Validity and interexaminer reliability of a new method to quantify skin neurofibromas of neurofibromatosis 1 using paper frames.

Background: Skin neurofibromas represent one of the main clinical manifestations of neurofibromatosis 1, and their number varies greatly between individuals. Quantifying their number is an important step in the methodology of many clinical studies, but counting neurofibromas one by one in individuals with thousands of tumors is arduous, time-consuming, and subject to intra and interexaminer variability. We aimed to evaluate the efficacy of a new methodology for skin neurofibromas quantification using paper frames.

Methods: The sample comprised 92 individuals with NF1. Paper frames, with a central square measuring 100 cm2, were placed on the back, abdomen and thigh. Images were taken, transferred to a computer and two independent examiners counted the neurofibromas. The average number of neurofibromas/100 cm2 of skin was obtained from the mean of the three values. The differences in the quantity of neurofibromas counted by two examiners were evaluated with Intraclass correlation coefficient (ICC), paired t-test, Bland-Altman and survival-agreement plots. To evaluate the predictive value of the method in obtaining the total number of neurofibromas, 49 participants also had their tumors counted one by one. Reproducibility was assessed with Pearson's correlation coefficients and simple linear regression model.

Results: There was excellent agreement between examiners (ICC range 0.992-0.997) and the total number of skin neurofibromas could be predicted by the adhesive frames technique using a specific formula (P < 0.0001).

Conclusions: In this article we describe a reliable, easy and rapid technique using paper frames to quantify skin neurofibromas that accurately predicts the total number of these tumors in patients with NF1. This method may be a useful tool in clinical practice and clinical research to help achieve an accurate quantitative phenotype of NF1.