Jacques Zeller

Schwannomatosis: A Clinical Entity Distinct from Neurofibromatosis Type 2

BACKGROUND Schwannomatosis includes multiple cutaneous schwannomas, central nervous system tumors and various neurologic deficits. OBJECTIVE To specify the clinical presentation of schwannomatosis, excluding neurofibromatosis type 2 (NF2). METHODS Patients with at least 2 cutaneous schwannomas were evaluated for NF2 criteria. RESULTS 5 men and 2 women (mean age 54 +/- 18 years) we included. Two cases were familial. Cutaneous schwannomas were tender nodules with onset above the age of 30 years. Four patients had paresthesias. Four patients had hypacusis, but auditory brainstem responses showed no retrocochlear involvement. No vestibular schwannoma or central nervous system tumor was found with magnetic resonance imaging in 6 patients. Spinal imaging performed in 6 patients was normal in 5 and showed a spinal schwannoma in the 6th patient. CONCLUSION We strictly eliminated the diagnosis of NF2 in our patients. Exclusion of NF2 in suspected schwannomatosis is essential for further molecular genetic studies.

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; Fishers 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.

Age at diagnosis of neurofibromatosis 1: an audit of practice.

Neurofibromatosis 1 (NF1) is a common genetic disease with an incidence of about 1 in 2,500, an autosomal dominant mode of inheritance and a high rate of new mutations. Two striking aspects of NF1 are its progression with age and its extreme variability. Its diagnosis is based on 7 criteria of which 2 are required for diagnosis: significant cafe-au-lait macules (CLM), neurofibromas of any type or 1 plexiform neurofibroma, freckling in the axillary or inguinal regions, optic glioma, Lisch nodules, a distinctive osseous lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudarthrosis, a first-degree relative with NF1. Although specificity and sensitivity of these criteria are high during adulthood, their sensitivity is low during early childhood: 97% of NF1 patients meet them by the age of 8 years, but only 70% by the age of 1 year. In France, the diagnosis is often made in young adults, and the detection of the early complications needs precocious diagnosis . We conducted a retrospective audit of practice to identify features associated with early diagnosis.