The diagnosis of neurofibromatosis-1 in the child under the age of 6 years.

One-hundred sixty children under the age of 6 years presented for diagnostic evaluation regarding neurofibromatosis-1 (NF-1). Using the National Institutes of Health Consensus Conference criteria, 151 (94%) of the children were classified on initial examination: 112 were diagnosed as having NF-1 and 39 were found to be unaffected (all 39 have remained asymptomatic on follow-up). Nine could not be classified (3 have subsequently met minimal diagnostic criteria on follow-up). Clinical manifestations of NF-1 include cafe au lait spots (97%), freckling in the axillary or inguinal region (81%), Lisch nodules (30%), neurofibromas (15%), pseudoarthrosis (6%), and optic nerve gliomas (4%). More than minimal diagnostic criteria were met by 80% of the children who had a positive family history and by 32% of those who did not. Thus, the clinical diagnosis of NF-1 is possible in the child who is under 6 years of age, and the National Institutes of Health criteria are useful and applicable.

Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors.

The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.

The Neurofibromatosis Clinic of the Children's Hospital of Philadelphia.

The Neurofibromatosis Clinic of the Children's Hospital of Philadelphia is a multidisciplinary clinic that provides a setting in which the diagnosis of neurofibromatosis can be made and follow-up of children with neurofibromatosis coordinated. It also offers genetic counseling to affected individuals and families. The Clinic acts as a referral center to the subspecialty disciplines when such specialty services are required. This report outlines the organization and operation of the Children's Hospital of Philadelphia Neurofibromatosis Clinic. It discusses the protocol used to evaluate the pediatric patient with neurofibromatosis and the importance of continuity of care for the patients and families.

Intracranial visual pathway gliomas in children with neurofibromatosis.

The association between neurofibromatosis and visual pathway gliomas is well documented. The introduction of computed tomography and magnetic resonance imaging has heralded a new era in the understanding of visual pathway gliomas. Both of these noninvasive neuroinvestigative techniques have demonstrated extensive abnormalities throughout the visual pathway in children with visual pathway gliomas, especially in those with neurofibromatosis. The clinical significance of these abnormal areas of brain, especially in asymptomatic patients, is unknown. In an attempt to clarify the incidence, natural history, and clinical course of patients with neurofibromatosis and visual pathway lesions, we reviewed our experience with 24 patients managed consecutively at Children's Hospital of Philadelphia over the past 12 years. The patients in this series were compared to 29 children with visual pathway gliomas without neurofibromatosis who were evaluated at our institution over the same period of time. Visual pathway gliomas in children with neurofibromatosis differ from those in children without neurofibromatosis. In general, lesions tended to be more extensive in patients with neurofibromatosis and the clinical course of these patients is more variable. Twelve of the 24 patients with neurofibromatosis in our series had symptoms of progressive disease at the time of diagnosis and underwent treatment with variable results. Twelve children with neurofibromatosis and visual pathway lesions had static lesions at the time of diagnosis and, to date, 3 have developed progressive disease. From our review we can make some recommendations concerning the management of children with neurofibromatosis and visual pathway gliomas, but many questions remain unanswered. Sequential follow-up of a large cohort of both asymptomatic and symptomatic children with neurofibromatosis and visual pathway lesions is needed to more definitively outline the best management approach for these patients.

Childhood neurofibromatosis: risk factors for malignant disease.

Forty-five children with both neurofibromatosis and malignant tumors were compared with a pediatric population with neurofibromatosis without tumors to ascertain if any of the clinical manifestations of this disorder were associated with either tumor development or histology. No such factors emerged except that, in most of the optic glioma patients, the neurofibromatosis mutation was paternally inherited. Concordance of histologic tumor types was seen when malignancies occurred in affected family members, similar to that noted in the literature. Although cancer is independent of the other manifestations of neurofibromatosis and these manifestations may vary among family members, it appears that malignant tumors are often concordant when they occur within a family.

CT of sarcomatous degeneration in neurofibromatosis.

Neurofibromatosis is a relatively common disorder that often involves many organ systems. One of the least understood aspects of this malady is a well documented potential for sarcomatous degeneration of neurofibromas. The inability to identify patients at risk and the lack of noninvasive screening methods for symptomatic patients often leads to late diagnosis. In six of seven subsequently proven neurofibrosarcomas, CT demonstrated low-density areas that histopathologically appeared to be due to necrosis, hemorrhage, and/or cystic degeneration. The density differences within these sarcomas were enhanced by the intravenous administration of iodinated contrast agents.