Chemotherapy-Induced Histologic Changes in Wilms' Tumors

The nephrectomy specimens of 21 patients with Wilms' tumor who received preoperative chemotherapy consisting of vincristine and actinomycin D, alone or in combination, were studied pathologically; 1 patient also received radiation therapy. Pathological material from 20 randomly selected patients with Wilms' tumor who did not receive preoperative chemotherapy was reviewed and used as a control. Twenty tumors were of favorable histology, and one was unfavorable; all control tumors were of favorable histology. The histological changes were diffuse. The most marked changes occurred in the undifferentiated stroma of 18 tumors: the stroma was edematous; had a fibrovascular background, granulation tissue, and histiocytes; and lacked atypical cells. The blastematous nodules were reduced in size and necrotic or undergoing necrosis in 5 cases. Differentiated elements, including glomeruloid, tubular, and rhabdomyoblastic components, were unaffected. Vascular changes, consisting of fibrinoid necrosis, thrombosis, and acute inflammation were prominent in 15 instances. Two tumors of favorable histology, including one that was a rhabdomyomatous Wilms' tumor, and the tumor of unfavorable histology were unchanged by the therapy. In contrast, the histological changes present in only 4 of the control group, while similar, were rather minimal and focal. This evaluation helps to define the susceptibility of the different elements in Wilms' tumor to chemotherapy.     

Chemotherapy-induced histologic changes in Wilms' tumors

The nephrectomy specimens of 21 patients with Wilms' tumor who received preoperative chemotherapy consisting of vincristine and actinomycin D, alone or in combination, were studied pathologically; 1 patient also received radiation therapy. Pathological material from 20 randomly selected patients with Wilms' tumor who did not receive preoperative chemotherapy was reviewed and used as a control. Twenty tumors were of favorable histology, and one was unfavorable; all control tumors were of favorable histology. The histological changes were diffuse. The most marked changes occurred in the undifferentiated stroma of 18 tumors: the stroma was edematous; had a fibrovascular background, granulation tissue, and histiocytes; and lacked atypical cells. The blastematous nodules were reduced in size and necrotic or undergoing necrosis in 5 cases. Differentiated elements, including glomeruloid, tubular, and rhabdomyoblastic components, were unaffected. Vascular changes, consisting of fibrinoid necrosis, thrombosis, and acute inflammation were prominent in 15 instances. Two tumors of favorable histology, including one that was a rhabdomyomatous Wilms' tumor, and the tumor of unfavorable histology were unchanged by the therapy. In contrast, the histological changes present in only 4 of the control group, while similar, were rather minimal and focal. This evaluation helps to define the susceptibility of the different elements in Wilms' tumor to chemotherapy.     

胎儿横纹肌瘤型肾母细胞瘤

目的 探讨胎儿横纹肌瘤型肾母细胞瘤（ＦＲＮ）特点和恰当的治疗方法。方法 从１９５５～１９９６年３６９例肾母细胞瘤中检出ＦＲＮ１０例。回顾性分析其临床表现、病理组织学特点和预后。结果 １０例ＦＲＮ均因腹部肿大或腹部肿物入院。经术前放、化疗肿瘤不缩小。６例单侧病变做瘤肾切除,５例获随访均长期存活。４例双侧病变中１例做双侧单纯肿瘤切除,３例做一侧瘤肾切除,对侧肾部分切除或单纯肿瘤切除,随访存活２年。结论     

Chest radiography versus chest CT in the evaluation for pulmonary metastases in patients with Wilms' tumor: a retrospective review

BACKGROUND: Determination of the presence of pulmonary metastases in children with Wilms' tumor is an important part of staging and treatment. We sought to compare the efficacy of chest radiography (CXR) and chest CT in the evaluation for pulmonary metastases in patients with Wilms' tumor. MATERIALS AND METHODS: This retrospective study included 83 children with Wilms' tumor diagnosed between 1980 and 1993. All patients with pulmonary nodules (n = 12) as well as 14 Wilms' tumor patients without pulmonary metastases (control group) had blinded review of the CXR and chest CTs by three pediatric radiologists. Presence, size, and certainty of metastatic diagnosis were recorded. Medical records were reviewed. The remaining 57 patients had review of their medical and imaging records to confirm the absence of pulmonary metastases. RESULTS: Ten of the 12 with pulmonary masses had imaging available for review. Eight had both positive CXR and chest CT examinations. Two patients had pulmonary nodules seen by CT only: one had a right cardiophrenic angle mass and died as a result of liver metastases. The other had a solitary nodule, which proved to be a plasma-cell granuloma. Overall, the CXR and chest CT data concur in 79/81 (98%). CONCLUSION: CXR alone appears adequate for the diagnosis or exclusion of pulmonary metastases in patients with Wilms' tumor.     

