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Editor,—The recent article by Giardielloet al (Gut 1996; 39: 867–9) reported eight patients with hepatoblastoma collected from the Johns Hopkins Polyposis Registry. As the authors acknowledge, hepatoblastoma is very rare in patients with familial adenomatous polyposis (FAP). Only 33 cases (24 men, nine women) have been reported in the literature since the first description in 1982.1 ,2 In particular, the exact site of the APC gene mutation has been detected in only a minority of these patients.
Here, we report an additional patient with FAP associated hepatoblastoma, who was discovered during intensive screening of a consecutive series of FAP kindreds.3-6 The patient, a young girl, underwent liver resection for hepatoblastoma when two years old. She survived hepatic resection and is still alive and in good health. She is now 10 years old and has not developed overt colonic polyposis but has congenital hypertrophy of the retinal pigment epithelium (CHRPE). The patient belongs to an extended kindred (23 patients in four generations). There were seven affected patients in the last two generations. Five of them have already undergone colectomy for colonic polyps.3 Interestingly, three patients, all women, also had asymptomatic papillary thyroid carcinoma. Early detection of thyroid tumours was facilitated by the study protocol, which included systematic screening of the thyroid gland by ultrasound. Two of the three resected thyroid specimens also had activation of ret/PTC, a chimeric gene that is restricted to the papillary histotype (ret/PTC1 isoform).5 All affected patients of the present kindred have CHRPE,5 none have desmoid tumours, and all have a 5 base pair deletion ACAAA (position 3183–3187) in exon 15 of the APC gene (codon 1061).6
Interestingly, this same mutation has also been reported in Giardielloet al’s series. This supports the view that patients with hepato- blastoma have APC mutations which tend to cluster in a particular genomic area, restricted to codons 141 to 1387. In our kindred there was one patient with hepatoblastoma and three with thyroid carcinoma.6 All of them also had CHRPE, but not desmoid tumours. These observations suggest that hepatoblastoma and thyroid carcinoma frequently co-segregate with CHRPE, but less frequently with desmoid tumours, which are particularly prevalent in patients with APC mutations beyond codon 1444.7
Intensive screening of FAP kindreds for all known extracolonic manifestations facilitates early detection and improves prognosis. Systematic ultrasound examination of the abdomen should be performed in young siblings of patients with FAP who have an enlarged liver on physical examination. Further characterisation of the spectrum of APC mutations in FAP families with hepatoblastoma as well as characterisation of APC gene function in the liver8 will be the goal of future research.
The study has been supported in part by the National Research Institute (CNR) (grant nos 93.00239.CT04, 94.02376.CT04, 95.00897.CT04); Regione Toscana (grant no 358/C, 1995); and MURST 40% - MURST 60%.
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