Neurofibromatosis type 1 and malignancy in childhood

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non-neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5-33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft-tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low-grade gliomas, 3 high-grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non-Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high-grade brain tumors also occur. Thus, careful and regular follow-up is crucial for early detection of malignancy in NF1 patients.

Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1

“…The association of other embryonic tumours and NF1 is also under debate. Varan et al (75) report two neuroblastoma cases in their cohort of NF1 patients. It is important to keep in mind that also neuroblastoma (86) and Wilms' tumour (81,82) have been diagnosed in CMMRD patients.…”

“…NF1-associated pilocytic astrocytomas and OPG have a particularly benign behaviour and hardly ever develop into life-threatening disease (10,68,69). There are, however, also a few case reports (70-72) and retrospective clinical-pathological studies (73)(74)(75) that report a possible association of childhood high-grade (WHO III or IV) CNS tumours and NF1. Huttner et al (73) searched for patients who had a childhood glioblastoma and fulfilled NIH clinical criteria of NF1 using a computerized search engine of the medical records of patients from a single institution and found five patients fulfilling these criteria.…”

Metachronous Medulloblastoma in a Child With Successfully Treated Neuroblastoma: Case Report and Novel Findings of DNA Sequencing

“…Analyses of 9,432 long-term neuroblastoma survivors in 3 major studies indicated that 96 patients developed second cancers, including carcinomas, soft tissue sarcomas, glioblastomas, meningioma, melanomas, and hematologic malignancies, but none developed medulloblastoma (Table 3). [5][6][7] Neuroblastoma and, less commonly, medulloblastoma, have been reported in patients with cancer predisposition syn- [22][23][24] Our patient did not have clinical stigmata of these conditions and her genetic testing was negative for these syndromes.…”

An Exceptional Case of Intraparotid Plexiform Neurofibroma Originating from Autonomic Fibers of the Auriculotemporal Nerve

“…Early diagnosis of NF-1 in the pediatric population is crucial, since there is an association between von Recklinghausen disease and malignant tumors such as gliomas, leukemias, melanomas, and non-Hodgkin lymphomas [15]. Additionally, when associated with NF-1, PNs have the potential of undergoing malignant sarcomatous transformation, adding considerably to overall morbidity and mortality [15]. Thus, excluding malignancy of an aggressively growing plexiform lesion, the NF-1 diagnosis additionally justified immediate resection.…”