MALIGNANT TRANSFORMATION OF CRANIAL NERVE SCHWANNOMA AFTER RADIOSURGERY - CASE REPORT

Abstract

We describe an unusual case of malignant transformation of benign cranial nerves schwannoma eleven months after surgery and five months post radiotherapy. There has been no evidence of recurrence after 5 years follow-up. This early malignant transformation of a schwannoma involved cranial nerves IX, X, XI. Due to the uncommon presentation and the uncertainty of the actual role of the radiation on the tumor behavior, the report of this case was considered clinically important.

Introduction

Most intracranial nerve sheath tumours are histologically benign; malignant transformation is unusual. Malignant nerve sheath tumours are most frequently seen within the context of neurofibromatosis1. Malignant transformation of a benign intracranial nerve sheath tumour has been reported on a few occasion and most commonly affected cranial nerves V, and the acoustico-vestibular and facial nerves2. We report a case of schwannoma involving the cranial nerves IX, X, XI with pathological evidence of malignant transformation eleven month from the first microsurgical resection and five month after stereotactic radiosurgery.

Case Report

History and Examination

A 42-year-old female teacher presented to our department with the main complaint of progressive hearing loss in the right ear. On neurological examination, she was found to have nystagmus, right uvula deviation, right facial paresis (grade 3) and sensorineural hearing loss in the right ear. The gag reflex was intact. There were no stigmata of neurofibromatosis.T1-weighted Magnetic Resonance Imaging (MRI) with contrast revealed a 4x3 cm non-homogeneously enhanced right cerebellopontine angle mass. The mass contained an intracranial cystic component and extension into the eroded jugular foramen with compression of the brainstem and compression of the fourth ventricle figure 1.The working diagnosis was a mixed nerve schwannoma (lower cranial nerves) with an extradural component.

figure 1. Enhanced T1 magnetic resonance imaging showing the original tumor.

Surgical procedure and post operative course

A right suboccipital retrosigmoid craniotomy was performed and total microsurgical resection of the intradural portion was achieved. The diagnosis of benign schwannoma was confirmed on histological examination figure 2; Gamma knife surgery (GKS) was planned for the removal of the small extradural residual tumour in the jugular foramen. No visible residual enhancing tumour was present intracranially on postoperative computed tomography. Follow up MRI 2 month later confirmed the complete resection of the intracranial portion of the tumour figure 3.

figure 2. Pathological findings of the original tumor.

figure 3. Post operative Enhanced T1 MRI (a) Axial view showing complete resection of cerebellopontine angle mass (b) Coronal view demonstrating residual extra cranial tumour.

The patient was admitted to the stereotactic radiosurgery (GKS) unit six months later. Preoperative stereotactic MRI revealed a recurrent intramural cystic tumor at the original site figure 4. The GKS was delivered to the extracranial tumor margin (peripheral dose 15 Gy 50%).

figure 4. Enhanced T1 magnetic resonance imaging performed before the radiosurgery .

The patient underwent surgical removal of the tumour five month later figure 5. Histologic examination was consistent with a spindle-shaped pattern with hypercellularity and pleiomorphic nuclei figure 6. On immunohistochimical staining the Ki67 reached 15% positivity. The careful review of the histopathological specimen was consistent with malignant partially epitheloid nerve sheath tumour. The residual tumour in the jugular foramen showed no sign of recurrence on MRI at 5 years follow up figure 7. The patient remains clinically stable and has returned to work.

figure 5. Axial Enhanced T1 weighted MR image obtained after the reoperation .

figure 6. Pathological findings of the recurrent tumor .

figure 7. Magnetic resonance imaging obtained 5 years after radiosurgery .

Discussion

As defined by the World Health Organization, malignant nerve sheath tumors are malignant tumours showing a nerve sheath differentiation, with the exception of tumors originating from the epineurium or the nerve vasculature1. A number of terminologies, including malignant schwannoma, malignant neurilemoma, neurofibrosarcoma, and neurogenic sarcoma, have been used to describe this entity3,4,5. These tumours are treated as a subcategory of soft tissue sarcomas, comprising 3 to 10% of all such tumors6. Most cases arise from peripheral nerves of the extremities and seldom involves the cranial nerves, with approximately 62 cases of intracranial malignant nerve sheath tumour reported in the English-language literature to date7. Unlike their extracranial counterparts, intracranial malignant nerve sheaths tumors are most commonly sporadic, and appear to have a male predilection8,9. There are only a few reports of malignant transformation of an intracranial nerve sheath tumour. Nerves that have been reported include the trigeminal, facial and vestibular nerve9,10,11,12. This presentation therefore, is uncommon and hence the need for vigilance.

The lesion recurred six months after the first microsurgical resection with histological evidence of malignant transformation five months after Gamma knife surgery (GSK). The previous resection from the same site showed schwannoma with no evidence of malignancy. Mclean et al suggested the potential risk of benign cranial nerve tumour progression in a report of malignant transformation of vestibular schwannoma 11 month after initial resection3. However in that case the histopathological findings of the original tumour were not definitively benign. Few other cases of spontaneous malignant transformation have been published2,5,10. Son et al reported the malignant recurrence of a vestibular schwanonma two months after total microsurgical resection12. The authors performed retrospective careful examinations of the slide of the original tumor which did not display any malignant feature. This suggests that a multistage sequence occurs for tumor progression in these neoplasms. The molecular events involved from a benign nerve sheath tumour to a malignant nerve sheath tumor, are still unknown. An issue with all these cases is the possibility of intratumoral heterogeneity.

Long term post radiation malignant change of benign nerve sheath tumour is well documented9,13,14,15. In their evaluation of the very long term efficacy of fractionated radiotherapy in the treatment of vestibular schwannomas, Maire et al suggested the possible role of this type of radiation in the malignant transformation of benign nerve sheath tumour after many years9. There have also been 6 cases of pathologically confirmed cases of malignant transformation of benign nerve sheath tumour after stereotactic radiotherapy in the literature to date, with a mean latency period of 5.8 years, supporting the possibility that radiosurgery may play a causative role in the transformation4,13,14,15. In this case the malignant changes were observed histologically 5 months after radiosurgery and the recurrence was already noted on the pre-radiosurgery MRI. In their 2001 report of recurrent vestibular schwannoma with malignant transformation, Hanabusa et al found mitotic changes on histopathological examination 6 month after GSK16. This was the shortest reported latency period for a documented malignant transformation following radiosurgery, found in the literature.

Stereotactic radiosurgery remains an effective adjuvant to subtotal microsurgery resection of intracranial nerve schwanomas14. In their review of the 61 cases of intracranial MNST published in the literature, Voorhies et al concluded that radiation seemed to provide a survival benefit regardless of the extent of resection. They found no 5-year survivor in non radiated group7. This conclusion tends to be confirmed by our case of malignant transformation treated with stereotactic radiosurgery and a repeat surgery with a good result at 5-year follow up.

Conclusions

Benign nerve sheath tumour has a rare but potential risk of spontaneous malignant transformation.