The role of biopsy in the diagnosis of renal tumors of childhood: Results of the UKCCSG Wilms tumor study 3

BACKGROUND: The United Kingdom Children's Cancer Study Group (UKCCSG) Wilms Tumor Study 3 has adopted preoperative chemotherapy for Wilms tumors (WT), but required prechemotherapy biopsy for histologic diagnosis. The aims of this review were to assess the usefulness and safety of prechemotherapy biopsy and to compare histologic features of WT before and after chemotherapy. PROCEDURE: There were 286 eligible patients but only 241 biopsies and 226 nephrectomy case slides were submitted for panel review. The presence of different histologic components of WT before and after chemo therapy was retrospectively assessed. RESULTS: Among the 241 cases, the biopsy material in 9 (4%) was not diagnostic, in 28 (12%) that were clinically and radiologically consistent with WT, the biopsy revealed tumors other than WT, and in the remaining 204 (85%) WT was confirmed. Of 188 WT suitable cases, blastema was found in 89% of tumors at biopsy, but in only 50% at nephrectomy; the remainder were either completely necrotic (17%) or showed only epithelial and/or stromal elements (33%). Of 182 children who had percutaneous cutting needle biopsy (PCNB), a fall in haemoglobin (20% of cases) and local pain (19%) were the most common complications. One child required emergency nephrectomy due to massive intratumoral bleeding, another had tumor rupture and subsequently died, and a third developed a needle track recurrence 8 months after the biopsy. CONCLUSIONS: A number of renal tumors (12%) can have the correct histologic diagnosis made by PCNB. Preoperative chemo therapy markedly decrease in the number of samples with preserved blastema. The morbidity associated with PCNB is small. Needle biopsy of any renal mass prior to initiation of chemotherapy is recommended.     

Post‐transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic dilemma: Renal biopsy or nephrectomy?

Cheng E, Fustino N, Klesse L, Chinnakotla S, Sanghavi R. Post‐transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic dilemma: Renal biopsy or nephrectomy?
Pediatr Transplantation 2011: 15: E187–E191. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant lymphoproliferative disorder is a life‐threatening neoplasm that can occur after orthotopic liver transplant. We report a 14‐month‐old female status‐post OLT with an atypical presentation of PTLD as a solitary renal mass. At eight‐wk post‐transplant, she presented with elevated transaminases, CMV counts (73 000 copies/mL), and EBV counts (35 000 copies/mL). CT scan revealed a solid heterogeneously enhancing right renal mass measuring 2.6 × 2.4 × 3.3 cm. The radiological diagnosis was Wilms tumor, although PTLD could not be excluded. Complete resection of a Wilms tumor is potentially curative. A needle biopsy would upstage the malignancy and result in radiochemotherapy that is deleterious to a liver graft. The mass was not amenable to partial nephrectomy. A total nephrectomy, given life‐long nephrotoxic immunosuppressants, was an unfavorable option. Thus, needle biopsy was performed. Histology confirmed monoclonal, EBV‐associated PTLD and diffuse large B‐cell lymphoma. Her therapy included immunosuppression reduction, cyclophosphamide, steroids, and anti‐CD20 monoclonal antibody. Concomitantly, she received Cytogam and gancyclovir. Complete remission was achieved three months after chemotherapy. This case illustrates that young age, CMV infection, and EBV infection are strong risk factors for PTLD. With such risk factors present, any mass or lesion in a solid organ transplant patient should be considered PTLD until proven otherwise.     

A rare case of intrarenal teratoma in a 6-month-old male

We report a rare case of an intrarenal teratoma in a 6-month-old male. Following biopsy, he was successfully managed with a primary nephrectomy. This patient presented as would a Wilms tumor. According to SIOP guidelines, the diagnosis of Wilms tumor is made on clinical and imaging information only, prior to neoadjuvant chemotherapy. This patient was investigated, according to UK (CCLG) guidelines, with a biopsy prior to treatment and therefore avoided unnecessary chemotherapy.     

