Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1

Abstract

Background: To examine the natural growth dynamics of internal plexiform neurofibromas (PNs) in patients with neurofibromatosis 1 (NF1).

Methods: Two hundred and one NF1 patients underwent whole body MRI (WBMRI). Tumour burden was estimated volumetrically. Non-parametric Spearman's rho correlation coefficients were used to analyse the relationship of growth rate to tumour volume and age. Chi-squared and Mann-Whitney U tests were used for analysing the association of tumour occurrence with sex or age. Chi-squared tests were used to analyse the association of tumour growth with age group.

Results: Seventy-one of 171 patients with serial WBMRI exams had internal PNs (median follow up 2.2 years [1.1 to 4.9 years]). Median whole body tumour volume was 86.4 mL [5.2 to 5878.5 mL]) with a median growth rate of 3.7%/year (-13.4 to 111%/year) that correlated with larger whole body tumour volume (P<0.001) and lower age (P=0.004). No new PNs developed in 273.0 patient-years among patients without tumours. Rate of new tumour development among patients with PNs was 0.6%/year (95% confidence interval 0.02 to 3.4%). Twenty-seven (13.5%) tumours increased significantly and were more frequent among children (P<0.001). Growth rate of tumours was inversely correlated with age (Spearman's rho=-0.330, P<0.001). Seventy-one (35.5%) tumours had smaller volumes on follow up (median -3.4%/year [-0.07% to -35.9%/year]).

Conclusion: Children with NF1 and internal PNs are at risk for tumour growth. Most PNs grow slowly or not at all, and some decrease in size. New tumours are infrequent in NF1 patients with PNs and unlikely in patients without PNs.

Figure 1

Whole body tumour volume by person and age; whole body tumour volume by person and age in 71 patients with NF1. Patient 1890, who developed MPNST during the course of the study, is shown in red. Patients 1140, 1730, and 2490, who were treated for MPNSTs prior to their entry into the study, are shown in green.

Figure 2

Development of a new PN on MRI; the only PN that arose during the period of observation in this study is shown in this figure (Patient 1670, Tumour 5). A: cross-sectional image through the thigh at age 46 years; B: cross-sectional image through the thigh at age 48 years.

Figure 3

Tumour volume of individual tumours by age; tumour volume of 201 individual tumours by age in 95 patients with NF1. The MPNST that developed in Patient 1890 during the course of the study is shown in red. The other two tumours that were seen in Patient 1890 are shown in blue, and six tumours that were followed in Patients 1140, 1730 and 2490, who were treated for MPNSTs prior to their entry into the study, are shown in green.