Hepatoblastoma in patients with molecularly proven familial adenomatous polyposis: Clinical characteristics and rationale for surveillance screening

Abstract

Familial adenomatous polyposis (FAP) due to APC mutation is associated with an increased risk of hepatoblastoma. All cases of hepatoblastoma in patients with FAP reported in the literature were reviewed. One hundred and nine patients were identified. Thirty-five patients (of 49 with data) were diagnosed with hepatoblastoma prior to a later diagnosis of FAP (often in association with advanced colorectal carcinoma), emphasizing a need to identify patients earlier with germline APC mutations for early colorectal carcinoma screening. Hepatoblastoma may present at birth, and screening for hepatoblastoma in infancy in families with FAP prior to APC mutation testing results may be warranted.

APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures

“…Compared to sporadic non-APC-HB patients (the SIOPEL series of 76 French patients as well as the series of 15 patients resected in Bicêtre hospital), APC-HB patients showed quite similar clinical and biological features ( Table 2), as it has been reported in a recent retrospective analysis in the US 22 and in the meta-analysis of the literature. 6 In concordance with those studies, APC-HB patients appeared to be slightly older and enriched in the male gender, but none of these features allowed a clinical-based identification of FAP patients. This pleads for a systematic screening for APC mutations in HB patients even in the absence of familial history of tumors, since 25-30% of FAP cases arise from a de novo mutation.…”

“…8 We observed a complete absence of mutations in the classical FAP hotspot at codon 1309 in APC-HB patients (P < .05), a feature also found in the recent meta-analysis of APC-HB spectrum of mutations. 6 Genotype-phenotype correlations have been reported in FAP for a long time, with mutations localized in some regions of the gene being associated with the severity of the polyposis or with some extra-colonic features such as desmoid tumors or congenital hypertrophy of the retinal pigment epithelium. 4 In APC-HB, the exclusion of mutations in the 1309 codon and in the MCR may relate to the need for a fine-tuning of the activation of the Wnt/β-catenin pathway in HB tumorigenesis, as it has been proposed for colorectal adenoma.…”

“…5 Patients with FAP have a 750-7500 fold increase relative risk to develop HB, but the prevalence of HB in APC mutation carriers is below 3%. 6 The need for surveillance for HB development in those children is still a matter of debate. Many large North American centers have recommended such a surveillance 6 whereas in Europe most groups do not recommend surveillance considering the low prevalence of HB in this population 2 and the high cure rates of patients with HB.…”

“…6 The need for surveillance for HB development in those children is still a matter of debate. Many large North American centers have recommended such a surveillance 6 whereas in Europe most groups do not recommend surveillance considering the low prevalence of HB in this population 2 and the high cure rates of patients with HB. Conversely, since FAP is associated with several malignancies (colon, thyroid, brain, bone, soft tissues neoplasms) and can be unknown because of the high proportion of de novo mutations, 4 diagnosing FAP in children with HB is a major issue for the management of the patient and his/her relatives including monitoring colonic adenomas and performing prophylactic surgery before colon adenocarcinoma occurrence in APC mutation carriers.…”

American College of Radiology LI-RADS in pediatric patients: the good, the bad, and the future

“…Most patients are diagnosed within the first 5 years of life [3]. Most cases of hepatoblastoma are sporadic, though several associations have been reported [4][5][6]. Second, up to 70% of pediatric HCCthe second most common primary pediatric liver tumordevelops in children without underlying liver disease during the latter part of the first or early second decade [7,8].…”