Bilateral Wilms' tumors: a single-center experience with 19 cases

Background/Purpose

Bilateral Wilms' tumors present a therapeutic challenge, particularly with delay in presentation, when there is poor response to chemotherapy and when associated with nephroblastomatosis. The primary aim of management is eradication of neoplasm, while at the same time preserving of renal function.

Methods

Nineteen bilateral Wilms' tumors were seen in our service between 1981 and 2003. This represented 10% of the 190 patients with Wilms' tumors seen during this period. There were 12 female and 7 male patients ranging in age from 7 months to 8 years. Fourteen had synchronous presentation, one of whom had liver metastasis at diagnosis. Of the 5 patients with metachronous tumors, 3 had their initial nephrectomies done elsewhere. Nephroblastomatosis was identified in 18 (95%) of the patients. Treatment was, in most cases, according to National Wilms Tumor Study Group protocols, with initial bilateral biopsy, neoadjuvant chemotherapy, and tumorectomy. Where indicated, nephrectomy (partial or complete) involved using ice dam topical cooling and vascular control, and in one case, bench surgery and extensive renal reconstruction with orthotopic autotransplantation. Revision tumorectomy was used on 3 occasions for recurrence in areas of nephroblastomatosis. There were 6 extrarenal relapses.

Results

Ten patients are alive and free of disease 1 to 15 years after treatment, all with well preserved renal function (lowest recorded glomerular filtration rate was 85 mL/min per 1.73 m²). Nine have died (2 of unrelated disease), including 6 of the 7 with spread outside the kidney. All 3 with unfavorable histology are alive. Of the 5 with metachronous presentations, 4 are alive, as are 7 of 10 who presented in the last decade.

Conclusions

Appropriate chemotherapy and conservative nephron-sparing and innovative surgery can achieve good results with preservation of adequate renal function in nearly all cases. Nephroblastomatosis was an almost universal finding and requires close monitoring because Wilms' tumors developed in residual suspect areas. Revision surgery was effective. Unfavorable histology did not have a reduced survival in our series. Metastatic spread outside the kidney had a poor prognosis.     

Bilateral intrarenal pelvis Wilms' tumor with fibroepithelial polyp

Intrarenal pelvis Wilms' tumor is rare in children. A case of a 28-month-old boy with bilateral intrarenal pelvis Wilms' tumor associated with a fibroepithelial polyp is reported in this article. The tumor was evaluated by ultrasonography, computed tomography, and intravenous pyelography. The boy underwent bilateral renal pelviotomies. Now he is being treated and followed up by pediatric oncologists.     

Bilateral Wilms' tumor and secondary malignancies

A series of six patients with bilateral Wilms' tumor (nephroblastoma) is presented. Multimodal therapy yielded a survival rate of 83% at 2 yr of follow-up. However, at the end of a later follow-up period only two patients (33%) were alive. of the 4 patients who died. Only 1 died of Wilms' tumor. One died of complications of aggressive chemotherapy and two patients died after 12 and 16 yr following treatment of secondary malignant tumors arising in the irradiated region. Patients with bilateral tumor should be followed at regular intervals for the duration of life for the occurrence of secondary malignant tumors.     

Renal tumors in the second decade of life: results from the California Cancer Registry

Background

Renal tumors are rare in adolescents and young adults. The aim of this study was to characterize the histologic condition, epidemiology, and survival of renal tumors in patients aged 11 to 20 years old using a large, population-based database.

Methods

The California Cancer Registry was reviewed from the years 1988 to 2004. All renal tumors in patients aged 11 to 20 years old were identified. The data were analyzed with relation to patient age, sex and ethnicity, tumor histologic examination, and actuarial mortality rates.

Results

Seventy-seven primary renal malignancies were identified. Thirty-nine (51%) were renal cell carcinoma, 23 (30%) were Wilms' tumor, and 15 (20%) were other tumor types. The mean age of the patients with renal cell carcinoma was 16.7 years old, which was significantly older than the Wilms' tumor patients (13.9 years; P < .01). The 5-year cumulative survival rate of patients with renal cell carcinoma was 54%, which was worse than that of Wilms' tumor patients (77%).