Pretreatment, ultrasound-guided cutting needle biopsies in childhood renal tumors

BACKGROUND: The current International Society of Paediatric Oncology (SIOP)-10 protocol does not allow pretreatment histological classification of low-stage renal tumors in children for fear of needle tract recurrences. The aims of this retrospective study were to evaluate the safety, sensitivity, and specificity of ultrasound-guided cutting needle biopsies (UCNB) performed at our institution in pediatric patients with renal tumors. PROCEDURE: Of 28 pediatric patients presenting with a renal tumor between 1988 and 1996, 25 underwent biopsy with the Biopty biopsy instrument (needle diameter 1.2 mm). The preoperative biopsy and nephrectomy slides were reviewed by a SIOP reference pathologist. The patients' hospital records were reviewed and biopsy complications were noted. RESULTS: At review of the nephrectomy slides, the diagnoses were: Wilms tumor (16 patients), with anaplasia in one case, rhabdoid tumor (2 patients), neuroblastoma (2 patients), mesoblastic nephroma (2 patients), clear cell sarcoma (1 patient), malignant teratoma (1 patient), and renal cell carcinoma (1 patient). No needle tract recurrence or other major complication was observed. The only complication was local pain at the biopsy site, which occurred in 24% (6/25) of the cases. The sensitivity of UCNB was 76% (19/25); five biopsies did not yield diagnostic material and one was not concordant. All cases of Wilms tumor were correctly diagnosed by UCNB, but only 33% (3/9) of the other tumors. CONCLUSIONS: In all cases of Wilms tumor a correct diagnosis was made. The overall sensitivity was 76%. UCNB proved to be a safe procedure that was not associated with needle tract recurrence or other serious complications.     

Tumor de Wilms: revisión de nuestra experiencia en los últimos 15 años

Introduction

Wilms’ tumour is the most frequent renal tumour in children. Multi-modal treatment includes chemotherapy and surgery, with or without radiotherapy. The survival is excellent, with rates exceeding 90%. A review is presented on our experience over the last 15 years of treating Wilms’ tumour in Hospital Niño Jesús, Madrid.

Wilms tumour: prognostic factors,staging, therapy and late effects

Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Société Internationale d’Oncologie Pédiatrique (SIOP) and the Children’s Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial development and participation will improve matching of treatment needs with prognosis, reducing long-term complications in the majority. The advent of molecular markers of disease severity and improved functional imaging might help. This work was supported in part by grants P30 CA-21765.     

Bilateral Wilms’ tumour in a developing country: a descriptive study

Purpose

To present our experience of 20 children with bilateral Wilms’ tumour seen in a resource-challenged environment over a 10-year period.

Method

All patients with a diagnosis of bilateral synchronous Wilms’ tumour were identified and recruited.

Results

Study patients represented 11 % of a cohort of 177 new patients with Wilms’ tumour seen over the same period. Three patients had a syndromic predisposition to Wilms’ tumour. Metastatic disease was seen at presentation in four patients (20 %) and three children presented with unilateral tumour rupture. One patient presented with paraplegia and one with obstruction of the duodenum. All children received neoadjuvant chemotherapy. One HIV-infected child died of IRIS after neoadjuvant treatment, but before surgery. One child died of progressive disease after unilateral nephrectomy. Nephron-sparing surgery was performed in 22 kidneys and 15 kidneys were removed in toto. Following enucleation of tumours, three children had positive margins. Discordant histopathology was seen in 53 % of patients. Overall survival at 2 years is 85 %.

Conclusion

Despite significant co-morbidity and advanced disease, bilateral Wilms’ tumour is a treatable disease in a resource-constrained environment.     

