World Health Organization Classification of Tumours Pathology and ...

Table 1.10Frequency of paediatric renal malignancies.NeoplasmEstimated relativefrequency (%)Nephroblastoma 80(nonanaplastic)Nephroblastoma 5(anaplastic)Mesoblastic nephroma 5Clear cell sarcoma 4Rhabdoid tumour 2Miscellaneous 4NeuroblastomaPeripheral neuroectodermaltumourSynovial sarcomaRenal carcinomaAngiomyolipomaLymphomaOther rare neoplasmsWT1 allele {2043}. While WT1 alterationsare strongly linked to the development ofnephroblastoma in syndromic cases,their role in sporadic nephroblastoma islimited, with only one third of all nephroblastomasshowing deletion at this locusand only 10% harbouring WT1 mutations.Beckwith-Wiedemann syndrome (characterizedby hemihypertrophy,macroglossia, omphalocele, and visceromegaly)has been localized to chromosome11p15, and designated WT2although a specific gene has not beenidentified {747,1493,2077}. Attempts todetermine the precise genetic event atthis locus has revealed the presence of acluster of imprinted genes; whether ornot a single gene is responsible for theincreased risk for nephroblastomaremains unclear {577}. The preferentialloss of the maternal allele at this locus incases of sporadic nephroblastoma suggeststhat genomic imprinting is involvedin the pathogenesis of some tumours{2000}. Additional genetic loci are associatedwith familial nephroblastoma inpatients with normal WT1 and WT2 {967,1140,1141,1142,2134}. Approximately 1percent of patients with nephroblastomahave a positive family history for thesame neoplasm. Most pedigrees suggestautosomal dominant transmission with variablepenetrance and expressivity.Prognosis and predictive factorsMost nephroblastomas are of low stage,have a favourable histology, and areassociated with an excellent prognosis.A favourable outcome can be expectedeven among most neoplasms with smallfoci of anaplasia. The most significantunfavourable factors are high stage,and the presence of anaplasia. Themajority of blastemal tumours areexquisitely sensitive to therapy.However, tumours that demonstrateextensive blastemal cells following therapyare associated with poor responseto therapy and reduced survival {197,259}. In SIOP protocols, these blastemalchemoresistant tumours are classifiedas "high risk" and are treated likeanaplastic tumours.52 Tumours of the kidney