Management of plexiform neurofibromas in neurofibromatosis type 1: An Italian Delphi consensus

Abstract

Plexiform neurofibromas (PNs) are among the most complex and challenging manifestations of neurofibromatosis type 1 (NF1). Recent advances in understanding their epidemiology, natural history, biology, and imaging features, together with the introduction of MEK inhibitors, have significantly reshaped clinical management. Despite availability of international recommendations for tumor surveillance in NF1, several aspects of PN management remain incompletely defined in clinical practice. A multidisciplinary panel of 17 Italian NF1 experts conducted a Real-Time Delphi consensus process including a literature review, thematic analysis, and development of consensus statements. Key domains encompassed diagnosis, imaging assessment, surveillance, surgical evaluation, multidisciplinary management, and treatment of PNs. Two rounds of voting were conducted through a dedicated online platform, ensuring anonymity, real-time feedback, and iterative refinement of the statements. Consensus was achieved on 49 final statements. Key recommendations emphasized the importance of early identification of PNs, assessment of internal tumor burden through whole-body MRI, standardized imaging acquisition and reporting, timely recognition and characterization of distinct nodular lesions, and implementation of risk-adapted surveillance strategies. The panel also underscored the importance of patient education regarding signs suggestive of malignant transformation, and recommended a structured multidisciplinary approach to clinical decision-making. Agreement was additionally reached on practical aspects including radiological follow-up, criteria for surgical referral, definitions of PN-related symptoms, inoperability, and integration of surgical and targeted treatment strategies. This national consensus provides an evidence-informed and clinically oriented framework for management of NF1-associated PNs. Complementing existing international recommendations, it offers practical guidance in areas where evidence remains limited. Early diagnosis of Plexiform Neurofibromas (PNs) in patients with Neurofibromatosis type 1 (NF1) is essential to optimize surveillance and therapeutic decision-making. Whole-body MRI at transition to adulthood is useful for assessing internal tumor burden and guiding risk-adapted management strategies. Distinct nodular lesions should be accurately reported in MRI reports and require dedicated multidisciplinary assessment and follow-up. Patient education is a fundamental component of PN management and supports early recognition of disease progression. Multidisciplinary team evaluation is essential for the management of complex, symptomatic or potentially symptomatic PNs. Surgery and MEK inhibitors should be considered complementary therapeutic strategies within a multidisciplinary framework. This national multidisciplinary consensus provides practical recommendations to support clinical decision-making in NF1-associated PNs. Early diagnosis of Plexiform Neurofibromas (PNs) in patients with Neurofibromatosis type 1 (NF1) is essential to optimize surveillance and therapeutic decision-making. Whole-body MRI at transition to adulthood is useful for assessing internal tumor burden and guiding risk-adapted management strategies. Distinct nodular lesions should be accurately reported in MRI reports and require dedicated multidisciplinary assessment and follow-up. Patient education is a fundamental component of PN management and supports early recognition of disease progression. Multidisciplinary team evaluation is essential for the management of complex, symptomatic or potentially symptomatic PNs. Surgery and MEK inhibitors should be considered complementary therapeutic strategies within a multidisciplinary framework. This national multidisciplinary consensus provides practical recommendations to support clinical decision-making in NF1-associated PNs.