Cutaneous malignant melanoma and neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well.

Medical management of neurofibromatosis 1: a cross-sectional study of 383 patients.

BACKGROUND: The morbidity and mortality caused by neurofibromatosis 1 are a result of complications that may involve any of the body systems. Two models of management have been proposed for the detection of various complications in specialized neurofibromatosis clinics: investigation protocols (including extensive imaging and analysis of 24-hour urinary catecholamine levels); or clinical follow-up without imaging. OBJECTIVE: Our purpose was to validate the strategy of clinical follow-up (without routine imaging and 24-hour urinary catecholamine levels). METHODS: We retrospectively compared the number of treated complications during 2 successive periods from our database: screening investigations from November 1988 to June 1995 and clinical examination from July 1995 to June 2000. RESULTS: The number of treated complications during the 2 periods was not statistically different (27/166 vs 28/217; Fisher's exact test, P =.39). CONCLUSION: Screening investigations added little to clinical follow-up. Indeed, routine clinical examination can easily identify complications that require treatment in adult patients with neurofibromatosis 1.

Aberrant axon neurofilaments in schwannomas associated with phacomatoses.

Neurofibromas and schwannomas express S100 protein, while axon filaments are not commonly found in schwannomas. Histopathological distinction between neurofibromas and schwannomas is usually easy, except for some variants. To assess the reliability of immunohistochemistry results for the differential diagnosis of the latter, 46 neural tumors of the skin were studied: 31 schwannomas [12 schwannomatosis, 7 neurofibromatosis type 2 (NF2)-associated, 12 solitary] and 15 plexiform neurofibromas associated with neurofibromatosis type 1. All tumors were subjected to immunohistochemical-labeling studies with antibodies to S100 protein and axon-specific neurofilament proteins. All tumors were positive with anti-S100 protein antibody. Schwannomas were strongly and diffusely positive while neurofibromas displayed more varied and limited S100 protein reactivity. Axon filaments were detected in 15 of 15 plexiform neurofibromas and 7 of 19 schwannomas associated with NF2/schwannomatosis. None of the 12 solitary schwannomas reacted with anti-axon neurofilament antibodies. Aberrant axons were observed in the schwannomas associated with NF2/schwannomatosis but not in the solitary schwannomas. Therefore, when there are multiple neural tumors, immunohistochemical visualization of axons may be misleading if it is not related to the clinical context and the standard histological features.

Clinical risk factors for mortality in patients with neurofibromatosis 1: a cohort study of 378 patients.

OBJECTIVE: To identify the main clinical features associated with mortality in patients with neurofibromatosis 1. DESIGN: Cohort study. SETTING: Referral center for neurofibromatosis. PATIENTS: Three hundred seventy-eight patients with neurofibromatosis 1 who had more than 1 year of follow-up in the center. MAIN OUTCOME MEASURES: Mortality. Clinical features, especially dermatological, were evaluated as potential factors associated with mortality. RESULTS: Factors associated independently with mortality were the presence of subcutaneous neurofibromas (odds ratio, 10.8; 95% confidence interval, 2.1-56.7; P<.001), the absence of cutaneous neurofibromas (odds ratio, 5.3; 95% confidence interval, 1.2-25.0; P =.03), and facial asymmetry (odds ratio, 11.4; 95% confidence interval, 2.6-50.2; P<.01). CONCLUSIONS: Some features that can be found by a routine clinical examination are associated with mortality in patients with neurofibromatosis 1. Clinical follow-up should be focused on patients with subcutaneous neurofibromas and/or the absence of cutaneous neurofibromas and/or facial asymmetry.