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.     

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.     

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.     

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.     

Case report of a Wilms' tumor and a left-sided inferior vena cava. A common tumor with a normal variant of surgical significance

We report a case of a successful surgical resection of a Wilms' tumor in the right kidney with a coincidental preoperative imaging finding of a left-sided inferior vena cava. To our knowledge, these 2 conditions occurring together has not been previously reported in literature. Diagnostic features and the value of magnetic resonance imaging are emphasized. We also review the literature of major venous anomalies and their influence on surgical procedures carried out on such patients.     

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.     

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.     

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     

Anaesthetic management of a patient with the intracardiac extension of Wilms' tumour

Summary Wilms' tumour (nephroblastoma) is known to invade the inferior vena cava and extend to the intracardiac chambers. We describe the treatment and surgical removal of the intracardiac extension of a Wilms' tumour using cardiopulmonary bypass in a 4-year-old girl. Techniques to avoid paradoxical embolism in the presence of a patent foramen ovale and to deal with excessive hepatic venous blood flow using the Pringle manoevre (hepatic inflour occlusion) are described. Good communication between anaesthesiologists, surgeons and perfusionists was indispensable. The anaesthesiologist is an important member of the team during performance of a complicated procedure.     

Predictors of surgical outcome in Wilms' tumor: a single-institution comparative experience

Background

The merits of primary nephrectomy (PN) vs preoperative chemotherapy (PC) for patients with Wilms' tumor (WT) are much debated. Early data from the International Society of Pediatric Oncology suggested decreased intraoperative spillage but increased risk of local recurrence after PC. Patients with WT at our institution were managed with PC until 1996; subsequently, they underwent PN. This study compares these approaches as they affect tumor spillage, local recurrence, and survival.

Methods

Patients with WT diagnosed at the Hospital for Sick Children from 1985 to 2003 were reviewed.

Results

One hundred sixty patients were identified (114 PC and 46 PN). Tumor spill occurred in 6 (5.3%) of 114 PC and 2 (4.3%) of 46 PN patients. Tumor inhomogeneity, tumor size, and inferior vena cava compression/clot at diagnosis did not affect incidence of spill. Of 6 PC patients with surgical spill, 1 (17%) had significant tumor shrinkage, compared with 87 (81%) of 108 without spill (P < .001). Preoperative chemotherapy and PN had equal rates of surgical complications. Preoperative chemotherapy resulted in 12 (10.5%) of 114 local recurrences vs 5 (10.8%) of 46 with PN. Event-free survival and overall survival were 80% and 92% for PC at 129 months vs 85% and 96% for PN at 61 months.

Conclusions

Preoperative chemotherapy and PN are equally effective in the treatment of WT with no difference in tumor spillage. Failure of the tumor to shrink in size with PC was significantly associated with an increase in tumor spillage and would suggest that a more cautious surgical approach be undertaken in these cases.     

Progress of fundamental research in Wilms' tumor

The progress of fundamental research on the histopathological and molecular genetic properties, model systems, growth factor involvement, and tumor markers of clinical nephroblastoma (Wilms' tumor) are reviewed. Histologically, Wilms' tumor (WT) has been found to reveal a disorganized renal developmental process in which blastema and epithelia are randomly interspersed in varying amounts of stroma. Anaplasia is the only criterion for assigning a WT as having an unfavorable histology. Cytogenetic analysis identified WT genes at chromosome 11p13 (WTI), 11p15 region (WT2), and 16q (WT3). Permanent in vitro WT cell lines and in vivo WT models, such as human xenografts, have been established which provide indefinite sources of tumor material for fundamental, as well as therapy-directed, research. Abnormalities of growth factor (GF) expression in WT indicate that GF may play an important role in WT pathogenesis. A series of monoclonal antibodies was tested in WT by immunohistochemical techniques to identify specific diagnostic and prognostic markers. p53 expression in anaplastic WT is significantly higher than in differentiated WTs, indicating p53 may be a prognostic marker. Although significant progress has been made in the fundamental research, our basic knowledge of this malignancy is still limited. The availability of suitable experimental models, particularly the human xenograft system, offers the opportunity for further study of the cell biological and molecular aspects of WT and its clinical progression.     

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.     

