Assessment and Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1

Purpose of Review: Cutaneous neurofibromas (cNFs) are a hallmark feature of neurofibromatosis type 1 (NF1) and are associated with substantial physical, psychosocial, and quality-of-life burden. Progress in therapeutic development is hindered by the absence of validated, feasible, and responsive tools for quantifying cNFs and assessing their clinical effect and treatment response. This scoping review aimed to identify and summarize existing methods used to measure and quantify cNFs, evaluate their effect on health-related quality of life (HRQoL), and assess outcome measures used in cNF treatment studies. Recent Findings: A comprehensive search of 6 electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform) from inception to April 2025 identified 1,916 records, of which 61 articles met inclusion criteria (48 primary studies and 13 review articles). Eight studies evaluated instruments for cNF measurement, while 5 assessed HRQoL using patient-reported outcomes (PROs). A greater cNF burden, particularly an increased number, size, and facial involvement, was consistently associated with poorer HRQoL. Among identified PROs, the cNF-Skindex was the only tool specifically developed for cNFs. Twenty-three studies investigated therapeutic interventions, and 12 registered clinical trials evaluated medical or surgical treatments. Considerable heterogeneity was observed in outcome selection, with many studies lacking clearly defined end points or relying on nonvalidated or inconsistently applied measures. Summary: This scoping review highlights the availability of several methods to quantify cNFs; however, their clinical feasibility, responsiveness, and interpretability remain limited. Outcome measures used across cNF intervention studies are highly variable, impeding comparison across studies and synthesis of evidence. The cNF-Skindex represents a promising cNF-specific HRQoL instrument but requires further validation, including assessment of responsiveness and minimal important difference thresholds. Standardization of cNF measurement approaches and outcome selection is urgently needed to support robust clinical trials and enable meaningful evaluation of treatment efficacy in NF1.