Pulmonary metastases in children: an analysis of surgical spectrum.

Pulmonary surgery is frequently used for the treatment of metastasis or nodules in children with various types of malignancies. However, the indications and effectiveness of pulmonary metastatectomy have not been evaluated recently. Therefore, a retrospective study was conducted to analyse the results of pulmonary metastatectomy in children. Children who underwent pulmonary metastatectomy at our department between 1990 and 2000 were reviewed. Eighteen children consisting of 11 boys and 7 girls (age range, 3 to 18 years) underwent thoracotomy for pulmonary metastasis excision. The primaries were osteosarcoma (n = 2), synovial sarcoma (n = 1), fibrosarcoma (n = 1), Ewing's sarcoma (n = 2), mesenchymal chondrosarcoma (n = 1), Wilms' tumour (n = 4), clear-cell sarcoma (n = 1), Hodgkin lymphoma (n = 3), hepatoblastoma (n = 1), hepatocellular carcinoma (n = 1) and haemangioendotheliosarcoma (n = 1). Pulmonary metastases were encountered either at the time of initial diagnosis (22 %) or occurred within 6 months to 5 years. They were frequently nodular (94 %), unilateral (94 %) and located in the right lung (70 %). The number of metastases were frequently one (56 %) or two (28 %). Excision was done by means of wedge resection (88 %), segmentectomy (6 %), and lobectomy + wedge resection (6 %). The nodules contained tumour cells in most cases (n = 14) (78 %), mature nephrogenic elements (6 %) and no tumour tissue (16 %) in the remaining cases. Histology was similar to that of the original tumour in 12 cases. However, synovial sarcoma was encountered in metastasis in one case with fibrosarcoma primary. Re-thoracotomy was performed in 22 % of cases for the recurrent lesion, which in only one case was a true local recurrence. Overall disease-free survival rate was 56 % during the follow-up period (mean, 36.4 +/- 31.8 months). Pulmonary metastatectomy may increase survival in carefully selected children, though it is unlikely to cure the patient. Therefore combined therapies such as chemotherapy and/or radiotherapy should be continued in the postoperative period.     

Cyst formation and cavitation in pulmonary metastases from Wilms' tumor A report of two cases

Two children with pulmonary metastases from Wilms' tumor are presented. In one case the lesions evolved into large cysts and in the other case cavitation occurred within two metastatic nodules. These are extremely rare complications of metastases from Wilms' tumor. The possible mechanisms are briefly discussed.     

畸胎瘤样肾母细胞瘤治疗体会及文献回顾

目的 探讨儿童畸胎瘤样肾母细胞瘤临床诊断和治疗方法,提高临床对该病的认识.方法 回顾我院2007年至2016年间诊治的4例儿童畸胎瘤样肾母细胞瘤,男2例,女2例,年龄2～40个月,平均年龄21个月;原发灶:右肾3例,左肾1例;根据COG分期为Ⅰ、Ⅱ、Ⅲ、Ⅳ期(肺及骨髓)各1例,分析其临床表现、诊断及治疗方法.结果 4例患儿均行肾脏肿瘤根治性切除术,其中Ⅲ、Ⅳ期患儿术前行化疗再行根治术;3例术后辅以化疗,术后复发1例(化疗不敏感);3例早中期患儿预后可(2例随访时间超9年,1例随访3年),1例Ⅳ患儿再次手术后化疗加放疗中.结论 儿童畸胎瘤样肾母细胞瘤是肾母细胞瘤的罕见病理类型,临床症状通常难与经典肾母细胞瘤鉴别,主要依靠术前影像学及病理诊断,患侧肾脏肿瘤根治性切除术为主要治疗手段,早中期TWT患儿预后良好,至于保肾肿瘤切除术在该类型肾母细胞瘤的应用,暂未见文献报道,本组病例数较少,也未涉及.对于晚期TWT患儿,可能因为其独特的病理特征,其预后可能比经典肾母细胞瘤更差.     

