Long-Term Follow-up of von Recklinghausen Neurofibromatosis

Abstract

To document the natural history of von Recklinghausen neurofibromatosis, we followed up a nationwide cohort of 212 affected patients and families identified in Denmark 42 years ago. We obtained follow-up information on 99 percent. Because all 76 probands were identified through hospitals, they may include a disproportionate number of severe cases of neurofibromatosis. To diminish this effect of selection bias, we distinguished between the probands and their affected relatives. In a comparison with the general population, survival rates were significantly impaired in relatives with neurofibromatosis, worse in probands, and worst in female probands. Malignant neoplasms or benign central nervous system tumors occurred in 45 percent of the probands, giving a relative risk of 4.0 (95 percent confidence limits, 2.8 to 5.6) as compared with expected numbers. Multiple primary neoplasms were found in 15 probands, but only 1 relative. Compared with the general population, male relatives with neurofibromatosis had the same rate of neoplasms, whereas female relatives had a nearly twofold higher rate (relative risk, 1.9; 1.1 to 3.1). Nervous system tumors were disproportionately represented. We conclude that patients with severe neurofibromatosis requiring hospitalization often have a poor prognosis, but incidentally diagnosed relatives may have a considerably better outcome.

Orthopaedic Case of the Month: A 14-Year-Old Boy With a Medial Thigh Soft Tissue Mass

“…Approximately 1 . 2 of patients with malignant peripheral nerve sheath tumors have neurofibromatosis, Type I (NF-1) [16,17,27,46,51]; however, the cumulative risk of having malignant peripheral nerve sheath tumors develop among patients with NF-1 varies from 2% to 29% [17,34,47]. On immunohistochemistry, S-100 positivity frequently is seen [13,34].…”

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

“…In the longitudinal study by Sorensen et al (1986), 212 patients with NF1 were followed up over a period of 40 years, and 57 malignant tumours were found in this population. Although many of these tumours were those seen commonly in the general population, there was a greatly increased rate of CNS tumours in the study group, particularly gliomas.…”

“…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.…”

Neurofibromatosis: part 2 – clinical management

“…Some cohort studies have reported a mean reduction of 8 to 15 years 4,5 while studies based on death certificates have shown a greater reduction (of about 16 to 20 years) 6,7 in life expectancy. The leading reported cause of early death in all age groups is malignant neoplasm, especially malignant peripheral nerve sheath tumor (MPNST).…”