Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1

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  • 1 Surgical Neurology Branch,
  • 6 Electromyography Section, and
  • 7 Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke;
  • 3 Pediatric Oncology Branch and
  • 4 Neuro-Oncology Branch, Center for Cancer Research, and
  • 5 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and
  • 2 College of Medicine, Northeast Ohio Medical University, Rootstown, Ohio
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OBJECTIVE

Patients with neurofibromatosis type 1 (NF1) are predisposed to visceral neurofibromas, some of which can progress to premalignant atypical neurofibromas (ANFs) and malignant peripheral nerve sheath tumors (MPNSTs). Though subtotal resection of ANF may prevent malignant transformation and thus deaths with no neural complications, local recurrences require reoperation. The aim of this study was to assess the surgical morbidity associated with marginal resection of targeted ANF nodules identified via preoperative serial volumetric MRI and 18F-FDG-PET imaging.

METHODS

The authors analyzed clinical outcomes of 16 NF resections of 21 tumors in 11 NF1 patients treated at the NIH Clinical Center between 2008 and 2018. Preoperative volumetric growth rates and 18F-FDG-PET SUVMax (maximum standardized uptake value within the tumor) of the target lesions and any electromyographic or nerve conduction velocity abnormalities of the parent nerves were measured and assessed in tandem with postoperative complications, histopathological classification of the resected tumors, and surgical margins through Dunnett’s multiple comparisons test and t-test. The surgical approach for safe marginal resection of ANF was also described.

RESULTS

Eleven consecutive NF1 patients (4 male, 7 female; median age 18.5 years) underwent 16 surgical procedures for marginal resections of 21 tumors. Preoperatively, 13 of the 14 (93%) sets of serial MRI studies and 10 of the 11 (91%) 18F-FDG-PET scans showed rapid growth (≥ 20% increase in volume per year) and avidity (SUVMax ≥ 3.5) of the identified tumor, respectively (median tumor size 48.7 cm3; median growth rate 92% per year; median SUVMax 6.45). Most surgeries (n = 14, 88%) resulted in no persistent postoperative parent nerve–related complications, and to date, none of the resected tumors have recurred. The median length of postoperative follow-up has been 2.45 years (range 0.00–10.39 years). Histopathological analysis confirmed significantly greater SUVMax among the ANFs (6.51 ± 0.83, p = 0.0042) and low-grade MPNSTs (13.8, p = 0.0001) than in benign neurofibromas (1.9).

CONCLUSIONS

This report evaluates the utility of serial imaging (MRI and 18F-FDG-PET SUVMax) to successfully detect ANF and demonstrates that safe, fascicle-sparing gross-total, extracapsular resection of ANF is possible with the use of intraoperative nerve stimulation and microdissection of nerve fascicles.

ABBREVIATIONS ANF = atypical neurofibroma (neurofibroma with nuclear atypia); ANNUBP = atypical neurofibromatous neoplasm of uncertain biological potential; EMG = electromyographic; hgMPNST = high-grade MPNST; lgMPNST = low-grade MPNST; MPNST = malignant peripheral nerve sheath tumor; NCI = National Cancer Institute; NCV = nerve conduction velocity; NF1 = neurofibromatosis type 1; NIH = National Institutes of Health; SUVMax = maximum SUV within the tumor.

Supplementary Materials

    • pdf Supplementary Figure and Tables (PDF 318 KB)

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Contributor Notes

Correspondence Prashant Chittiboina: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. prashant.chittiboina@nih.gov.

INCLUDE WHEN CITING Published online October 25, 2019; DOI: 10.3171/2019.7.JNS191353.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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