Journal of Clinical Neuroscience xxx (2014) xxx–xxx

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Case Report

Radiation induced malignant peripheral nerve sheath tumour of the second cervical nerve Bryden Dawes a,⇑, Jonathan Clark b, Stephen T. Byrne a, Renate Kalnins b, Augusto Gonzalvo a, Myron Rogers a a b

Department of Neurosurgery, Austin Health, The University of Melbourne, 145 Studley Road Heidelberg, VIC 3070, Australia Department of Anatomical Pathology, Austin Health, The University of Melbourne, VIC, Australia

a r t i c l e

i n f o

Article history: Received 5 February 2014 Accepted 12 February 2014 Available online xxxx Keywords: Cervical nerve Dumbbell tumour Malignant peripheral nerve sheath tumour Nerve sheath tumour Radiation therapy

a b s t r a c t We report a 44-year-old with progressive quadriparesis due to a dumbbell malignant peripheral nerve sheath tumour (MPNST) of the second cervical nerve, 17 years after whole brain radiotherapy for a pineal germinoma. To our knowledge this is the first case of radiation induced high cervical MPNST arising from a benign neurofibroma. Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.

1. Case report A 44-year-old man was referred to our hospital following a 2 month history of progressive quadriparesis and gait disturbance. His significant past history included a pineal germinoma resected at the age of 27 with adjuvant whole brain radiotherapy to a dose of 50 Gray, with specific field documentation not available. He had no family history or peripheral stigmata of neurofibromatosis type 1 (NF1). His preoperative MRI demonstrated a C2 dumbbell lesion with intradural, extradural and paravertebral components causing ventral compression of the cervicomedullary junction. The lesion was isointense on both T1 and T2-weighted sequences with heterogeneous gadolinium contrast enhancement (Fig. 1). The patient underwent a right far lateral approach without condylectomy, C1 and C2 laminectomy and exposure of the vertebral artery without transposition. Subtotal resection of the tumour was achieved with only the component adherent to the ventral aspect of the cord and encasing the anterior spinal artery left in situ (Fig. 2). Intraoperative frozen section histology was suggestive of a benign peripheral nerve sheath tumour. Subsequent histologic examination of formalin-fixed tissue confirmed a component of neurofibroma. This was a loosely cellular myxoid tumour composed of bland spindle cells showing staining of scattered single ⇑ Corresponding author. Tel.: +61 3 9496 5000; fax: +61 3 9496 2533. E-mail address: [email protected] (B. Dawes).

cells for S100 and occasional neurofilament positive neural fibres. In addition there was a component of highly cellular fascicular spindle cell tumour with areas of necrosis, mitotic count up to 15 per 10 high power fields and very patchy staining for S100 (Fig. 3). Accordingly a diagnosis of malignant peripheral nerve sheath tumour (MPNST) arising in a neurofibroma was made. The postoperative period was complicated by hemiparesis and wound dehiscence requiring a rotational skin flap and split-skin graft, delaying planned radiotherapy. Despite further focal radiotherapy, the patient developed an aggressive intramedullary recurrence and died 2 months postoperatively. 2. Discussion We present a patient with radiation therapy (RT) induced MPNST of the second cervical nerve 17 years following cranial irradiation. To our knowledge, this is the first documented case of an intradural high cervical MPNST arising from neurofibroma secondary to radiation exposure. MPNST are a relatively rare soft tissue sarcoma with 50–60% of tumours associated with NF1 [1]. They may occur de novo, or following RT exposure with up to 10% of MPNST associated with prior irradiation [2]. RT has been implicated in the development of a number of soft tissue sarcomas including malignant fibrous histiocytoma, angiosarcoma, fibrosarcoma, leiomyosarcoma and MPNST [3]. The diagnosis of RT induced sarcoma is based on criteria described by Cahan et al. in 1948 [4]. They determined that there must be

http://dx.doi.org/10.1016/j.jocn.2014.02.017 0967-5868/Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Dawes B et al. Radiation induced malignant peripheral nerve sheath tumour of the second cervical nerve. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.017

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Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx

Fig. 1. Preoperative coronal (A) T1-weighted and (B) T2-weighted MRI showing a C2 dumbbell lesion with intradural, extradural and paravertebral components.