Imaging in unilateral Wilms tumour

Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe, has consequences for the choice of imaging modality at diagnosis. In Europe, the International Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy followed by surgery. Imaging (US, CT and MRI), clinical history and examination will help predict whether the findings are consistent with Wilms tumour. Furthermore, in the UK preoperative image-guided biopsy is advised to help identify the small group of patients who, despite typical imaging features of Wilms tumour, have other types of neoplasia that require alternative management. In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior to chemo- and radiotherapy. Hence imaging must provide detailed anatomical information for surgical planning. This article discusses the role of imaging at diagnosis and the relative strengths and weaknesses of the available radiological techniques. We also focus on imaging the lung for metastatic disease and the consequences (to the patient’s ultimate outcome) of CT-diagnosed small pulmonary nodules and discuss the radiological diagnosis and consequences of tumour rupture present at diagnosis.     

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.     

The efficacy and toxicity of SIOP preoperative chemotherapy in Malawian children with a Wilms tumour

Background

In Malawi, preoperative chemotherapy for Wilms tumour is a logical strategy, but detailed information on toxicity and efficacy in such a resource limited setting has been unavailable.

Procedure

Patients diagnosed with a unilateral Wilms tumour received preoperative chemotherapy—a two‐drug 4‐week regimen for localized disease and 6 weeks of a three‐drug regimen for metastatic disease. Estimated maximum tumour diameter, decrease in tumour size, resectability, stage distribution and haematological toxicity during therapy were documented.

Results

At diagnosis, 28% of 72 patients had an estimated maximum tumour diameter of more than 25 cm; 29% of patients had metastases. Eight children (11%) died during preoperative chemotherapy. More than half (59%) of the patients developed moderate neutropenia (neutrophils <1.0 × 10⁹/L; CTC grade 3) and 27% severe neutropenia (CTC grade 4 neutrophils <0.5 × 10.9/L). Grade 4 neutropenia occurred significantly more frequently in children receiving the three‐drug regimen compared to the two‐drug regimen; 50% (10/20) versus 15% (6/40) (P = 0.004). Fifty‐seven percent of all patients had CTC grade 4 anaemia (Hb < 6.5 g/dL) during treatment. Most tumours (92%, 56/61) showed a response to chemotherapy but 14% (8/58) remained unresectable.

Conclusion

Preoperative chemotherapy for Wilms tumour causes considerable haematological toxicity and treatment‐related mortality in malnourished Malawian children. A significant number of children have unresectable disease despite preoperative chemotherapy. To reduce treatment related mortality, consideration should be given to starting treatment with reduced doses in acutely malnourished patients. Pediatr Blood Cancer 2012;59:636–641. © 2012 Wiley Periodicals, Inc.     

Burkitt's lymphoma presenting with blindness: a case report.

A 10-year-old schoolboy was referred to the Ophthalmic Unit of Ahmadu Bello University Teaching Hospital because of sudden loss of sight following 5 days of severe frontal headache. The child had bilateral ptosis with internal and external ophthalmoplegia and fixed and dilated pupils. There was no papilloedema. Eight days later, a jaw tumour and a rapidly enlarging abdominal tumour appeared. A fine needle aspiration biopsy of the jaw tumour confirmed Burkitt's lymphoma. Combination chemotherapy with cyclophosphamide, vincristine and methotrexate (COM) led to a rapid resolution of the jaw and abdominal tumour but the child never regained his sight. Cerebrospinal fluid examination was not helpful in reaching a diagnosis.     

SIOP PODC: Clinical guidelines for the management of children with Wilms tumour in a low income setting

Wilms tumour is a relatively common and curable paediatric tumour. Known challenges to cure in low income countries are late presentation with advanced disease, malnutrition, failure to complete treatment and limited facilities. In this article, management recommendations are given for a low income setting where only the minimal requirements for treatment with curative intent are available (setting 1). These include general management, supportive care, social support and registration of patients. Recommendations specific for Wilms tumour care include diagnostic procedures with emphasis on the role of ultrasonography, preoperative chemotherapy with a reduced dosage for malnourished children and postoperative chemotherapy based on surgical staging. Pediatr Blood Cancer 2013; 60: 5–11. © 2012 Wiley Periodicals, Inc.     

Aniridie et tumeur de Wilms : deux cas de néphroblastome fœtal rhabdomyomateux

Background.