Conclusion

Primary renal malignancies are uncommon in the second decade of life. The most common tumor type in this age-group is renal cell carcinoma followed by Wilms' tumor. Patients with renal cell carcinoma tend to be older and have a lower survival than patients with other kidney tumors.     

Wilms' tumor

In the last 2 decades, important advances in the treatment of Wilms' tumor have been made. The remarkable improvement in survival in these patients has been the product of new surgical techniques, classification of the tumors into prognostic stages upon initial presentation and the tailoring of chemotherapy and radiation therapy thus permitted. A brief historical perspective is presented with a review of the current treatment and ongoing studies.     

Teratoid Wilms' tumor: a case report with literature review

Teratoid Wilms' tumor is an unusual histologic variant of nephroblastoma in which the heterologous tissue predominates. The treatment for this tumor has not been established because of its rarity and varying tumor components. The authors report a case of localized teratoid Wilms' tumor in a 4-month-old female infant successfully treated with nephrectomy only. The tumor originated from the right kidney with multiple cysts and calcifications; renal teratoma was suspected preoperatively, and the operation was performed. The tumor was excised completely, and the specimen weighed 340 g. Histopathologic examination showed that various teratoid elements occupied most of the tumor with sparse islands of triphasic nephroblastoma, which was consistent with teratoid Wilms' tumor. Anaplastic elements, tumor capsule invasion, renal sinus soft tissue invasion, or tumors in intrarenal vessels were not observed. The patient was disease free for 3 years after surgery without receiving chemotherapy. We selected this therapeutic approach because of the chemoresistance of this tumor and the excellent prognosis in small (<550 g) stage I/favorable-histology classical Wilms' tumor diagnosed at less than 24 months of age. Therefore, nephrectomy alone may be an acceptable treatment of this stage of tumor in patients with teratoid Wilms' tumor.     

The value of surgery in directing therapy for patients with Wilms' tumor with pulmonary disease. A report from the National Wilms' Tumor Study Group (National Wilms' Tumor Study 5)

Background/Purpose

Computed tomography (CT) of the chest with its increased sensitivity frequently identifies lesions not visible on chest radiograph. Treatment of such lesions is controversial. A recent review suggests that patients with Wilms' tumor with pulmonary lesions detected only by CT, who were treated with dactinomycin and vincristine, have an inferior outcome compared with those who also received pulmonary radiation therapy (RT) and doxorubicin. It is important to determine if these small lesions seen only on CT represent metastatic disease and whether patients with these lesions require RT and/or doxorubicin for optimal outcome.

Methods

Patients with Wilms' tumor with lung metastasis, registered on National Wilms' Tumor Study 5, were reviewed, and those with CT-only lesions who had a radiology and surgical checklist submitted were identified. The treatment regimens of these patients and the histological findings of the pulmonary lesions are presented. We analyzed the pathological findings by whether the patients had single or multiple lesions.

Results

Of 2498 patients registered on National Wilms' Tumor Study 5, 252 had pulmonary metastases. Of these patients, 129 (5.2%) had CT-only lesions (<1 cm). Forty-two of these patients (20 boys and 22 girls) underwent lung biopsy at the discretion of the attending physicians. The local tumor stages in these patients were stage I (7%), II (34%), and III (59%). The treatment stages in these patients were stage I (n = 3, 2 drugs), II (n = 3, 2 drugs), III (n = 12, 3 drugs); and IV (n = 24, 3 drugs + RT). There were 16 patients with isolated lung lesions and 26 with multiple lesions, average size 5.8 ± 0.5 mm. Of 16 isolated lesions, 13 patients (82%) and 69% (18/26) with multiple lesions had tumor on biopsy. Of the 24 who received RT, 8 had a negative biopsy and, thus, may not have needed the RT. Five of 6 treated with just 2 drugs may have been undertreated. Nine of 12 treated with 3 drugs had tumor on biopsy.

Conclusions

Computed tomography-only pulmonary lesions are not invariably tumor, demonstrating the need for histopathological confirmation. Biopsy remains critical until radiographic techniques allow differentiation between benign and malignant lesions to optimally direct therapy.     

Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor Study

Purpose

The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy.

Methods

One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined.

Results

Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys.

Conclusions

Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.     

Teratoid Wilms' tumor: case report of a rare variant that can mimic aggressive biology during chemotherapy

Teratoid Wilms' tumor is considered by some as a variant of Wilms' tumor containing at least 50% heterologous differentiated tissue. Fewer than 30 cases have been described. We report a 9-month-old boy with bilateral Wilms' tumors who did not respond to multiagent chemotherapy and underwent right nephrectomy that showed a teratoid Wilms' tumor. The patient continued to survive despite cessation of treatment. The overall predominance of differentiated stromal elements in this subtype of Wilms' tumor might explain the poor response to chemotherapy yet generally favorable outcome. Recognition of this subtype on biopsy might justify earlier surgical intervention that, for bilateral tumors, might allow for greater nephron sparing.     

Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG)

Background

Extension of Wilms' tumor into the ureter is a rare event. We reviewed the National Wilms' Tumor Study Group (NWTSG) database to define the clinical presentation, associated pathologic features, and clinical outcome of these patients.

Methods

Records of children identified to have ureteral extension of Wilms' tumor enrolled in NWTS-3, 4, and 5 were reviewed. Presenting symptoms, diagnostic studies, histopathologic findings, operation performed, and outcome were recorded. The NWTS-5 surgical data were prospectively collected as part of the quality assurance program.

Results

Forty-five children were identified with ureteral extension. For NWTS-5, the incidence of ureteral extension was 2%. Clinical presentations were gross hematuria in 22 patients, 2 had passage of tissue per urethra, and 1 child had a urethral mass. The remainder had nonspecific presentations. Ureteral extension was seen on preoperative imaging in 14 patients, intraoperatively in 22, and on pathologic examination in 9 patients. Hydronephrosis was noted in 12 patients, and there was nonfunction of the kidney in another 8. Laterality of the tumor was right side in 26 and left in 19. Cystoscopy was performed in 12 children. Findings included tumor seen at the ureteral orifice in 6 patients and bleeding from the orifice in one child. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 patients, including 2 of the 7 with separate removal of the ureteral extension. The number of patients in each clinical stage was as follows: stage I, 10; stage II, 18; stage III, 14; and stage IV, 3. The tumor extended into the proximal ureter in 23 patients, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. The level of ureteral extension was not clearly noted in the 45th child. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. There were 3 deaths because of tumor in patients with unfavorable histologic tumors, and 1 because of treatment toxicity in a child with favorable histologic findings.

Conclusions

Ureteral extension occurs in approximately 2% of patients with Wilms' tumor. The diagnosis should be suspected in patients with gross hematuria, hydronephrosis, or nonfunctioning kidney. Cystoscopy with retrograde ureterogram may aid in preoperative diagnosis in these patients. Preoperative diagnosis is important because complete resection of the involved portion of ureter at the time of nephrectomy can avoid residual disease and the need for second surgery or radiation therapy.     

Wilms' tumor arising within a mediastinal teratoma

The majority of Wilms' tumors present in young children as an intraabdominal mass of renal origin. The use of multimodal treatment protocols according to internationally recognized treatment guidelines has resulted in extremely high cure rates even in the setting of advanced disease. By comparison, Wilms' tumors in older patients or Wilms' tumors located entirely outside the kidney are extremely rare. Because of the rarity of these tumors and the lack of established treatment guidelines specific to these lesions, older patients with atypical Wilms' tumors are at risk for under treatment and poorer outcomes. We report the case of an 18-year-old man with a Wilms' tumor arising within a mediastinal teratoma and discuss the management of this extremely rare lesion.     

Survival in bilateral Wilms' tumor--review of 30 National Wilms' Tumor Study cases.

Bilateral tumors were found in 33 patients or 5.4% of 606 children enrolled in the National Wilms' Tumor Study. Twenty six of 30 patients (87%) for whom detailed clinical information is available survived 2 yr after conservative surgery and radiation therapy. All patients were given one or more chemotherapeutic agents. A variety of surgical procedures were used including biopsy only, nephrectomy, and partial nephrectomies. Radiation therapy doses ranged widely, but between 1000 and 2000 rad apparently sufficed for local control in most cases. Recommendations regarding management by surgery, radiation therapy, and chemotherapy are given.     

Bilateral multifocal Wilms' tumor

A three-year-old boy who presented with symptoms of peritonitis was found to have four Wilms' tumors affecting both kidneys. Individual enucleation of three tumors in the right kidney plus left lower nephrectomy were performed. Chemotherapy was administered for one year. The diagnosis of Wilms' tumor was confirmed on each specimen by the histologic studies. The child remains asymptomatic and developing normally six years after the initial surgical treatment. Bilateral partial nephrectomies is the most conservative of the surgical treatments available for bilateral Wilms' tumor.     

Renal function and outcome following salvage surgery for bilateral Wilms' tumor

Purpose

Maintaining adequate renal function without compromising cure in children with bilateral Wilms’ tumor is surgically demanding and challenging. The aim of this study was to assess renal function and outcome in children treated in one institution for bilateral Wilms’ disease by renal salvage procedures.

Methods

This study is a retrospective review of all patients with histologically proven bilateral nephroblastoma who underwent a renal salvage procedure between November 1973 and June 2002. The median follow-up time was 52 months (range, 8 to 326 months).

Results

Twenty-three patients were included in the study. The median age at diagnosis was 19 months (range, 5 to 65 months). Patients who presented before 1982 (n = 5) were treated surgically first followed by chemotherapy. The remainder (n = 18) received initial chemotherapy before the operation. Of the 46 kidneys, 18 had a nephrectomy. The remaining 28 underwent a renal salvage procedure. At follow-up, 19 patients had good renal function, 2 had satisfactory function, and 2 had renal failure. Seventeen of the 23 children are alive and tumor free at follow-up (74%). Four children died of distant metastases and 2 of renal failure. Local recurrence in the salvaged kidney was detected in 1 patient 12 years after surgery after the commencement of immunosuppression for renal transplantation.

Conclusions

These results confirm that renal salvage procedures, in combination with chemotherapy, are a safe and effective way of treating children with bilateral Wilms’ disease. In addition, renal salvage surgery can maintain satisfactory renal function in the majority of these patients without an increased risk of local recurrence. When transplantation is required, the remaining native kidney should be removed to prevent tumor recurrence.     

The use of preoperative chemotherapy in Wilms' tumor with contained retroperitoneal rupture

Purpose

The National Wilms Tumor Study currently describes 3 indications for the use of preoperative chemotherapy: extensive caval involvement, bilateral tumors, and patients who only have a single kidney. However, the management of patients who present with a contained retroperitoneal rupture is not specifically addressed. This is relevant because of the strong possibility of peritoneal contamination when performing a primary resection and the resultant requirement for total abdominal radiation. The use of neoadjuvant chemotherapy in this subgroup of patients may be warranted.

Methods

We retrospectively reviewed our experience with Wilms' tumor and identified 3 cases with contained rupture at presentation. Details of their initial evaluation and therapy, resection and pathologic findings, and follow-up constitute this report. Institutional review board waiver was obtained for the purposes of this review.

Results

Two male patients, aged 2.9 years, and 1 female patient, aged 9.3 years, were identified. All patients received preoperative chemotherapy with vincristine and dactinomycin (n = 1) plus doxorubicin (n = 2) for 4 to 6 weeks before surgical resection. One patient underwent pretreatment computed tomography-guided biopsy of the kidney mass for diagnostic purposes. Presurgical computed tomographic scans showed resolution of perinephric blood and fluid with tumor shrinkage. Histopathologic analyses showed all tumors were resected with negative margins, and there was no intraoperative tumor spillage. All patients received 1050 to 1080 cGy of flank radiation postoperatively. All patients are currently alive at follow-up without evidence of local recurrence or distant disease.

Conclusions

Neoadjuvant chemotherapy allowed for complete resection and avoidance of total abdominal radiation in 3 patients with ruptured Wilms' tumor and hematoma within the retroperitoneum. These data support the use of initial chemotherapy in children with retroperitoneal rupture and hematoma of Wilms' tumor at diagnosis.     

Diagnosis of Wilms' tumor using near-infrared Raman spectroscopy

Purpose

Raman spectroscopy has distinguished malignant from normal tissues in several types of cancer. This is the first report of applying Raman spectroscopy to the diagnosis of Wilms' tumor.

Methods

Specimens of normal kidney, Wilms' tumor, xanthogranuloma, nephrogenic rests, and rhabdoid tumor were collected fresh from the operating room. Specimens of Wilms' tumor, normal kidney, and congenital mesoblastic nephroma were retrieved from the cryobank and thawed to room temperature. At least 12 Raman spectra were collected from each tissue sample. Histologic slides of each specimen were reviewed by pediatric pathologists. A computer algorithm based on discriminant function analysis (DFA) classified the Raman spectra of Wilms' tumor and the normal sample.

Results

Four hundred sixty-seven spectra were collected from 41 specimens. Using DFA, Raman spectroscopy differentiated Wilms' tumor from normal with 100% sensitivity and specificity and treated from untreated Wilms' tumor with 100% sensitivity and specificity. Using a DFA model built from cryopreserved specimens but applied to fresh Wilms' and normal samples, the sensitivity and specificity were 93.3% and 90.9%, respectively.

Conclusion

Raman spectroscopy is an accurate technique for differentiating Wilms' tumor from normal kidney and treated from untreated Wilms' tumor. It has potential to diagnose in minutes what currently takes several hours to days.     

Treatment of bilateral Wilms' tumors--a 22-yr experience

A total of 157 children with Wilms' tumors were treated at the Children's Memorial Hospital during the years 1956-1978. Fourteen (or 9%) of these children had bilateral lesions. During the early years, treatment consisted of surgical excision of one kidney with radiation to the second tumor. During the second decade of this study a more aggressive approach to bilateral tumors was used consisting of nephrectomy on the side of the large tumor, with a heminephrectomy on the contralateral side and chemotherapy. More recently, we have attempted bilateral heminephrectomy when possible, together with increasingly aggressive chemotherapy. This series of patients allows us to compare the results of various treatment modalities among our own patients as well as those reported from other pediatric surgical centers.     

Adult Wilms' tumor: clinical characteristics of four cases and review of the literature

Adult Wilms' tumor (AWT) is a rare disease. We investigated the clinical characteristics and the outcome of four patients with AWT treated by nephrectomy followed by radiation therapy and/or chemotherapy (protocol of the Fourth National Wilms' Tumor Study). Serum levels of lactic dehydrogenase (LDH), immunosuppressive acidic protein (IAP), and C-reactive protein (CRP) were above normal in all four patients. Two of three patients with unfavorable histology (UFH) had stage III or IV disease and died within 14 months of diagnosis while undergoing the chemotherapy. The other patient with UFH had a stage II tumor, which was treated with tumor-bed irradiation, and has survived for 26 months after nephrectomy. One patient with a stage I tumor and favorable histology also received chemotherapy, but she subsequently developed multiple metastases, and died 70 months after nephrectomy. Radiotherapy for metastases had palliative effects on osseous pain and tumor growth. The clinical results of the chemotherapy for AWT were poor. Analysis of more cases is needed to indicate whether or not the conventional chemotherapeutic regimen for Wilms' tumor in children requires modification to improve the outcome in AWT. Received: February 22, 1999 / Accepted: July 23, 1999