Maturation of Wilms' tumor pulmonary metastases to benign fibromas after therapy

A 3-year-old girl with Wilms' tumor developed pulmonary metastases 5 months after diagnosis. All but one of the visible lesions disappeared after thoracic irradiation and multiple-agent chemotherapy. Subsequent thoracotomy revealed 17 small nodules in addition to the visible lesion, and all of them proved to be fibromas. It would appear that the Wilms' tumor metastases to the lung were made to mature to benign neoplastic processes after the treatments given.     

Ultrasound differential diagnosis of kidney tumors in childhood

Between 1979 and 1989 21 renal tumors (8 girls and 13 boys) were diagnosed and treated in the Pediatric Hospital of the University of Erlangen. Additionally, there was evidence of nephroblastomatosis in 5 children with Beckwith-Wiedemann Syndrome and hemihypertrophy. One of these infants developed a Wilms' tumor at the age of 3 1/2 years. The most frequent tumor was the Wilms' tumor, which was diagnosed in 14 children. Wilms' tumor are sonographically well delineated, round or oval tumors which often enclose small cysts (72%) but rarely calcifications (5%) and show inhomogenous liver like echogenicity. Metastasis in liver, spleen or abdomen occurred in 2 infants. The most frequent renal tumor in neonates was the mesoblastic nephroma (3 infants). All mesoblastic nephromas were well delineated round tumors with inhomogenous echo-texture and equal or increased echogenicity in comparison to the liver. They often enclosed small cysts but no metastasis or calcifications. Angiomyolipomas of the kidneys could be diagnosed in two children with tuberous sclerosis. These tumors were echogenic nodules spread all over the kidney. We found multilocular nephroblastomas with multiple irregularly delineated cysts in one child. In an other child multiple renal lymphomas simulating solid tumors with liver-like echogenicity could be found.     

Complete remission of a highly malignant, progressive under therapy Wilm's tumor using the combination carboplatin and etoposide (VP 16)]

A Wilms' tumor in a 4 year old girl did not diminish under preoperative chemotherapy following SIOP 9/GPO study guidelines. Surgery revealed an anaplastic (high grade) nephroblastoma infiltrating pancreas, transverse colon, and diaphragm. During postoperative treatment with ifosfamide, vincristine, actinomycin D, and doxorubicin, there was massive tumor growth per continuitatem in chest and abdomen within 6 weeks. Following a French study for relapsed Wilms' tumor, we gave 160 mg/m2 carboplatin and 100 mg/m2 etoposide on 5 consecutive days. After only one cycle, the tumor showed already remarkable regress. We applied six cycles of carboplatin/etoposide and a abdominal radiation. At the end of therapy, the patient was in complete remission. Side effects of chemotherapy were severe bone marrow aplasia and a moderate and reversible decrease of creatinine clearance. The combination of carboplatin and etoposide is a promising therapy in Wilms' tumor resistant to classic nephroblastoma drugs like vincristine, doxorubicin, and actinomycin D.     

Prognostic significance of metastatic site at diagnosis in Wilms' tumor: results from a single center

The purpose of this study was to identify the prognostic significance of pulmonary and liver involvements present at diagnosis in children with Wilms' tumor. From 1971 to 2002, 57 patients with stage IV Wilms' tumor were diagnosed, treated, and followed in the authors' institution. Metastases were detected by chest radiography, abdominal ultrasonography, and/or thoracoabdominal computed tomography. Nephrectomy with tumor resection was performed and appropriate chemotherapy was given to all the patients. The Kaplan-Meier survival method was used to calculate survival. The log-rank test was used to compare the groups with respect to survival. The age range was 1.25 to 15 years (median 4 years). Thirty-seven patients had only lung metastases, 12 had only liver metastases, 6 had both lung and liver metastases, 1 had adrenal gland metastases, and 1 had other site metastases. The overall survival rate in the whole group was 37.1%. The overall survival rates for lung and liver metastases were 50.2% and 16.6%, respectively. The overall survival rates were significantly different between the two groups (P = 0.005). Only one patient survived in the group with liver involvement. Liver involvement at diagnosis indicates a worse prognosis than lung involvement. Wilms' tumor patients with liver metastases should be treated with more intensive regimens than those with lung metastases.     

