Neonatal hepatoblastoma in a newborn with severe phenotype of Beckwith–Wiedemann syndrome

Abstract

Beckwith-Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alpha-fetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith-Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the diagnosis of an extremely aggressive hepatoblastoma. The latter was successfully treated with pre-surgical reductive chemotherapy, gross total mass resection, and subsequent chemotherapy. Based on this observation, the tumor surveillance routinely suggested every 3 months should be more intense and with closer time intervals in newborns with severe BWS phenotype. We suggest monitoring neonatal αFP every 20 days in such cases.

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

“…4 Cost-effectiveness of ultrasound screening is proven; 43 we hypothesize that patients with IC1-GoM may benefit from an intensification of abdominal ultrasound during the first Phenotypes in Beckwith-Wiedemann syndrome A Mussa et al 3 years of life, as most of Wilms' tumors are diagnosed before that age and appears justified by their 25% chance of developing a Wilms' tumor, the well-proven beneficial effect of early diagnosis, and the low invasivity of abdominal ultrasound. 44 Conversely, the dosage of the tumor marker serum alpha-fetoprotein as a screening method for the early diagnosis of hepatoblastoma is debated, given the complexity of its interpretation in childhood, 45,46 the low incidence of hepatoblastoma and the invasivity of frequent blood drawns, which is commonly responsible for the lack of adherence to screening protocols. 47 We believe that monitoring is worthwhile at least in UPD patients, given their high risk of hepatoblastoma.…”

α-Fetoprotein assay on dried blood spot for hepatoblastoma screening in children with overgrowth-cancer predisposition syndromes

“…Therefore, the differences between plasmatic and DBS values we observed likely have little impact since αFP initially decreases with an approximate 10-fold magnitude every month in the first semester. Even taking into account the largest variation we observed in our series between the gold standard and the DBS method, none of the cases of hepatoblastoma in BWS/HH documented in literature (17,19) would have been missed employing the DBS method.…”

“…The current hepatoblastoma surveillance program in these syndromes relies on a 2-3 mo plasmatic αFP determination which is an acceptable schedule to allow early diagnosis of hepatoblastoma. Presumably, some of these rapidly growing neoplasms will be detected earlier with closer αFP measurements, especially in the subset of patients with genetic or phenotypic characteristics associated with very high risk for tumor development (17,19,20). As observed in adults, screening for hepatocarcinoma cirrhotic patients by serum αFP measurement resulted in increased survival rates (34).…”

“…Evidence suggests that BWS/HH patients would benefit from even closer αFP measurements because hepatoblastoma usually grows rapidly (17). This issue is particularly relevant in a subset of high-risk patients (19,20) such as those with severe phenotypes, HH, and organ enlargement (2,3,(21)(22)(23). However, the psychological burden of the closely repeated blood draws can reduce the compliance and complicate the follow-up (6).…”

Screening Hepatoblastoma in Beckwith-Wiedemann Syndrome

“…By the way, all the 14 reported cases diagnosed by screening display clearly elevated aFP levels at diagnosis once reliable reference values were used. 5 On the basis of these premises, we could debate whether screening all BWS patients for hepatoblastoma is worthwhile, but, in our opinion, screening the UPD ones is mandatory. Collaborative studies are needed to verify proficiency and costeffectiveness of aFP screening in this setting: meanwhile, the application of hepatoblastoma surveillance protocol is prudential and reasonable.…”