The term "malignant peripheral nerve sheath tumor"(MPNST) comprises various entities including malignant schwannoma, neurofibrosarcoma, and neurogenic sarcoma. MPNSTs are rare with an incidence of 1:100,000. About half of the tumors occur in patients with type I neurofibromatosis12. Interestingly, about 10% of patients have a history of radiotherapy. Reliable data on survival is not available due to the rarity of the tumor and the heterogeneous patient population. One study reports a 5-year survival rate of 64% 3as compared with 72–78% for sarcomas4. The prognosis appears to depend on the tumor size (more unfavorable for tumors >5 cm), the histological grade and the resection margin in patients operated on2. There are two different grading classifications: One depends on the World Health Organisation (WHO) classification for soft-tissue tumors with a grading scale from I-III, the other one on the WHO classification for tumors of the nervous system with a grading scale IIIandIV56. The cell type from which MPNSTs are derived has not been yet identified. According to the WHO definition, MPNSTs are tumors that arise from a peripheral nerve or histologically show nerve sheath differentiation2. MPNST is a highly aggressive tumor with a high rate of local recurrence and pulmonary and visceral metastatic spread. Brain metastases are extremely rare and only eleven cases have been published since 1963. We report the case of a 60-year-old man presenting with the initial symptom of a focal seizure and in whom magnetic resonance imaging (MRI) demonstrated two intracerebral lesions.

The diagnosis of a MPNST is a clinical challenge for the physician regarding treatment options and additional diagnostic steps. In particular, if the tumor has spread into the Central Nervous System. No uniform criteria have been established for the treatment of MPNST outside the central nervous system. However, it is widely agreed that the extent of surgical resection is an important prognostic factor while no definitive data is available on the benefit of postoperative radiotherapy2. Irradiation seems to reduce local recurrence but does not affect the overall survival rate. Evidence for any relevant cytotoxic effect of chemotherapy (doxorubicin, ifosfamide) is not available7. Chemotherapy is performed only with palliative intent.

In most published cases of MPNST metastasizing to the cerebral parenchyma, the metastasis was removed microsurgically. The majority of reports are from Japan (Table 1). In some cases, surgical resection was followed by whole-brain irradiation. Our case is of interest because the patient had two cerebral metastases of which only one was removed surgically. It is thus possible to compare the outcome after combined surgery and radiotherapy with the outcome after irradiation only. In our case, there has been local tumor control of both metastases for 14 months so far. Therefore we conclude that whole-brain irradiation without prior surgical removal or a radiosurgical approach in treating cerebral metastasis of a MPNST is the best choice.

MPNST in general has an unfavorable prognosis with a 5-year survival rate of only 64%. Survival is even much shorter in patients with a brain metastasis and is not affected by the therapeutic approach. A definitive appraisal of the situation is difficult because only few patients have been treated so far. One patient survived for 18 months without treatment 8 whereas another died a few months after total resection of a brain metastasis9. In our case, resection and irradiation have so far suppressed local cerebral recurrence for a total of 14 months while there has been progression of the other distant metastases. Given the rapid tumor progression in our case, cautious therapy with little harm to the patient is indicated.

Beside the clinical challenge of a new diagnose MPNST, the pathologist has to deal with a great work up in the beginning to provide the physician with a correct diagnosis. The histological diagnosis of MPNST requires careful differentiation from a number of tumor entities with similar histologic features. In general, MPNST cells have either an epithelioid or spindled architecture with gradual transitions between the two. The spindled type must be carefully differentiated from other spindled-cell soft tissue tumors, in particular fibrosarcoma. An immunoreaction to S-100 as in our case excludes a fibrosarcoma and underlines the close association of MPNST with the nerve sheaths910. Another tumor to be considered in the differential diagnosis in our patients was malignant melanoma because some cells were found to contain melanin on microscopic inspection. However, a malignant melanoma could be excluded because there was no immunoreaction to LU-5 (cytokeratin), which is only expressed in some epitheloid variants of melanomas. Whereas vimentin positivity as in this case, occurs also in high malignant melanomas. Nevertheless, evidence of a basal lamina by electron microscopy investigation strongly indicates the tumor as a MPNST by nerve sheath origin. In the case presented here, the tumor was further characterized as a melanocytic MPNST because the melanin-containing cells were found to be positive for HMB45.

The author(s) declare that they have no competing interests.

J.T.: collected clinical data, wrote particular parts of the paper, performed the reference search

K.M.: histological evaluation, wrote the histology part

G.N.: performed all MRI's, included the figures, wrote the MRI findings

J.L.: responsible for the irradiation of the patient, contribute in the follow-up of the patient and in the revision of the manuscript

J.V.: contributed in data collection, revision and translation of the manuscript, performed surgery