TGFBR1和FGF9蛋白参与miRNA-140-5p调控肾母细胞瘤细胞的增殖过程

目的 本研究拟探讨rniRNA-140-5p在肾母细胞瘤增殖过程中的调控作用以及TGF-BR1和FGF9蛋白参与此过程的作用机制.方法 采用miRNA芯片技术分析肾母细胞瘤患儿肿瘤组织和瘤旁正常组织的miRNA表达谱,结合生物信息学预测和文献报道,选取表达差异显著的miR-NA-140-5p作为研究对象,扩大样本进行Real-time PCR验证;MTS方法检测miRNA-140-5p对细胞增殖率的影响;双荧光素酶实验验证miRNA-140-5p的直接下游靶基因;Western-blot法检测TGF-BR1蛋白表达;ELISA法检测细胞上清中FGF9蛋白表达.结果发现与瘤旁组织相比,miRNA-140-5p在肾母细胞瘤组织和瘤旁正常组织的相对表达量分别为1.69±0.83和6.37±3.25,肾母细胞瘤组miRNA-140-5p的表达量明显降低(P＜0.05).在肾母细胞瘤细胞株G401及SK-NEP-1中,发现过表达miRNA-140-5p可有效降低G401及SK-NEP-1的增殖率,将miRNA无关序列(miRNA-con)转染组细胞增殖率设为100％,与其相比,转染miRNA-140-5p的G401细胞组的增殖率为(87±15)％比(100±20)％,SK-NEP-1细胞组为(91±12)％比(100±9)％,组间比较,差异均有统计学意义(P值均＜0.05).利用生物信息学软件对miRNA-140-5p直接下游靶基因进行预测,结合肾母细胞瘤相关基因,选择TGFBR1和FGF9基因为miRNA-140-5p的直接下游靶基因;通过双荧光素酶实验证实miRNA-140-5p可直接靶向TGFBR1和FGF9基因.将miRNA-con转染组TGFBR1蛋白表达量设为1,与其相比,过表达miRNA-140-5p的G401及SK-NEP-1细胞内,TGFBR1蛋白表达量降低(G401细胞降为0.67;SK-NEP-1细胞降为0.87)(P＜0.05).与miRNA-con转染对照组相比,G401及SK-NEP-1细胞上清中FGF9蛋白表达量下降,G401组为(478.66±66.32) pg/ml比(535.64±78.53) pg/ml,SK-NEP-1细胞组为(486.57±71.01)pg/ml比(601.26±77.68) pg/ml,组间比较,差异均有统计学意义(P值均＜0.05).结论 患儿肾母细胞瘤中miRNA-140-5p表达量低于瘤旁正常组织,miRNA-140-5p影响肾母细胞瘤细胞的增殖,TGFBR1和FGF9蛋白可能参与了miRNA-140-5p调控肾母细胞瘤细胞增殖的过程.     

Renal cell carcinoma in children

Renal cell carcinoma is a rare tumor in childhood, however, rare tumors must be kept in mind if tumor therapy protocols like the SIOP-9 or SIOP 93-01 Wilms' tumor trial include preoperative chemotherapy based on clinical and radiologic findings without further histologic tumor confirmation. We present a 12-year-old boy initially believed to have a stage IV Wilms' tumor with pulmonary metastasis. Following chemotherapy with doxorubicin, vincristine, and actinomycin D, subsequent tumor nephrectomy revealed a highly differentiated renal cell carcinoma (pT₂pN₀). Wedge resection of the lung showed no evidence of a pulmonary metastasis (M₀). The benefit of preoperative chemotherapy with regard to downstaging of the tumor must be considered carefully, taking into account the risk of incorrect tumor diagnosis.     

Congenital Generalized Myofibromatosis: A Disseminated Angiocentric Myofibromatosis

Infantile myofibromatosis occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications. We report the findings in two male infants with fatal congenital generalized myofibromatosis (CGMF) who presented with multiple dermal and subcutaneous nodules at birth. Imaging studies revealed bony and visceral lesions, which progressed despite chemotherapy. One infant had severe hypercalcemia associated with extensive lytic bone lesions. Both infants died in respiratory failure and had a combination of pulmonary CGMF and diffuse alveolar damage. Involvement of skin, soft tissue, bone, heart, lungs, liver, gastrointestinal tract, and endocrine organs was confirmed at autopsy in each case. A consistent histologic pattern of interlacing fascicles of myofibroblasts with abundant eosinophilic cytoplasm was noted, with variable necrosis and calcifications in some sites. The myofibroblasts displayed vimentin and smooth muscle actin immunoreactivity. The lungs in each case had the presumably early lesions of CGMF with an angiocentric and perivascular growth of myofibroblasts. A similar vascular pattern was present in all affected organs. These two cases demonstrate the extraordinary presentation of CGMF, which suggests its multifocal origin from vascular subintimal mesenchymal or smooth muscle cells whose phenotype is that of myofibroblasts.     