Long-term follow-up after unilateral nephrectomy and radiotherapy for Wilms' tumour

Twenty-nine patients who had had unilateral nephrectomy for Wilms' tumour in one hospital were known to have survived more than 12 years. Sixteen agreed to attend for clinical review, of whom 14 had estimation of serum creatinine, 24-h urine protein excretion and endogenous creatinine clearance. The follow-up period was 13–26 years (median 17 years). All but one had had radiotherapy and all had chemotherapy (actinomycin D, 16; vincristine, 5). Some degree of kyphoscoliosis was present in all except the patient who did not receive radiotherapy. Four patients had diastolic blood pressure 90 mmHg or greater. Two patients had mild proteinuria (392, 361 mg/day). Serum creatinine ranged from 53 to 125 mol/l and endogenous creatinine clearance ranged from 39 to 173 ml/min (median 81, mean 89). Of the 7 patients who were 20–26 years postnephrectomy, 2 were hypertensive and 1 had elevated urinary protein excretion. We conclude that the long-term prognosis of unilateral nephrectomy in childhood is good.     

Intrarenal pelvic papillary Wilms'' tumor associated with aniridia: A case report

BACKGROUND: Intrarenal pelvic Wilms' tumor in a papillary growth is rare in children. A case of a two-year-old infant with Wilms' tumor associated with congenital aniridia is reported. RESULTS: A chromosomal abnormality (11p13 deletion) was found in this patient. The tumor was well evaluated by ultrasonography, computed tomography and magnetic resonance imaging. DISCUSSION: Previous case reports are briefly reviewed and the clinical characteristics disclosed.     

Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumor

Purpose

Loss of pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, has been linked to progression of angiogenesis-dependent diseases. We postulated that decreased levels of endogenous PEDF in the kidney creates a tumor permissive environment for Wilms' tumor.

Methods

Fresh and frozen Wilms' tumor (n = 28), adjacent (n = 3), and normal kidney (n = 8) were immunostained and graded. The Wilms' tumor cells (SK-NEP-1), renal epithelial cells (NRK-52), and fresh tumor samples were grown in culture. Condition media were collected and analyzed by an in vitro angiogenesis assay and Western blot. The SK-NEP-1 cells were treated with PEDF and cell viability assessed.

Results

Wilms' tumors expressed less PEDF than normal and adjacent kidney. Pigment epithelium-derived factor protein secretion was abundant in NRK-52 cells but significantly decreased in Wilms' tumor. Pigment epithelium-derived factor acted as blockade to angiogenesis and it had a dose-dependent cytotoxic effect on Wilms' tumor epithelial cells.

Conclusion

Renal tubular epithelial cells are a rich source of PEDF in the normal kidney. Reduced levels of PEDF in Wilms' tumor remove a critical endogenous renal barrier to angiogenesis and tumor cell survival. Therapeutic replacement of PEDF may prove to be an effective strategy to combat Wilms' tumor progression.     

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.     

Bilateral Wilms' tumors with progressive or nonresponsive disease

Background

To provide guidelines for future cooperative group trials, we reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive disease (PNRD).

Methods

NWTS-4 enrolled 3335 patients from August 1986 to September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data were collected on patients with BWT. Treatment guidelines were outlined in the protocol, but patients were not on study.

Results

Thirty-eight children with BWT had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2-29 months) before definitive resection. After the initial chemotherapy regimen, 36 children went on to a second regimen, and of these, 21 children received a third regimen before resection. Eleven patients received irradiation to one or both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in 3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before resection. A fourth patient developed a diffusely anaplastic tumor 13 months after therapy. Other pathological findings included rhabdomyomatous (4 patients) or differentiated stromal elements (10 patients) and complete necrosis (1 patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology review of those specimens.

Conclusions

BWT patients with PNRD received prolonged courses of chemotherapy. Early and sequential biopsies to establish the reason for failure to respond should be obtained. This will identify anaplastic tumors managed best by early nephrectomy and intensive chemotherapy and will also distinguish differentiated tumors that are best managed with early resection, but less intensive therapy after nephrectomy.     

Adult Wilms'' tumor mimicking hemorrhagic renal cyst

A 36-year-old man presented with macroscopic hematuria associated with right flank pain. Examination of the patient revealed a cystic mass in the right kidney. Because the mass had increased in size, enucleation of the mass was performed. Histopathological findings revealed nephroblastoma, therefore, radical nephrectomy was performed. We believe the pathogenesis of the cystic formation to be a process in which a tumor that had developed in the pericalyceal region spontaneously ruptured, exuding urine into the perinephric space, forming a cystic mass. The patient is alive with no evidence of disease 24 months after the operation.     

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.