 years, are also described. Of these three patients, two had nephroblastomatosis. Because more patients are achieving long-term survival, careful surveillance after apparent "cure" is recommended, particularly if nephroblastomatosis is identified in the original nephrectomy specimen.     

Complete necrosis induced by preoperative chemotherapy in Wilms tumor as an indicator of low risk: report of the international society of paediatric oncology (SIOP) nephroblastoma trial and study 9

BACKGROUND: The SIOP Nephroblastoma therapeutic protocols include a period of preoperative chemotherapy followed by nephrectomy and a period of postoperative chemotherapy. From the outset, identification of low-risk groups has been an aim of the SIOP Nephroblastoma Trials and Studies. Now that 90% of children with Wilms tumor can be cured, attention is even more focused on the identification of patients who could benefit from less aggressive postoperative therapy, thus minimizing the morbidity and late effects associated with treatment. The prognostic implications of total necrosis in nephroblastoma after chemotherapy have not been investigated hitherto. PROCEDURE: Between November 1, 1987 and June 30, 1993, 599 patients referred to the SIOP-9 Nephroblastoma Trial and Study were preoperatively treated and classified as stages I-IV nonanaplastic Wilms tumor. RESULTS: Of these 599 patients, pathologic examination of the nephrectomy specimen revealed a completely necrotic Wilms tumor (CNWT) with no viable tumor remaining in 59 (10%): these comprised 37 stages I-III and 22 stage IV. Of these patients, 58 (98%) had no evidence of disease at 5 years vs. 90% for the rest of the cohort (P < 0.05). Stages I-III patients represented 63% of CNWT and had a 97% overall survival rate. The only death was related to veno-occlusive disease and occurred in a stage I patient in the month following nephrectomy. Stage IV patients represented 37% of CNWT (vs. only 10% of all other cases of unilateral nonanaplastic Wilms tumor) and had a 100% rate of survival. Children with CNWT were older (mean 59 months vs. 43 months); their tumor at diagnosis was larger and had regressed more significantly at subsequent ultrasound examination. The data also uphold the hypothesis that Wilms tumors of blastemic pattern are most aggressive, but also are extremely responsive to chemotherapy. CONCLUSIONS: Patients with unilateral nonanaplastic WT that showed total necrosis following preoperative chemotherapy had excellent outcome and should benefit from less aggressive postoperative treatment in further trials. Other very responsive tumors, such as Wilms with <10% viable tumor, should also be assessed.     

Management of Wilms tumors in Drash and Frasier syndromes

Background

Children with WT1 gene‐related disorders such as Denys–Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end‐stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron‐sparing surgery was beneficial.

Procedure

We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007.

Results

We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate‐risk tumors and one high‐risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron‐sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft‐tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end‐stage renal disease‐related complications. The median follow‐up time for the 18 survivors was 136 months (range, 17–224 months).

Conclusion

Most Wilms tumors in children with WT1‐related disorders were early‐stage and intermediate‐risk tumors, with a young age at diagnosis. In patients without end‐stage renal disease, nephron‐sparing surgery should be considered for delaying the onset of renal failure. Pediatr Blood Cancer 2009;52:55–59. © 2008 Wiley‐Liss, Inc.     

Extrarenal Wilms tumour.

INTRODUCTION: Nephroblastoma is one of the most common solid tumours in children. It also is the most frequent tumour found in the kidneys. In 5 % of cases it affects both kidneys at the same time. About 70 - 80 new cases of Wilms tumour are registered in Poland annually, usually in patients aged from 1 to 7 years. Extrarenal Wilms tumours are extremely rare. Due to its rarity, series with more cases are based upon material collected from many clinical centers. AIM: We would like to present a case of a boy in whom we diagnosed nephroblastoma in the retroperitoneal space 14 years after he had completed a complex therapy for bilateral Wilms tumour. CONCLUSION: The development of an extrarenal tumour 14 years after complex treatment for bilateral nephroblastoma is related to the survival of metanephros located outside the kidney.     

Clinical presentation of rhabdoid tumors of the kidney

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.     

Renal functional reserve in long-term survivors of unilateral Wilms tumor.

We hypothesized that long-term survivors of unilateral Wilms tumor would have a decreased renal functional reserve secondary to the consequences of hyperfiltration in the nephrons of the remaining kidney. Therefore we evaluated the renal functional reserve in 12 long-term survivors of Wilms tumor after unilateral nephrectomy (mean +/- SE: 15 +/- 1.1 years; range 9 to 23 years). We measured the creatinine clearance before and after an acute, oral protein load to determine the renal functional reserve. Study subjects and control subjects were matched for age, gender, and body surface area. The basal creatinine clearances were similar (Wilms group 132 +/- 13 vs control group 142 +/- 11 ml/min/1.73 m2; p = not significant (NS]. There was no significant difference in the renal functional reserve between long-term survivors of Wilms tumor and matched control subjects (Wilms group 17 +/- 11 vs control group 25 +/- 11 ml/min/1.73 m2; p = NS). The change in creatinine clearance was not secondary to volume expansion because the fractional excretion of sodium was unchanged with protein loading (Wilms group before loading 0.92 +/- 0.12 vs after loading 0.99 +/- 0.13 (p = NS); control group before loading 0.91 +/- 0.12 vs after loading 1.0 +/- 0.14 (p = NS)). We conclude that up to 15 years after nephrectomy for unilateral Wilms tumor in childhood, there is no evidence of hyperfiltration injury.     