Unique Dermal and Subcutaneous Botryoid Rhabdomyosarcoma Associated with Mature Renal Tissue: Is this an Extrarenal Wilms' Tumor?

A unique dermal and subcutaneous botryoid rhabdomyosarcoma admixed with ectopic mature renal tissue, overlying the left lateral lumbosacral region of a 4-1/2-year-old girl is reported. The tumor was devoid of blastemal or immature epithelial elements and nephrogenic rests. The relationship of this lesion to an extrarenal Wilms' tumor with exclusive myogenous differentiation is discussed.     

儿童未成熟畸胎瘤与成熟畸胎瘤中神经上皮组织的生物学特点分析

目的 对儿童未成熟畸胎瘤和成熟畸胎瘤内决定肿瘤分化程度的神经上皮组织进行多项免疫组化指标检测,分析肿瘤细胞的生物学特性.方法 收集儿童畸胎瘤病理组织标本55例,根据病理诊断分为成熟畸胎瘤和未成熟畸胎瘤二组,提取肿瘤内神经上皮组织标本分别进行能反映肿瘤细胞增殖、凋亡、侵袭力和神经胶质细胞成熟度的Bax、Bcl-2、PCNA、Ki-67、CyclinE、p14ARF/p16β、MMP-9和GFAP各指标分别进行免疫组化染色.结果 未成熟畸胎瘤中的神经上皮组织CyclinE呈低表达,成熟畸胎瘤也呈低度表达;p14AW/p16β两组均为较高表达;PCNA在未成熟畸胎瘤呈较高表达,在成熟畸胎瘤中较低表达;Ki-67在未成熟畸胎瘤呈较低表达,在成熟畸胎瘤中表达程度较前者更低;Bcl-2在未成熟畸胎瘤呈中度表达,而在成熟畸胎瘤中为较低表达;Bax在二组均呈中度表达;MMP-9在二组均为较低表达;而GFAP在未成熟畸胎瘤为低表达,而在成熟畸胎瘤中则为高表达.结论 儿童未成熟畸胎瘤中分化程度较低的神经上皮组织具有一定的增殖、分化、侵袭转移能力,但在良恶性指标方面仍接近成熟畸胎瘤的分子生物学特点,偏向良性或交界性肿瘤.GFAP可能是成熟与未成熟畸胎瘤的一种有效的鉴别指标.     

肾母细胞瘤微卫星DNA变化分析

目的 研究分析１３例肾母细胞瘤（Ｗｉｌｍｓ肿瘤）患儿５个染色体点微卫星标记的变化。方法 ５个微卫星标记分别为：Ｄ７Ｓ１８０８、Ｄ９Ｓ１６１、Ｄ１２Ｓ１０５６、Ｄ１７Ｓ７９１和Ｓ２２Ｓ２７４,应用ＰＣＲ方法扩增Ｗｉｌｍｓ肿瘤组织ＤＮＡ,以该患儿正常组织作对照,扩增产物用含脲素的聚丙烯酰胺凝胶电泳及银染技术进行分析。结果 １３例Ｗｉｌｍｓ肿瘤患儿检测５条染色体５个位点的微卫星多态标记,只１例患儿７号染     

Metastatic Intracranial Chordoma in a Child with Massive Pulmonary Tumor Emboli

A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.     

Pilot Study of Cardiac Function After Treatment of Childhood Wilms' Tumor with Doxorubicin

To assess the cardiotoxicity of moderate doses of anthracyclines and to control for possible contributions of other drugs, cardiac function in 12 patients 1 year 11 months to 9 years 4 months off treatment for Wilms' tumor whose therapy had included vincristine, dactinomycin, and the anthracycline doxorubicin (270 to 300 mg/m² cumulative dose) was compared with that of 9 patients (controls) whose therapy had included vincristine and dactinomycin but no doxorubicin. The small numbers of patients studied suggest that at a median of 6 years off therapy only small numbers of patients will have cardiac function values below age-related normal values. To confirm these results and to determine whether abnormalities are progressive or are clinically important, large cohorts of patients such as those available to the National Wilms' Tumor Study need to be studied.     

Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function.

To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71% of predicted value in group 1, 58% in group 2, and 94% in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated.