Surgical Treatment and Complications of Deep-Seated Nodular Plexiform Neurofibromas Associated with Neurofibromatosis Type 1

Ikuta, Kazunari; Nishida, Yoshihiro; Sakai, Takeharu; Koike, Hiroshi; Ito, Kan; Urakawa, Hiroshi; Imagama, Shiro

doi:10.3390/jcm11195695

Cited by 4 publications

(2 citation statements)

References 33 publications

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“…Until recently, surgery was one of the only treatments available for NF1-PN and NF1-PN-related complications; it is still considered the only potentially curative treatment option [1,5,30,32]. Its use and extent need to be tailored to the size of the PN, its location, growth rate, and radiologic features, and the overall general health and well-being of the patient [1,30,35]. Indications for surgery include neurologic compromise or impact on vital structures, pain, and disfigurement, with the overall aim of surgery to reduce morbidity and improve QoL [1,30].…”

Section: Surgerymentioning

confidence: 99%

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

et al. 2023

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Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.

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Section: Surgerymentioning

confidence: 99%

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

et al. 2023

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“…Diagnostically, however, differentiating between PN, AN, and MPNST remains clinically challenging as a result of insensitive clinical exams 10,11 , overlapping findings on imaging 12 , and tissue heterogeneity leading to sampling biases on tissue biopsy 13 . Biopsy also carries with it the risk of peripheral nerve injury 14,15 , further complicating the diagnostic workup. This is unfortunate as the therapeutic management of these entities is quite different, given their varying levels of malignant potential.…”

Section: Introductionmentioning

confidence: 99%

Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics

Sundby,

Szymanski,

Pan

et al. 2024

Preprint

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Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 121 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.

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A rare clinical manifestation of plexiform neurofibroma in the absence of neurofibromatosis-1: a case report

Rwomurushaka,

Mremi,

Hussein

et al. 2024

International Journal of Surgery: Global Health

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Plexiform neurofibroma is a benign tumor of peripheral nerves that occurs in up to 30% of patients with neurofibromatosis type-1 (NF-1). We present a case of a 15-year-old male patient without NF-1, with an 11-year history of a slow growing, painless mass on the left side of the back extending to the gluteal region, with no constitutional symptoms but with some scoliosis. Histology of the mass was compatible with a plexiform neurofibroma. Plexiform neurofibromas commonly occur in, but are not limited to the craniofacial region. The mainstay of treatment is surgical resection, but complete resectability is challenging due to their locally infiltrative growth pattern. This highlights the need for patient-specific management strategies, even when established guidelines are in place.

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Surgical Treatment and Complications of Deep-Seated Nodular Plexiform Neurofibromas Associated with Neurofibromatosis Type 1

Cited by 4 publications

References 33 publications

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics

A rare clinical manifestation of plexiform neurofibroma in the absence of neurofibromatosis-1: a case report

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