Wilms tumor is associated in 7 to 10 % of patients with congenital abnormalities. Among those, aniridia is the most constant feature of the WAGR syndrome that includes, in one third of cases, Wilms tumor. We report two cases of aniridia associated with fetal rhabdomyomatous nephroblastoma.

Case reports.

Case 1. A one-year old girl with congenital aniridia was admitted for macroscopic hematuria. Abnormal ultrasonography and tomodensitometry revealed a large, bilateral, kidney tumor. The patient was given actinomycin and vincristine, without efficacy. Bilateral tumorectomy was performed 6 months later and the histological study showed a fetal rhabdomyomatous nephroblastoma. This patient is in remission at the age of 5. Case 2. A boy, also with congenital aniridia, presented with macroscopic hematuria at the age of 2 years revealing a nephroblastoma located on his right kidney. Preoperative chemotherapy remained uneffective and the nephrectomy performed 1 month later permitted the diagnosis of fetal rhabdomyomatous nephrolastoma. The patient is well 4 years later.

Conclusion.

Both cases of fetal rhabdomyomatous nephroblastoma, a histological variant of Wilms tumor, seem to be the first reported in the WAGR syndrome.     

儿童原发性恶性非肾母细胞瘤性肾脏肿瘤诊治特点

目的 探讨儿童原发性恶性非肾母细胞瘤性肾脏肿瘤的临床诊治特点.方法 回顾性分析1993年4月至2008年1月问收治的11例儿童原发性恶性非肾母细胞瘤性肾脏肿瘤患儿的临床资料.根据临床表现及术前影像学检查并于术前行穿刺活检,治疗方法主要为术前介入和/或全身化疗、手术切除、术中热灌注化疗和术后化疗.结果 肾细胞癌6例,无瘤长期(平均32个月)生存率66.7%.中胚性肾瘤3例,均获3年以上无瘤生存.肾透明细胞肉瘤1例,术后复发死亡.肾横纹肌样瘤1例,术后化疗2个月复发,结论儿童原发性恶性非肾母细胞瘤性肾脏肿瘤发病率低,临床表现与肾母细胞瘤相似,术前诊断较为困难,其中肾细胞癌发病年龄多为年长儿,而肾透明细胞肉瘤、中胚层肾瘤和肾横纹肌样瘤则多见于小婴儿.经过多项系统性治疗,中胚层肾瘤预后较佳,肾细胞癌次之.     

Long‐term remission of bilateral Wilms tumors that developed from premature separation of chromatids/mosaic variegated aneuploidy syndrome due to bilateral nephrectomy and peritoneal dialysis

We report a 38‐month‐old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. After right nephrectomy, dactinomycin monotherapy was administered for the left Wilms tumor; however, severe adverse reaction prevented the patient from receiving further chemotherapy. Left nephrectomy was then performed without postoperative chemotherapy. The patient survived for 15 months after bilateral nephrectomy without peritoneal relapse, metastasis of Wilms tumor, or the occurrence of rhabdomyosarcoma and maintained a good quality of life while receiving peritoneal dialysis at home.     

Needle biopsy and preoperative chemotherapy for massive unilateral and bilateral Wilms' tumor

Massive unilateral and bilateral Wilms' tumors present complex therapeutic questions. We report five cases in which we used radiological investigations, needle biopsy, and preoperative chemotherapy followed later by definitive surgery.     

Controversies and advances in the management of Wilms' tumour

Wilms tumour is one of the success stories of paediatric oncology with long term survival approaching 90% in localised disease and over 70% for metastatic disease. Although appearing relatively simple compared to other cancer treatment regimens, successful treatment of Wilms tumour requires meticulous attention to correct staging of the tumour and good communication between the paediatric surgeon, pathologist and oncologist. The controversy of whether pre-operative chemotherapy results in a reduced overall burden of treatment compared to immediate nephrectomy has been addressed by the recently closed UKW3 randomised trial. Challenges remain in identification of histological and molecular risk factors for stratification of treatment intensity to allow safe reduction in therapy and avoidance of late sequelae for the majority while leading to increased biological insights and ultimately novel therapies for the minority of high risk tumours. Genetic predisposition to Wilms tumour is conferred by several genes, some of which cause malformation rather than cancer and may be of low penetrance. The proportion of children with heritable disease is uncertain and there remains a need to collect data on the need for screening in this susceptible population.     

