Pure intracranial, intraparenchymal presentation of a malignant peripheral nerve sheath tumour: A rare case
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.263190
Source of Support: None, Conflict of Interest: None
Malignant peripheral nerve sheath tumours (MPNST) are soft tissue sarcomas derived from peripheral nerves. Histopathologically, MPNST arise from differentiated Schwann cells embedded in a varied environment comprising perineurial-like cells, fibroblasts, vascular cells and mast cells. Cross-sectional studies have shown that 1–2% of patients with neurofibromatosis develop malignant peripheral nerve sheath tumours, and that the lifetime risk of malignancy in these patients is significantly higher than previously estimated.,,
Malignant peripheral nerve sheath tumours occur between fourth and sixth decades of life with a male predilection, the male to female ratio being 2.5:1. It can occur anywhere in the body, but most often occurs in the deep tissue of the limbs and trunk, involving the brachial and lumbar plexuses. As mentioned, these tumours occur more frequently in neurofibromatosis and persons who have undergone radiation therapy for cancer., However, most people have no risk factors for the disease. Intracranial MPNST is a rare and highly malignant tumour. The incidence of this subtype is approximately 0.001%.,,, Most lesions occur sporadically. The prognosis of the tumour is extremely poor and they are considered among World Health Organisation (WHO) grade IV tumours. MPNST is typically treated surgically but for incomplete, unresected tumours, chemotherapy or radiation therapy should be considered. The mean time of recurrence or metastasis is around 12 months.
We hereby report a case of pure intracranial, intra-parenchymal MPNST located in the left parietal lobe.
A 44-year old female patient, a house-wife, presented with the chief complaint of left frontal and parieto-occipital headache 15 days back, which was insidious in onset, continuous in nature, non-pulsatile/thunder clapping type, not associated with giddiness/loss of consciousness/seizures/visual disturbances during such episodes. The pain was not relieved by medications, and persisted till late in the evening. The patient also gave a history of vomiting twice, the next day. No relevant past medical or surgical history was reported.
On examination, the patient was conscious, alert and well oriented. All her vital parameters were normal. No neurocutaneous markers were noted. The neurological examination was unremarkable except for symptoms and signs suggestive of raised intracranial pressure (ICP) with early papilledema.
All baseline investigations were found to be within normal limits. Chest X-ray and ultrasonogram of the abdomen did not show signs of any other lesion.
MRI brain showed a well-defined T2 isointense lesion of size 3.6 × 3.4 cm in the left parietal lobe with surrounding extensive perilesional oedema and mild mass effect. There was intense enhancement on contrast administration and magnetic resonance spectroscopy (MRS) showed [Figure 1] a high choline peak and absence of N-acetyl aspartate (NAA) peak [Figure 2]. The lesion was seen causing effacement of the occipital horn of the left lateral ventricle with a midline shift of 4 mm to the right.
The patient underwent a left parietal craniotomy and gross total resection of the tumour. The post-operative period was uneventful [Figure 3]. Grossly, the lesion was rubbery, moderately vascular and the cut-section showed grey-white with focal grey-black areas [Figure 4]. Histologically, it was reported as malignant peripheral nerve sheath tumour WHO grade IV. Microscopic examination showed spindle shaped cells, arranged in a fascicular with focal herringbone pattern. The tumour had foci of extremely high cellularity, eosinophilic cytoplasm and prominent nucleoli, nuclear pleomorphism with a fascicular pattern, hyperchromatic nuclei, numerous mitotic figures and extensive necrosis. Atypical mitosis was noted. The immunohistochemistry was positive for S-100 and vimentin and negative for epithelial membrane antigen (EMA) and glial fibrillary acidic protein (GFAP). The Ki67 labelling index was over 20% [Figure 4].
Postoperatively, the patient clinically improved well and ICP significantly reduced with no neurological deficits. She was discharged from our hospital and was referred for radiotherapy with periodic follow-up. Until 9 months follow-up, the patient had no fresh deficits or recurrence.
Peripheral nerve sheath tumours are benign or malignant lesions arising from peripheral nerve or nerves showing such differentiation. Their aetiology is unknown. Neurofibromatosis gene-NF2 mutations predisposes to the development of a schwannoma affecting the spine and intracranial nerves. While sporadic MPNST is most often seen between the fourth and fifth decades of life, in NF1, they present a decade earlier. Intracerebral schwannomas show a slight male predominance whereas malignant intracerebral nerve sheath tumours show no gender predominance.
Schwannomas within the neural axis are uncommon. If present, an intramedullary location is more likely than an intracerebral location. Malignant intracerebral nerve sheath tumours (MINST) arise from aberrant Schwann cells and other mesenchymal cells in the perivascular nerve plexuses around large blood vessels in the subarachnoid space, from adrenergic nerve fibres innervating cerebral arterioles, in the meningeal branches of trigeminal nerve, or from the pluripotent cells of neural crest origin.,, Hemispheric intra-parenchymal localisations are quite rare. However, if they arise within the intracerebral compartment, a supratentorial location is more common. Intra-cerebellar localization is even more exceptional.,,,, [Table 1] summarises the data of patients with MPNST presenting at various other intracranial sites, the treatment given and their outcomes, as mentioned in each article.
This tumour represents 8% of all primary brain tumours. In 1977, one case was reported by Komminoth. Since then only one other case has been published in 1987 by Sarkar. Only 19 cases until 2014 have been reported in the world literature.,,
Histopathologically, these tumours are characterised by the presence of pale spindle cells often arranged in fascicles with alternating cellular and more myxoid areas, and a high mitotic index. Immunohistochemistry shows S-100 positivity in about 50–70% cases.,
An intracerebral peripheral nerve sheath tumour not associated with cranial nerves is extremely rare and highly malignant with the overall survival being poor., Compared to MPNSTs from all body sites, which arise more frequently with associated radiation exposure, our patient did not have any other focus of tumour with no features of NF1 on evaluation and no history of prior radiation exposure before the onset of the disease.
As the central nervous system is devoid of peripheral nerve sheath cells, the pathogenesis of intracranial MPNST is not clearly understood and those not associated with a cranial nerve have been explained by several theories.
Management of intracranial MPNSTs is firstly surgical, with adjuvant radiotherapy and chemotherapy treatments being controversial. The latter modalities are administered to delay the onset of recurrence, especially in NF-I patients.,
Malignant peripheral nerve sheath tumours have a high metastatic potential and generally a poor prognosis. The lungs, soft tissues, bones, liver and brain are all documented sites of haematogenous metastases. Metastasis to the spinal cord is more common. Local recurrence rates range from 30% to 60% even in patients who underwent complete resection.,, MPNSTs are graded between World Health Organisation grade II and IV lesions, but there is no prognostic correlation between the grade and survival., The most reliably determined adverse prognostic factor across all studies is a large tumour size at presentation.,,
This heterogeneously enhancing lobar mass has in its differential diagnosis, a glioblastoma, anaplastic meningioma, malignant melanoma and gliosarcoma. After surgical excision, the presence of tumor at the resected margins and its local recurrence portends a poorer prognosis, as suggested by multiple retrospective series. Although radiotherapy provides a local control and may delay the onset of recurrence, it has little effect on long term survival rates. MPNST is chemo-insensitive, and therefore, chemotherapy is confined to the treatment of metastatic disease.
The combined use of conventional fractioned radiotherapy and stereotactic gamma knife radiosurgery has shown stabilization of this aggressive tumour. A close post-operative follow-up is essential especially with NF-I patients to detect recurrence.,
The pathogenesis of intracerebral MPNSTs still remains poorly understood. MPNSTS are at present treated as any other soft-tissue sarcomas, because they are too rare to perform trials with a sufficient number of patients. The routine chemotherapy regime followed for other soft-tissue sarcomas does not help in improving the outcome of MPNST, i.e. doxorubicin and ifosfamide, which are reported to have only partial response rates of about 20–25%. Advances in molecular biology of MPNSTs may help to provide new targeted therapies in the future.,
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]