Hepatoblastoma (HB) is an embryonic neoplasm representing the most frequent malignant liver tumour in childhood. Its tumourigenesis at the molecular level is still poorly understood, and candidate genes are yet to be identified. According to recent reports describing beta-catenin mutations (BCM) at hot-spot regions involving exon 3 in several types of malignancies including HB, we investigated BCM in 16 HBs classified into different histological types. One tumour had been previously confirmed to harbour adenomatous polyposis coli (APC) mutations that exhibit a similar oncogenic effect to that of BCM. Mutations in both exon 3 and its flanking region of the beta-catenin gene were investigated and determined. Twelve tumours (75%) revealed pathogenic BCM, including 5 with missense mutations at codons 32, 34, or 37 and 7 with interstitial deletions that partially or totally affected exon 3. All 7 deletions were in-frame deletions without frameshift. A single nucleotide change at codon 31 regarded as non-pathogenic polymorphism was detected in the tumour possessing APC mutations. Therefore, a total of 13 tumours (81%) were compromised by an enhanced beta-catenin-mediated transcription pathway. Mutations were observed in every histological type of HB. The very high frequency without correlation to histological type indicates that BCM are crucial events in the tumourigenesis of HB.

Spontaneous perforation of the bile duct (SPBD) is a rare disease in children. Pancreatico-biliary maljunction (PBM) has been postulated to contribute to its etiology. We have treated three children with SPBD over 30 years, two of whom had PBM. There was one boy and two girls aged 10 months to 2 years with symptoms of abdominal distension, vomiting, abdominal pain, jaundice, and acholic stools. The diagnosis of SPBD was made by paracentesis showing biliary ascites, and primary biliary and intra-abdominal drainage was performed in all cases. The site of perforation was at the connection of the common bile duct (CBD) with the cystic duct in all cases. In two cases reflux of contrast into the pancreatic duct was noted, the common channel was long (17 and 12 mm, respectively), and the bile amylase level in the CBD was abnormally high (50,000 and 67,000 IU/l, respectively). In the third patient there was no reflux of contrast into the pancreatic duct and the bile amylase and trypsin levels in the CBD and gallbladder were not measurable. Thus, SPBD in children may not be due solely to PBM, but may involve multiple mechanisms.

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Isolated granulomatous inflammation of the appendix is extremely rare, and its etiology is still unknown. Thus, differentiating between idiopathic granulomatous appendicitis and isolated appendiceal Crohn's disease is difficult. We report a case of idiopathic granulomatous appendicitis with long-term follow-up after surgery. A 26-year-old woman was referred to our hospital for investigation of persistent right lower abdominal pain. Abdominal computed tomography showed a mass, suggesting an inflammatory tumor around the appendix; thus, we suspected subacute appendicitis and performed laparoscopically assisted ileocecal resection. Histological examination of the resected specimen revealed several noncaseous epithelioid granulomas in the wall of the appendix, but no foreign bodies, obstructing lesions, or parasites. Stains for acid-fast bacillus and fungi, and serology for yersinia were all negative. The patient has been followed up for 9 years and remains asymptomatic. This clinical course suggests that her isolated granulomatous appendicitis was idiopathic granulomatous appendicitis unrelated to Crohn's disease.

Pleuropulmonary blastoma (PPB) is rare childhood tumor oniginating from either lung or pleura. Although several cytogenetic changes, such as tisomy 2, trisomy 8, and loss of 17p material, have been reported, evidence of gene mutations is still lacking. Pathologically, PPB shares similarities with rhabdomyosarcoma in which p53 mutations arefrequently detected. Possible implication of p53 mutations in PPB was investigated. PPBs of 3 patients were analyzed for occurrence of p53 mutations by using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method, and the nature of mutations was confirmed by direct sequencing. Two PPBs were confirmed to harbor p53 mutations. One was a Val to Leu substitution at codon 173, and another was a ArgArg to TrpCys substitution at codons 282 and 283. In each tumor, only the mutated allele was detected, suggesting inactivation of p53. Both patients with mutations had fatal outcome, while the remaining patient in whom no mutation was detected is disease free for 3 years after completion of treatment. The results raise the possibility that p53 inactivation can occur as a nonrandom genetic change involving the pathogenesis and outcome of PPB. Further studies in a larger series are necessary to clarify these matters.