Thoracic neural crest tumors in Beckwith–Wiedemann syndrome

Abstract

differentiation and histologic type of the ependymoma, age at diagnosis, degree of surgical resection or prior treatment and subsequent development of extraneural metastases was found [4]. The exact route of extraneural metastases is not known, but in the vast majority metastases occurred in the wake of craniotomy, suggesting iatrogenic vascular seeding [3]. Typically, extraneural metastases of ependymoma occur in the lungs, pleura, and lymph nodes while metastases to the mediastinum, liver, bone, and diaphragmatic muscle are even less common [4]. In most cases, the existence of pleuropulmonary metastases was disclosed only at autopsy usually coexisting with CNS recurrence and systemic metastases [5]. Extraneural metastases or relapses of ependymoma are extremely rare but physicians caring for ependymoma patients must remain aware of this possible complication. Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with increased birth weight, macroglossia, omphalocele, neonatal hypoglycemia, craniofacialanomalies, and visceromegaly [1,2]. The syndrome is a complex genetic disorder caused by dysregulation of multiple growth regulatory genes within the 11p15 region. It is a cancer predisposition syndrome, and at least 7.5% of patients develop a malignant disease; most commonly Wilms tumor [3]. Other embryonal tumors have been reported including hepatoblastoma and rhabdomyosarcoma, but neural crest tumors are rare. We, therefore, add to the literature two children with BWS in whom thoracic ganglioneuroma and ganglioneuroblastoma were found.The first child was diagnosed with BWS complicated by neonatal hypoglycemia, mild macroglossia, omphalocele and cleft palate. She did not have hemihypertrophy. At age 4 years, she underwent a cleft palate repair under general anesthesia when decreased air movement on the left side of her chest was noted. A chest radiograph revealed a large posterior mediastinal mass. Computed tomography (CT) of the chest, abdomen and pelvis showed a left-sided 5.3 cm  4.6 cm  7.4 cm posterior paraspinal mass with speckled calcification that proved to be 123 meta-iodobenzylguanidine (MIBG) avid. There was no evidence of bone marrow involvement. A twenty-four hour urine collection showed an elevated vanillylmandelic acid (VMA) of 9.7 mg/total volume (tv) (normal 0-4) and an elevated homovanillic acid (HVA) of 23.5 mg/tv (normal 0-10). Ferritin was 22.5 ng/ml (normal 10-55). The mass was completely excised, and ganglioneuroma was confirmed on histologic examination of the surgical specimen. No adjunctive radio- Fig. 3. Pulmonary metastasis, consisting of anaplastic cells, immunohistochemically strongly positive for glial acidic fibrillary protein (GFAP, Â600).

Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants

“…Very few patients with BWSp had developed neural crest tumours, with most of them located in the thorax and encompassing neuroblastomas, ganglioneuroblastomas and ganglioneuromas [ 9 , 39 , 40 , 41 ]. To our knowledge, thoracic ganglioneuromas have been reported in only two patients, both 4-year-old girls at the time of the diagnosis [ 39 , 41 ]. Unfortunately, the BWSp molecular group of these two patients was not reported.…”

Genomic Imprinting and Cancer: From Primordial Germ Cells to Somatic Cells

“…Children with BWS have been reported to have a 7.5-9% overall risk for developing embryonal tumours within the first 5-8 years of age (reviewed [3,62,63,79]). The most common tumours include Wilms' tumour and hepatoblastoma, but others including rhabdomyosarcoma, adrenocortical carcinoma, and neuroblastoma have been reported [60,80,81,82,83,84].…”