Extrarenal testicular Wilms’ tumor in a 3-year-old child

We report an extremely rare case of extrarenal testicular Wilms’ tumor in a 3-year-old boy with intrabdominal undescended left testis. The patient was admitted because of pain and vomiting, with evidence of a huge abdominal mass. At surgery a large tumor arising from the intrabdominal testis was found. Histology showed the classical triphasic Wilms’ tumor elements: epithelial, mesenchymal and blastemal areas. Extrarenal Wilms’ tumors account for only 3 % of all Wilms’ tumors and just ~100 cases have been reported in literature. Testicular origin is anecdotic. We present histomorphological, histogenetic, clinical, diagnostic, prognostic and therapeutic features of this rare tumor.     

Renal function after tandem high-dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor

Lee SH, Paik KH, Sung KW, Son MH, Yoo KH, Koo HH, Kim JY, Cho EJ. Renal function after tandem high‐dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. Pediatr Transplantation 2011: 15: 855–860. © 2011 John Wiley & Sons A/S. Abstract: Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high‐risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of β‐N‐acetylglucosaminidase and β2‐microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow‐up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor.     

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice.

BACKGROUND: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. METHODS: The available literature was reviewed. RESULTS: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. CONCLUSIONS: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.     

Expression of WT-1, Bcl-2, and CD34 by Primary Renal Spindle Cell Tumors in Children

The confident diagnosis of renal spindle cell tumors in children is often difficult. An immunohistochemical study of WT-1, Bcl-2, and CD34 was performed to determine their expression profiles and to assess the potential utility of these immunohistochemical markers in the differential diagnosis of 36 cases of renal spindle cell tumors of childhood. The cases included 11 stromal predominant Wilms tumors, 12 cellular mesoblastic nephromas, 9 clear cell sarcomas of the kidney (CCSK), and 4 monophasic synovial sarcomas. WT-1 was uniformly positive in primitive undifferentiated stromal Wilms tumors (6 of 6) and negative in the differentiating and differentiated stromal elements of Wilms tumors (0 of 5). WT-1 was also negative in cellular mesoblastic nephromas (0 of 12), CCSKs (0 of 12), and synovial sarcomas (0 of 4). Bcl-2 was expressed in all stromal Wilms tumors (11 of 11), all synovial sarcomas (4 of 4), some CCSKs (4 of 9), and none of the cellular mesoblastic nephromas (0 of 12). Although CD34 was absent in the tumor cells of all the tumors studies (0 of 36), CD34 immunohistochemistry nicely demonstrated the evenly distributed septal capillaries characteristic of CCSK in all 9 cases of this tumor. We conclude that a combination of WT-1 and Bcl-2 immunohistochemistry may aid in the distinction of stromal Wilms tumor, monophasic synovial sarcoma, cellular mesoblastic nephroma, and CCSK.     

Recent advances in Wilms tumor genetics

The past decade has witnessed substantial growth in our knowledge of the genes and loci that are altered in Wilms tumor. Although Wilms tumor was one of the original paradigms of Knudson's two-hit model of cancer formation, it has become apparent that several genetic events contribute to Wilms tumorigenesis. Recent research has identified targets and regulators of the first Wilms tumor gene, WT1, has uncovered several candidate genes at the second Wilms tumor locus, WT2, and has identified two familial Wilms tumor loci, FWT1 and FWT2. The recent discovery of activating beta-catenin mutations in some Wilms tumors has also implicated the Wnt signaling pathway in this neoplasm. Recurrent abnormalities of other loci, including 16q, 1p, and 7p, have indicated that these sites may harbor Wilms tumor genes. An enhanced understanding of these and other genetic lesions will provide the foundation for novel targeted Wilms tumor therapies.     

Renal cell carcinoma as a second malignant neoplasm in a patient with non-syndromic hemihypertrophy and previous Wilms tumor

Survivors of childhood Wilms tumors are at an increased risk of second malignant neoplasms. Recently, it has been postulated that renal cell carcinoma is among the malignancies for which this population is at risk. We present the unique case of an adult Wilms tumor survivor with non-syndromic hemihypertrophy (NSHH) who developed renal cell carcinoma. This case highlights the need for close follow-up in two populations: adults who have survived Wilms tumor and those with NSHH.     

COX-2在肾母细胞瘤中的表达及意义

目的通过研究COX-2在肾母细胞瘤中的表达，探讨COX-2与肾母细胞瘤的关系。方法应用免疫组织化学SABC法柃测25例肾母细胞瘤患儿肿瘤组织标本及10例瘤旁肾组织标本（距肿瘤边缘2cm的肾组织标本）中COX-2的表达情况。结果COX-2在肾母细胞瘤中阳性表达率为84％，对照组阳性表达率为10％，两者比较，差异有统计学意义（χ^2=16．753，P〈0．001）。伴有淋巴结转移的肾母细胞瘤患儿淋巴结COX-2阳性表达率高于无淋巴结转移者（χ^2=9．000,P〈0．01）。COX-2的阳性表达率随临床分期的增加而增高。COX－2的阳性表达率与肾母细胞瘤的临床分期呈正相关（r=0．966，P〈0．05）。结论COX－2的阳性表达率有随肾母细胞瘤临床分期的升高而增高的趋势，提示COX-2可能参与了肾母细胞瘤的发生发展过程，可为肾母细胞瘤的治疗和预防开辟新的途径。