Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

Imaging plays a key role in the assessment of paediatric renal tumours, especially where the initial treatment approach is to proceed to standardised chemotherapy without histological confirmation. In Europe according to the SIOP guidelines, core needle biopsy is not routinely performed unless the child is older than 10 years. Between 6 months and 9 years, the child is treated with a standard regimen of pre-operative chemotherapy unless there concerns for non-Wilms tumour pathology. Atypical imaging findings may therefore stratify a child into a different treatment protocol and may prompt the need for pre-treatment histology. This review details the latest protocols and techniques used in the assessment of paediatric renal tumours. Important imaging findings are considered especially those features which might prompt the need for a pre-treatment biopsy. Local radiology practices vary, both MRI and CT are widely used as a routine imaging test for the assessment of paediatric renal tumours in Europe. Advances in imaging technology and MRI sequences are facilitating the development of new techniques which may increase the utility of imaging in terms of predicting tumour histology and clinical behaviour. Several of these techniques are considered here. Key points 1. Routine core needle biopsy of a renal mass is no longer recommended by UK and European guidelines for children between 6 months and 10 years with typical clinical and radiological features of a Wilms tumour 2. Ultrasound should be the first imaging modality for investigation of any suspected abdominal mass in a child 3. MRI or CT can be used interchangeably for the assessment of a known renal mass. MRI is recommended in the latest UMBRELLA research trial. 4. It is important to know the imaging features of a renal mass which suggest a non-Wilms tumour 5. Imaging cannot yet differentiate different tumour types or Wilms tumour stage but there are interesting areas of imaging research which may advance this area of imaging in the future

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Objectives: To investigate the extent to which observer variability of computed tomography (CT) lung nodule assessment may affect clinical treatment stratification in Wilms tumour (WT) patients, according to the recent Société Internationale d'Oncologie Pédiatrique Renal Tumour Study Group (SIOP-RTSG) UMBRELLA protocol. Methods: I: CT thoraces of children with WT submitted for central review were used to estimate size distribution of lung metastases. II: Scans were selected for blinded review by five radiologists to determine intra-and inter-observer variability. They assessed identical scans on two occasions 6 months apart. III: Monte Carlo simulation (MCMC) was used to predict the clinical impact of observer variation when applying the UMBRELLA protocol size criteria.Results: Lung nodules were found in 84 out of 360 (23%) children with WT. For 21 identified lung nodules, inter-observer limits of agreement (LOA) for the five readers were ±2.4 and ±1.4 mm (AP diameter), ±1.9 and ±1.8 mm (TS diameter) and ±2.0 and ±2.4 mm (LS diameter) at assessments 1 and 2. Intra-observer LOA across the three dimensions were ±1.5, ±2.2, ±3.5, ±3.1 and ±2.6 mm (readers 1-5). MCMC demonstrated that 17% of the patients with a 'true' nodule size of ≥3 mm will be scored as <3 mm, and 21% of the patients with a 'true' nodule size of <3 mm will be scored as being ≥3 mm. Conclusion:A significant intra-inter observer variation was found when measuring lung nodules on CT for patients with WT. This may have significant implications on treatment stratification, and thereby outcome, when applying a threshold of ≥3 mm for a lung nodule to dictate metastatic status.