Fig. 2. (A) Sagittal T1 + contrast immediately postoperatively (B) Sagittal T1 + contrast and (C) Coronal T1 + contrast seven weeks postoperatively demonstrating intramedullary recurrence

evidence of an underlying benign lesion, a history of radiation exposure with the lesion occurring within the radiation field, an asymptomatic latent period and finally sarcomas must be proven histologically. MPNST has a very poor prognosis with 5 year survival ranging from 35–50% [5]. Furthermore, LaFemina et al. [5] and Gladdy et al. [6] demonstrated trends towards even worse disease-free survival for RT associated MPNST compared with sporadic MPNST, albeit in unmatched cohorts and in small sample sizes of 14 and 10, respectively. George et al. [7] reported a patient with malignant transformation of a C2 schwannoma in a 39-year-old man 11 years after cervical radiotherapy for lymphoma. Following resection of a benign lesion, recurrence was seen 1 year later with malignant transformation to MPNST. He underwent reoperation but died a few months postoperatively. Few patients with intraspinal sporadic and NF1 related MPNST affecting the second cervical nerve have been reported in the literature. Zhu et al. [8] presented

two patients as part of their larger spinal MPNST case series. They were able to achieve complete surgical resection in both patients, however experienced a similar outcome to that described here, with a survival of less than 2 months in the single patient with high grade MPNST. Intraspinal MPNST of the high cervical spine represent a surgical challenge. Despite the very poor prognosis of MPNST, complete surgical resection has been shown to improve disease-free and overall survival [9] with en bloc resection recommended in extraspinal tumours. Intradural MPSNT are not suitable for en bloc resection and at best macroscopically complete resection may be feasible if neurovascular structures are not encased in the tumour. Surgical decision-making is further complicated by the focal nature of malignant cells. As demonstrated in our patient, intraoperative frozen section histology may be subject to sampling error and thus decision-making may be incorrectly based on a presumption of benign pathology. In our patient, a less aggressive resection would

Please cite this article in press as: Dawes B et al. Radiation induced malignant peripheral nerve sheath tumour of the second cervical nerve. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.017

Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx

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Fig. 3. (A) Focus of malignant peripheral nerve sheath tumour (MPNST) (arrowhead) arising within neurofibroma (asterisk), (haematoxylin and eosin). (B) High power view of MPNST comprising mitotically active spindle cells (arrowhead) arranged in dense fascicles (haematoxylin and eosin). (C) S100 immunohistochemistry demonstrating the characteristic patchy staining of MPNST. (D) Ki67 immunohistochemistry demonstrating positive staining in approximately 50% of tumour cells.

have been performed if the malignant diagnosis were evident intraoperatively. 3. Conclusion Intraspinal MPNST of the high cervical spine is an extremely rare tumour with a very poor prognosis. To our knowledge we report the first documented patient with high cervical MPNST arising from a benign neurofibroma following radiotherapy. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References

[2] Ducatman BS, Scheithauer BW, Piepgras DG, et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 1986;57: 2006–21. [3] Cha C, Antonescu CR, Quan ML, et al. Long-term results with resection of radiation-induced soft tissue sarcomas. Ann Surg 2004;239:903–9 [discussion 909–10]. [4] Cahan WG, Woodard HQ, Higinbothan NL, et al. Sarcoma arising in irradiated bone; report of 11 cases. Cancer 1948;1:3–29. [5] LaFemina J, Qin LX, Moraco NH, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol 2013;20:66–72. [6] Gladdy RA, Qin LX, Moraco NH, et al. Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? J Clin Oncol 2010;28:2064–9. [7] George B, Lot G. Neurinomas of the first two cervical nerve roots: a series of 42 cases. J Neurosurg 1995;82:917–23. [8] Zhu B, Liu X, Liu Z, et al. Malignant peripheral nerve sheath tumours of the spine: clinical manifestations, classification, treatment, and prognostic factors. Eur Spine J 2012;21:897–904. [9] Ren X, Wang J, Hu M, et al. Clinical, radiological, and pathological features of 26 intracranial and intraspinal malignant peripheral nerve sheath tumors. J Neurosurg 2013;119:695–708.

[1] Grobmyer SR, Reith JD, Shahlaee A, et al. Malignant Peripheral Nerve Sheath Tumor: molecular pathogenesis and current management considerations. J Surg Oncol 2008;97:340–9.

Please cite this article in press as: Dawes B et al. Radiation induced malignant peripheral nerve sheath tumour of the second cervical nerve. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.017