Cranial nerve and intramedullary spinal malignant peripheral nerve sheath tumor associated with neurofibromatosis-1
- Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada,
- Department of Pathology, Alberta Health Services, University of Calgary, Calgary, Alberta, USA.
- Department of Neurosurgery, Oakland University William Beaumont School of Medicine, Rochester, USA.
- Michigan Head and Spine Institute, Southfield, Michigan, USA.
Michael D. Staudt, Department of Neurosurgery, Oakland University William Beaumont School of Medicine, Rochester, MI, United States.
DOI:10.25259/SNI_595_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Christopher Newell1,2, Alan Chalil1, Kristopher D. Langdon1,2, Vahagn Karapetyan1, Matthew O. Hebb1, Fawaz Siddiqi1, Michael D. Staudt1,3,4. Cranial nerve and intramedullary spinal malignant peripheral nerve sheath tumor associated with neurofibromatosis-1. 30-Dec-2021;12:630
How to cite this URL: Christopher Newell1,2, Alan Chalil1, Kristopher D. Langdon1,2, Vahagn Karapetyan1, Matthew O. Hebb1, Fawaz Siddiqi1, Michael D. Staudt1,3,4. Cranial nerve and intramedullary spinal malignant peripheral nerve sheath tumor associated with neurofibromatosis-1. 30-Dec-2021;12:630. Available from: https://surgicalneurologyint.com/surgicalint-articles/11310/
Background: Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon but aggressive neoplasms associated with radiation exposure and neurofibromatosis Type I (NF1). Their incidence is low compared to other nervous system cancers, and intramedullary spinal lesions are exceedingly rare. Only a few case reports have described intramedullary spinal cord MPNST.
Case Description: We describe the clinical findings, management, and outcome of a young patient with NF1 who developed aggressive cranial nerve and spinal MPNST tumors. This 35-year-old patient had familial NF1 and a history of optic glioma treated with radiation therapy (RT). She developed a trigeminal MPNST that was resected and treated with RT. Four years later, she developed bilateral lower extremity deficits related to an intramedullary cervical spine tumor, treated surgically, and found to be a second MPNST.
Conclusion: To the best of our knowledge, this is the first report of cranial nerve and intramedullary spinal MPNSTs manifesting in a single patient, and only the third report of a confined intramedullary spinal MPNST. This unusual case is discussed in the context of a contemporary literature review.
Keywords: Intramedullary, Malignant peripheral nerve sheath tumor, Neoplasm, Spinal cord, Trigeminal nerve
Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas believed to arise from Schwann cells of the peripheral nerve sheath.[
Here, we report a case of spinal cord intramedullary MPNST in a patient with a history of NF1 and a prior trigeminal MPNST.
The patient was a 35-year-old female with familial NF1. At 3 years of age, she developed visual loss associated with an optic glioma that was treated with RT. She developed progressive left whole facial numbness and corneal irritation at the age of 30. No other cranial nerve abnormalities were noted at the time. This led to the finding of a large left trigeminal MPNST [
Magnetic resonance imaging of the trigeminal nerve and spinal intramedullary malignant peripheral nerve sheath tumors. Axial T1 with gadolinium cranial imaging demonstrating the left trigeminal nerve mass (a). Sagittal (b) and axial (c) T1 with gadolinium spinal imaging demonstrating the intramedullary mass. Sagittal T2-weighted imaging showing the same intramedullary mass with surrounding cord edema extending caudally and rostrally (d).
Histopathological analysis revealed a hypercellular neoplasm replacing normal peripheral nerve structure, with dominating densely cellular fascicular regions. Tumor cells showed focal positivity for S100 protein, CD57, and p53, but not EMA. The Ki-67 immunolabeling was high, up to 50% in select high-power fields. Overall, this was consistent with trigeminal MPNST.
Further imaging of the entire neuraxis was unremarkable at that time. She recovered to functional independence with no new neurological deficits and no restoration of her facial sensation. Surveillance magnetic resonance imaging (MRI) was performed every 6 months and failed to show recurrence. The patient was referred for genetic consultation after her first surgery.
Five years following the cranial surgery, she developed rapidly progressive bilateral lower extremity sensorimotor deficits leading to functional incapacitation over weeks. Her physical examination demonstrated diffuse weakness in the lower extremities, more pronounced proximally and on the left. There were diffuse hyperreflexia, a positive Babinski’s sign, and a T4 sensory level. Rectal tone remained intact, and the upper extremities appeared unaffected. MRI of the cervical spine revealed a contrast-enhancing intramedullary mass extending from C7 to T1 levels, with broader edematous changes in the spinal cord between C3 and T4 [
Surgical resection was planned with intraoperative somatosensory and motor evoked potential monitoring. Following C3–T2 bilateral laminectomies, a midline durotomy was performed and intraoperative ultrasound was used to localize the lesion at the level of C7. A midline myelotomy was performed revealing an infiltrative intramedullary mass with poorly defined borders. Tumor debulking was followed by an expansile duroplasty and C3–T2 posterior spinal instrumentation.
On pathological assessment, the biopsy consisted of a spindle cell neoplasm, forming interlacing cellular bundles of spindle cells (herringbone pattern) without distinct cellular borders [hematoxylin and eosin;
Histopathological imaging of the spinal intramedullary mass. H and E stained slides demonstrate a spindle cell neoplasm with interlacing cellular bundles (herringbone pattern) without obvious cellular borders and moderate pleomorphism (a). There is patchy staining with S100 protein (b). SOX10 (nuclear) stain is primarily lost (only sparse labeling) (c). INI1 is primarily retained, but there was focal lost throughout (d). The Ki-67 proliferation index is elevated (e). There are scattered fragments of CNS (spinal cord) parenchyma seen throughout (arrows), highlighted with GFAP (f). Scale bars (A: 200 μm) (b-f: 100 μm).
The patient remained neurologically unchanged and bedridden following surgery. Over the next year, she developed leptomeningeal deposits, presumed to be metastases, at the levels of the cerebral cortex and cauda equina which were treated with palliative local field RT. The patient was discharged to hospice and passed away at the age of 36.
This report represents the third case of a spinal intramedullary MPNST in the literature to date and is the first case in a patient with NF1 and previous trigeminal MPNST [
Paolini et al. reported the first case of an intramedullary MPNST at the C4–C5 level;[
In some reports, the spinal lesions arose de novo from the associated nerve roots, and in others, they were presumed to have metastasized from peripheral tissues. In a recent literature review of primary spinal intradural MPNST, recurrence and metastasis rates were high (54% and 45%, respectively), despite aggressive surgical resection and adjuvant RT.[
MPNSTs have a propensity to develop in association with NF1[
Given the limited adjuvant treatment options, efforts have been made in targeting pathways regulated by the NF1 protein or other associated mutations. Such targets include tyrosine kinase receptor,[
Lesions that arise in the context of NF1 are more likely to metastasize earlier than sporadic cases, although the rate of metastatic disease at presentation is similar among the two groups (10.4%).[
We have presented the case of a woman with a history of NF1 and remote trigeminal MPNST who presented with an intramedullary spinal cord MPNST. Interestingly, her trigeminal MPNST predated the spinal cord MPNST by 4 years, questioning whether the spinal lesion was metastatic or arose de novo. In addition, this lesion developed outside of the field of previous RT. To the best of our knowledge, this is the third reported case of intramedullary spinal cord MPNST, and the first case in a patient with NF1 and previous trigeminal MPNST. Close clinical follow-up and imaging of the entire neuraxis should be performed when clinically indicated in this challenging patient population.
The authors certify that they have obtained all appropriate patient consent.
There are no conflicts of interest.
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