Controversies and advances in the management of Wilms' tumour.

Wilms tumour is one of the success stories of paediatric oncology with long term survival approaching 90% in localised disease and over 70% for metastatic disease. Although appearing relatively simple compared to other cancer treatment regimens, successful treatment of Wilms tumour requires meticulous attention to correct staging of the tumour and good communication between the paediatric surgeon, pathologist and oncologist. The controversy of whether pre-operative chemotherapy results in a reduced overall burden of treatment compared to immediate nephrectomy has been addressed by the recently closed UKW3 randomised trial. Challenges remain in identification of histological and molecular risk factors for stratification of treatment intensity to allow safe reduction in therapy and avoidance of late sequelae for the majority while leading to increased biological insights and ultimately novel therapies for the minority of high risk tumours. Genetic predisposition to Wilms tumour is conferred by several genes, some of which cause malformation rather than cancer and may be of low penetrance. The proportion of children with heritable disease is uncertain and there remains a need to collect data on the need for screening in this susceptible population.     

Renal growth in patients nephrectomized for Wilms tumour as compared to renal agenesis

Compensatory growth in 27 undiseased congenital solitary kidneys and in 31 solitary kidneys in patients with Wilms tumour was monitored in long-term follow-up studies by ultrasound volume biometry. In congenital solitary kidneys hypertrophy was not detectable at the time of birth. Parenchymal mass increase achieved 188% of the volume of a healthy kidney within at least 4 years of life and afterwards paralleled the physiological growth documented in healthy kidney pairs. Disease-free kidneys in Wilms tumour patients all developed a similar 180% volume augmentation within 2–4 years after nephrectomy, irrespective of the chosen mode of radiation and single or tripte chemotherapy. The age of the patient at onset of surgical and concomitant conservative therapy determined slight differences in kinetics but not in degree of compensatory growth.Abbreviations ACD actinomycin-D - VCR vincristin - ADM adriamycin     

Surgical management and outcomes of 12 cases of Wilms tumour with intracardiac extension from a single centre

Purpose

To review demographics, effect of preoperative chemotherapy on tumour thrombus, imaging, operative strategy, and outcomes of 12 patients presenting with intracardiac extension of Wilms tumour thrombus.

Methods

A retrospective audit was undertaken on patients with intracardiac extension of Wilms tumour. Patients were identified from the oncology database and information obtained on clinical presentation, stage, preoperative treatment, surgical procedures and complications, histology, and survival status. Ethics approval was obtained from the University of Cape Town Human Research Ethics Committee.

Results

From 1984 to 2016, 337 children with Wilms tumour were treated. Twelve (3.6%) had intracardiac extension of tumour thrombus, nine into the right atrium, and three into the right ventricle. Ultrasound, computerized tomography, magnetic resonance imaging, and echocardiograms were used to assess thrombus level. Patients were staged as stage III(8) and IV(4). All patients received preoperative chemotherapy. Thrombus retracted from the heart in two cases. One patient died preoperatively. Eleven underwent laparotomy, median sternotomy, and cardiopulmonary bypass (CPB). Four underwent cavectomy. Five required cavoatrial patches. Thrombus extending into the hepatic veins was extracted in five patients. There was one intraoperative complication and one perioperative death. Thrombus histology showed viable tumour in 9 of 11 patients. Three patients died of progressive disease. Seven patients are currently disease free.

Conclusion

A combination of imaging is required to determine thrombus extent, and this facilitates surgical planning. Preoperative chemotherapy may cause thrombus regression, thus avoiding CPB. CPB offers appropriate conditions for safe tumour thrombus excision. Full management in centres with appropriately experienced staff and facilities for CPB is recommended.