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Paediatric Oncology approach (nephroblastoma): the International Society of The pathology of Wilms' tumour

In the International Society of Paediatric Oncology renal tumour trials, preoperative chemotherapy has been successfully applied with resulting reduction of tumour rupture and increased favourable stage distribution of nephroblastoma. Postoperative treatment includes chemotherapy and sometimes radiotherapy in a riskadapted approach based on histological sub-classification and stage of the tumour. However, preoperative chemotherapy alters the tumour’s histological features and distribution of subtypes, and makes staging more difficult. The paper highlights the most common practical diagnostic difficulties that a pathologist is faced with in dealing with pretreated nephroblastomas. It emphasises the importance of a systematic, step-by-step analysis based on adequately sampled material, in order to accurately sub-classify a nephroblastoma as a low, intermediate or high risk tumour and assign its genuine stage. Finally, it outlines the standard operating procedure for submission of renal tumours for rapid central pathology review which allows the treating oncologists to apply the optimal treatment protocol. Renal tumours comprise 7e8% of all tumours in the first 15 years of life. Wilms’ tumour (WT) or nephroblastoma is by far the most common (w85% of cases), followed by renal cell carcinomas (w3e5%), mesoblastic nephroma (w3%), clear cell sarcoma of the kidney (w3e4%), rhabdoid tumour of the kidney (w2%) andmiscellaneous rare tumours (w2%). Accurate histological diagnosis and staging of these tumours are critical because their treatment and prognosis are very different. Since they are rare, they still represent a diagnostic and therapeutic challenge, and it is important to treat and study them through large national and international multicentre collaborative trials which include centralised pathological review in order to verify the diagnosis and stage of cases entered on the trials. The first multicentre trial started in 1969 in the United States through the National Wilms’ Tumour Study group (NWTS; now part of the Children’s Oncology Group, COG) with the most important objective being the establishment of optimal treatment for WT. NWTS/COG have been treating WTs with surgery first, followed by, if necessary, postoperative chemotherapy and radiotherapy. On the other hand, preoperative therapy has been an essential part of the International Society of Paediatric Oncology (SIOP) treatment strategy since its first trials. In the first two trials (SIOP 1, 1971e74; and SIOP 2, 1974e76) preoperative radiotherapy was used. Since the third trial (SIOP 5, 1977e79) it has been replaced with preoperative chemotherapy which has shown very similar results in terms of preventing tumour rupture(s) and inducing more favourable stage distribution, with more stage I tumours requiring less postoperative therapy (SIOP 5, 1977e79; SIOP 6, 1980e86; SIOP 9, 1987e93; and SIOP 93 01, 1993e2001). Due to the different therapeutic approaches between the two groups, there are further differences in histological subclassification and staging (see below), making a direct comparison of their results complicated. In 1978, Beckwith and Palmer introduced a histological classification of primarily operated WTs with two main groupsdanaplastic and nonanaplasticdwhich became a basis for their treatment in NWTS/COG trials. By studying the correlation between the histological features and survival of WTs that received preoperative chemotherapy from the early SIOP trials, it became apparent that they could be sub-classified into three treatment groups: favourable, standard and unfavourable histology groups. In the more recent classifications (SIOP 93 01 and the current SIOP 2001), they have been renamed into low risk, intermediate risk and high risk tumours (table 1). 8 This concept of stratification of tumours into low, intermediate and high risk groups has later been followed in other tumours of childhood, including rhabdomysarcomas, neuroblastomas, hepatoblastomas and germ cell tumours. Further analyses of WT subtypes from SIOP trials have resulted in removal from or addition of certain subtypes to the risk groups. So, for example, WT with fibroadenoma-like structures, which was earlier regarded as a favourable histology tumour, has disappeared from the new classification since it has been recognised that it represented a pattern of growth of some WTs rather than a distinct histological type. On the other hand, it has been shown that a tumour ’s response to preoperative chemotherapy is an indicator of good prognosis, so completely necrotic WT has been placed in the low risk tumour group (table 1). In the current SIOP 2001 trial (2001e), other WT types including epithelial, stromal and regressive (sub)type with >90% necrosis are being investigated since preliminary results have indicated that their prognosis is better than for other WT types from the intermediate risk group. 12 In the same way, the presence of a certain amount of blastema after preoperative chemotherapy clearly indicates its nonDepartment of Histopathology, School of Medicine, Cardiff University, Cardiff, UK Childhood Cancer Research Unit, Astrid Lindgren’s Children’s Hospital, Karolinska Institutet, Stockholm, Sweden Correspondence to Professor G M Vujani c, Department of Histopathology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; vujanic@cf. ac.uk Accepted 3 August 2009 Published Online First 16 August 2009 102 J Clin Pathol 2010;63:102e109. doi:10.1136/jcp.2009.064600 Review group.bmj.com on February 12, 2010 Published by jcp.bmj.com Downloaded from