Head and Neck Plexiform Neurofibroma

• Involvement of Cranial Nerve Ganglion as an Independent Risk Factor for Malignant Transformation of Head and Neck Plexiform Neurofibromas in Neurofibromatosis Type 1
• Plexiform Schwannoma of the Foot: A Case Report
• Plexiform Neurofibroma Versus Parotid Tumour - A Challenge in Management
• Pediatric Spindle Cell Tumor in Head and Neck Region: A Case Series
• Facial Diffuse Plexiform Neurofibroma-associated Mandibular Deformities: Surgical Interventions and Monitoring of Treatment Results in a Patient for Over 40 Years
• Selumetinib for symptomatic, inoperable plexiform neurofibromas in pediatric patients with neurofibromatosis type 1: the first single-center real-world case series in Japan
• A single-center case study series assessing the effect of selumetinib use in patients with neurofibromatosis-related plexiform neurofibromas
• Clinical experiences in precision treatment of giant plexiform neurofibromas of head, face, and neck

Plexiform neurofibromas, in the head and neck region, pose unique clinical and surgical challenges due to their proximity to vital neurovascular structures and potential for disfigurement and functional impairment.

• Occurs in ~30–50% of patients with NF1.
• Typically appears in childhood or adolescence.
• Head and neck PNFs represent a high-risk anatomical subtype due to morbidity and potential for malignant transformation.

• Visible mass with possible facial asymmetry or disfigurement.
• Pain, paresthesias, or motor deficits depending on nerve involvement.
• Airway obstruction, dysphagia, or dysphonia if deep cervical or cranial nerves are involved.
• Often infiltrative, non-encapsulated, and progressive.
• May extend along cranial nerves, brachial plexus, or into the skull base.

• Risk of malignant peripheral nerve sheath tumor (MPNST) is estimated at 8–13% in NF1 patients with PNF.
• Recent evidence suggests cranial nerve ganglion involvement is an independent risk factor for transformation.

→ See: Gu Y, et al. *Plast Reconstr Surg*. 2025 Jul 8. DOI: 10.1097/PRS.0000000000012302.

• Surgical resection remains the mainstay but is often incomplete due to infiltration and risk of neurovascular injury.
• Debulking for functional or cosmetic purposes.
• Emerging therapies:
  • Selumetinib (MEK inhibitor) approved for symptomatic, inoperable PNFs in children with NF1.
• Close monitoring with serial MRI and neurological evaluation.

• Highly variable depending on size, location, and resectability.
• Significant psychosocial impact due to facial disfigurement.
• Lifelong surveillance required due to growth potential and risk of malignant transformation.

In a retrospective cohort analysis of patients undergoing surgical resection of head and neck plexiform neurofibromas (PNF) at a tertiary neuro‑oncology center. Gu et al. from the Shanghai Ninth People’s Hospital, Shanghai (Departments of Plastic & Reconstructive Surgery, Pathology, Neurosurgery) published in the Plastic and Reconstructive Surgery Journal to identify risk factors—particularly cranial nerve ganglion involvement—predicting malignant peripheral nerve sheath tumor (MPNST) transformation in head and neck PNF among NF1 patients.

Main conclusions: - Four percent (19/470) of clinically treated head & neck PNF became malignant. - Independent risk factor: involvement of cranial nerve ganglia (adjusted OR 3.10; 95% CI 1.07–9.00). - Ganglion–involved PNF transformed faster (HR 7.20; 95% CI 2.33–22.28), accelerating time to MPNST by ~36% ¹⁾

*✅ Strengths:* - Large, single‑center cohort with surgery-confirmed diagnoses over 11 years (2012–2023). - Robust statistical methods (logistic + Cox regression) identify both risk magnitude and temporal acceleration. - Clinically actionable endpoint: close surveillance and earlier intervention for ganglion‑involved PNF.

*⚠️ Limitations:* - Retrospective design; possible selection bias—only surgically treated cases included. - PNF heterogeneity in size, volume, and precise anatomical pathways may influence results but lacked standardized imaging metrics. - External validity limited: single‑center data from China; demographic & management differences may apply elsewhere.

*🧠 Methodology critique:* - Appropriate use of multivariable logistic regression; however, only a few covariates tested. Other confounders (e.g., NF1 genotype, prior radiotherapy, growth rate) omitted. - Cox model hazard ratio (7.20) is large but CI wide—suggests smaller sample or variable follow-up times.

*🎯 Clinical takeaway for neurosurgeons:* Evaluate head and neck PNF for cranial nerve ganglion involvement via imaging (MRI/CT); if present, patients should undergo intensified monitoring (e.g., 6‑month imaging) and early biopsy or resection upon suspicious changes.

Final verdict: 7 / 10 A solid observational study that highlights a radiographically discernible risk factor with clinical implications. Would benefit from prospective validation and inclusion of additional predictive variables.

Bottom line: Cranial nerve ganglion involvement in head & neck PNF triples malignant transformation risk and accelerates progression—this marker should prompt more aggressive monitoring and management.

Category:

1. Neurofibromatosis Type 1
2. Peripheral Nerve Tumors
3. Malignant Peripheral Nerve Sheath Tumor

Tags: neurofibromatosis type 1, plexiform neurofibroma, MPNST, risk factor, cranial nerve ganglion, retrospective cohort

Corresponding author email: wangzichao@sjtu.edu.cn