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.     

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.     

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.     

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.     

Recent experience with Wilms' tumor: 1978–1991

Background: The treatment of Wilms' tumor has undergone major advances in the past four decades. Current therapy is based on both the stage and pathology of the tumor. We have reviewed our recent experience with this tumor to assess the results of treatment on protocols that generally avoid the use of doxorubicin. Methods: Between January 1978 and December 1991 we treated 114 children with renal tumors. Ninety-one (80%) had favorable histology Wilms' tumor and 23 (20%), unfavorable histology tumors (13 anaplastic Wilms' tumors, four clear cell tumors of the kidney, and six sarcomatous tumors with rhabdoid elements). Chemotherapy was divided into two eras: 1978–1982 (vincristine and actinomycin-D) and 1983–1991 [vincristine and actinomycin-D for all patients, and cyclophosphamide for those with favorable histology and metastatic disease (n=13) and all patients with anaplastic histology (n=13)]. Four patients with clear cell or rhabdoid/sarcomatous tumor, three of whom are disease-free, were treated with a five-drug regimen (vincristine, doxorubin, cyclophosphamide, platinum, and VP-16). Approximately two thirds of the patients received megavoltage radiotherapy to the tumor bed. Mean abdominal radiation doses from 1978 to 1982 were slightly higher than those used from 1983 to 1991 (2,597±782 cGy vs. 2,039±524 cGy, respectively). Results: No isolated local failures were observed in any favorable histology patient who received radiotherapy. Among the 91 patients with favorable histology, there was no statistically significant difference in event-free survival irrespective of stage. Outcome for patients with anaplastic or clear cell variants was not different from that for those patients with favorable histology, but there were only small numbers in these groups for comparison. Only children with a rhabdoid/sarcomatous variant demonstrated survival that was different from all others (p=0.00). Our previously reported patients with stage I tumors (<550 g) (n=11) who were treated by nephrectomy only continue to have an excellent outcome (survival 100%). Conclusions: Wilms' tumors remain highly curable. Some unfavorable histology tumors require intensive therapy. Others such as our stage I tumors may be best observed without adjuvant therapy to avoid the toxicity of treatment.The results of this review were presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

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.     

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目的探讨原发性腹膜后内胚窦瘤的治疗和预后方法回顾性分析1991～2002年收治的11例碍发性腹膜后内胚窦瘤．结果该组病例占同期收治恶性原发性腹膜后肿瘤的8.8％(1l／125)和内胚窦瘤的20.3％(1l／54)。术前B超、CT或MR1检查发现腹膜后肿瘤。术前血清甲胎蛋白升高5例全组手术切除全部或大部分肿瘤。术后用PVH(顺铂、长春新碱、博菜霉素)或BEP方案(博菜霉素、足叶乙甙、顺铂)化疗随访8个月至8年，生存10例，死亡1例。结论以顺铂为基础的联合化疗改善了内胚窦瘤的疗效，测定血清AFP确助内胚窦瘤的诊治，应选择恰当的手术方式并辅以联合化疗来救治病人     

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.     

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.     

原发性腹膜后巨大肿瘤的手术经验

目的总结原发性腹膜后巨大肿瘤的外科手术经验。方法回顾性分析1998~2002年18例腹膜后巨大肿瘤手术治疗的临床资料。结果14例完整切除,1例大部切除,3例剖腹探查加活检术。14例恶性肿瘤中有10例完整切除,其中8例行联合脏器切除;4例良性肿瘤均完整切除,其中1例行联合脏器切除,无手术死亡。随访3年,18例中14例健在,死亡4例,肿瘤复发14例。结论准确的术前评估、恰当的手术径路、良好的手术技能是提高手术切除率的关键。     

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.     

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.     

Strategy for management of retroperitoneal tumors with caval tumor thrombus

The surgical management of retroperitoneal tumors extending into the inferior vena cava (IVC) can be challenging. Although Wilms' tumor is the most common retroperitoneal tumor extending into the IVC, one must approach these tumors systematically as other diagnoses are possible. We present 4 consecutive cases of retroperitoneal tumors with IVC extension as a basis for a management strategy in approaching these patients. Despite similar presentations, these cases illustrate the nuances in surgical management and need for multidisciplinary care with the pediatric oncologists, pediatric surgeons, and pediatric cardiac surgeons.     

原发性腹膜后肿瘤107例治疗与预后分析

目的 提高原发性腹膜后肿瘤的诊断及治疗水平。方法 回顾性分析1996—2005年107例原发性腹膜后肿瘤的临床治疗与随访结果。结果 原发性腹膜后肿瘤良、恶性之比0．68：1。手术治疗96例，完整切除58例，联合切除25例，部分姑息切除13例。良、恶性肿瘤的预后比较差异有显著性（P〈0．001），恶性肿瘤部分与完整切除病例的预后差异有显著性（P〈0．05）。结论 原发性腹膜后肿瘤较少见，应予以足够重视。B超、CT检查有助于腹膜后肿瘤的诊断。早期诊断与施行根治性切除是有效治疗方法，可显著提高存活率。     

Isolated endobronchial metastasis of Wilms' tumor

Isolated endobronchial metastasis from extrapulmonary solid organ was rarely reported in previous literature. We report an isolated endobronchial metastasis of Wilms' tumor in a 4-year-old boy. He underwent right nephrectomy on account of Wilms' tumor at the age of 3 years. We performed a wedge resection of a metastasis to the right lower lobe of the lung a year later, followed by chemotherapy and irradiation of the involved lung over a period of 30 weeks. One and a half years later, he developed obstructive pneumonitis of the left lung. Fiberoptic bronchoscopy identified a tumor at the left main bronchus with near total bronchial obstruction, compatible with findings on a computed tomographic scan. Rigid bronchoscopy was performed to core out the obstructing tumor. It was reported as a metastatic Wilms' tumor. Successful reexpansion of the left upper lobe was achieved and he was discharged uneventfully, followed by adjuvant chemotherapy.     

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.     

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目的 提高腹膜后肿瘤的手术效果。方法 回顾分析1980－2001年腹膜后肿瘤28例的治疗情况。结果 完整切除21例，部分切除或探查活检7例，无手术死亡。5年生存率分别为：未切除组14．3％，恶性切除组37．5％，良性切除组69．2％。结论 提高手术切除率是改善预后的关键，术前核磁共振（MRI），数字减影（DSA）检查有助于了解肿瘤内及周围血管的走行，用不同方法处理侵及重要血管的腹膜后肿瘤并争取彻底切除，是减少术后复发，提高生存率的重要方法。     

原发性腹膜后肿瘤手术后复发因素分析

目的　探讨原发及复发腹膜后肿瘤手术治疗经验 ,并分析影响肿瘤术后复发的因素。方法　回顾性分析 1983～ 2 0 0 0年原发性腹膜后肿瘤 35 2例 ,并进行术后肿瘤复发的多因素回归分析。结果　手术 30 8例 ,恶性肿瘤 188例 ,良性肿瘤 12 0例。多因素分析显示 :男性、恶性肿瘤、肿瘤残留者、肿瘤与腹主动脉关系密切者易复发 ,脂肪肉瘤、平滑肌肉瘤、血管外皮细胞肉瘤是易复发的病理类型。结论　原发及复发性腹膜后肿瘤多数可行手术治疗 ,通过对影响复发诸因素分析可预测患者的预后。