Neurofibromatosis type 1 and childhood cancer

Abstract

Background. Patients with neurofibromatosis type 1 (NF1) are prone to develop malignancy, particularly malignant schwannoma and glioma in adults. Methods. To assess the risk for childhood malignancy in NF1, 26,084 patients with cancer younger than 15 years of age registered from 1969 to 1989 in the Japan Children's Cancer Registry were reviewed. The incidence of NF1 in each type of cancer was compared with that in the Japanese population. Results. Fifty‐six children with cancer had NF1 in the national registry. The incidence of NF1 (0.21%) was 6.45 times that of the expected estimated rate of 1 per 3000 in the Japanese population. These tumors tended to be type and site specific. The NF1 incidence was extremely high in optical nerve glioma (12.5%), other central nervous system gliomas (0.9%), and malignant schwannoma (31.4%). For nonneural tumors, NF1 incidence was increased in rhabdomyosarcoma (1.36%), particularly those in urogenital organs, and in myelogenous leukemia (0.27%). Epithelial carcinomas were not observed in the group of patients with NF1. Conclusion. The risk for glioma and malignant schwannoma increases in children and adults with NF1. Moreover, the risk for two childhood malignancies, myelogenous leukemia and rhabdomyosarcoma, increases in children with NF1. The NF1 gene seems to increase the risk not only for neural tumors but also for some non‐neural tumors in an age‐specific, organ‐dependent pattern of carcinogenesis.

Neurofibromatosis and childhood leukaemia

“…This study confirmed the results of the first population-based study on the incidence of various malignant disorders in neurofibromatosis type 1 (NF-1) (Matsui et al, 1993). The importance of population-based studies of rare diseases cannot be overemphasised.…”

A prospective study of neurofibromatosis type 1 cancer incidence in the UK

“…This has been carried out previously by Matsui et al (1993) and Baptiste et al (1989). Although both these studies verified the increased risk of cancer in NF1, there are problems with this type of study in terms of ascertainment bias.…”

“…Previous data have indicated overall additional malignancy risks in NF1 of between 5 and 15% (Sorensen et al, 1986;Huson et al, 1988;Baptiste et al, 1989;Matsui et al, 1993;Stiller et al, 1994;Friedman and Birch, 1997;Zoller et al, 1997;Evans et al, 2002), and these figures are commonly used when counselling patients; therefore, a more specific risk based on a larger study population would be useful. In addition, the advent of surveillance techniques for early detection and subsequent treatment of malignancy suggested that a more detailed analysis of the question of malignancy risk in NF1 was needed.…”

Pathophysiology of Neurofibromatosis Type 1

“…Matsui et al [22] reviewed data from 26,084 Japanese children with cancer and found 56 with NF1, 6.45 times the expected number. Tumor types in the NF1-affected children included optic glioma, other CNS glioma, MPNST, rhabdomyosarcoma, and leukemia.…”

“…Rhabdomyosarcoma [22] and pheochromocytoma [67] are seen with disproportionately high frequency in individuals with NF1. For other tumors, however, the data are less clear, either because the tumors are rare even in those with NF1, or because the tumors are also common in the general population.…”