A 6-year-old girl from Medellin, Colombia, South America, presented with twenty-five days of left-sided headache, vomiting, and episodes of syncope lasting roughly five seconds. The patient had no other medical history of significance. She had no café au lait spots, and no other tumors or masses in other body sites. Neurological examination revealed no focal deficits. An MRI scan showed a large intra-axial left parietal lobe mass with significant surrounding edema. The mass did not appear to originate from the dura; it did reach or breach the pia on the parietal convexity, and medially close to the falx. The falx was pushed by the mass effect of the tumor and was clearly separate from it. (Fig 1a ). A surgical excision was done in Colombia, and a tentative diagnosis made. The slides and selected blocks were sent to the University of Missouri for consultation. Since the time of surgery, the patient has been treated with radiation (thirty treatments) and has done extremely well. Neurologically she is almost completely normal, and her mother reports that the patient is asymptomatic and leading a normal life attending school. The resected soft tissue fragments were grossly hemorrhagic, pink and yellow. Histologically, the tumor was composed of sheets of spindle cells, with very little in the way of distinctive patterns. Some of the larger pieces had alternating dense and hypodense fascicles arranged in vague marbled or herringbone patterns. (Fig 1b, 1c) The tumor was highly cellular with small foci of necrosis. Adjacent gliotic brain was sharply-demarcated from the tumor, without any single-cell (glioma-like) invasion. The tumor was well vascularized but had no vascular hyperplasia and did not have a hemangiopericytoma-like staghorn vascular pattern. The neoplastic cells had large fusiform nuclei with areas of marked pleomorphism; most nuclei showed clumped chromatin and prominent nucleoli. Mitotic activity was brisk, with a Ki-67 proliferation index of at least 75%, approaching 100% in certain areas. (Fig 2a) The tumor cells were strongly immunopositive for Vimentin and p53 (Fig 2b, 2c); a CD56 (NCAM) immunostain was diffusely moderately positive (Fig 2d). The tumor was negative for Smooth Muscle Actin, Skeletal Muscle Actin, S100 protein, Desmin, GFAP, Synaptophysin, Chromogranin,NSE, Epithelial Membrane Antigen (EMA) and Cytokeratin (CK). A CD34 immunostain highlighted endothelial cells in tumor blood vessels, but not the tumor cells themselves (Fig 2e). Additional immunostains showed strong cytoplasmic positivity for neurofilament protein (antibody RMDO-20 to NF-M) in a few of the tumor cells and in some of entrapped normal neurons. A reticulin stain showed minimal fibrosis. A CD31 immunostain highlighted the endothelial cells in tumor blood vessels, similar to the CD34, and also did not mark the tumor cells. Finally, a Nestin immunostain was strongly positive (Fig 2f). What is the diagnosis? Malignant peripheral nerve sheath tumor (MPNST) is a malignant spindle cell neoplasm which accounts for 5–10% of all soft tissue sarcomas. MPNST is thought to arise from various elements of the nerve sheath (particularly the Schwann cell) and often, but not always, arises from a peripheral nerve. MPNST may occur spontaneously or in association with Neurofibromatosis Type 1 (NF1). Roughly 25%–50% of MPNST occur in patients with NF1 7. Most MPNSTs are associated with a major nerve trunk and present as enlarging masses. Clinical symptoms vary depending on location. Although MPNST has been described in childhood, its incidence is rare. Intracerebral MPNST is even rarer, and has been divided into those tumors that are associated with cranial nerves, and those which are not (such as our case). There have been a total of 18 reported cases of MPNST not associated with cranial nerves 2, excluding our case. Radiologic findings in intracerebral MPNST include a mass in any part of the cerebrum, which usually has marked surrounding edema. Histologically, the mass is a spindled, highly cellular lesion with marked nuclear pleomorphism, prominent nucleoli, and brisk mitotic activity. The overall architecture often resembles that of a fibrosarcoma, but with less organization; MPNST may show marbling or herringbone arrangements. The immunohistochemical profile is also variable, although most MPNSTs are immunopositive for vimentin, S-100 protein, p53 and nestin, and are almost always negative for keratins. CD34 may occasionally be expressed in MPNST. Because of the variability in histologic and immunostain profiles, the diagnosis of MPNST is often challenging. In this case, several differential diagnoses were considered, including monophasic synovial sarcoma (MSS), malignant solitary fibrous tumor (MSFT), fibrosarcoma, and other high-grade sarcomas. Briefly, a high grade glioma was considered, but a glioma is almost never as sharply demarcated from adjacent pieces of brain as this tumor is. The possibility of a glioma diagnosis is further ruled out by negative immunostains for GFAP and S100 protein. Negative immunostains for desmin, smooth muscle actin, and skeletal muscle actin helped to rule out diagnoses of leiomyosarcoma and rhabdomyosarcoma, and negative immunostains for CK and EMA ruled out a diagnosis of MSS, most of which have at least a little expression of one or both of these markers. A CD31 and CD34 were both negative in the tumor cells, ruling out MSFT. A strongly positive CD56 (NCAM) immunostain argued against a diagnosis of fibrosarcoma, which is considered a diagnosis of exclusion, and favored a diagnosis of MPNST or MSS. A strongly positive p53 favored MPNST, and a strongly positive nestin in this context established the diagnosis of MPNST 3, 5. Intracerebral MPNST is presumed to arise from peripheral nerves which traverse the cerebral white matter, probably with blood vessels. Several possibilities for the origin of these peripheral nerves exist. It is known that Schwann cells accompany peripheral nerves in the dura and may penetrate the brain alongside the blood vessels they accompany. It is conceivable, therefore, that a Schwann cell tumor could originate from an intracerebral perivascular nerve. Additional hypotheses include MPNST arising from adrenergic nerve fibers, pluripotential cells within the brain, displaced neural crest cells, and meningeal branches of the trigeminal nerve 2, 4. MPNST is a highly aggressive tumor with a generally poor prognosis. The addition of adjuvant therapies has improved survival, but even so, the 5-year survival rate is 52%, and the rate drops lower if good surgical margins cannot be achieved 7. For intracranial MPNST, the reported median overall survival is 9 months 1, and patients with NF1 have an even lower survival rate 8. Therapy for intracranial MPNST includes gross total resection as well as adjuvant radiation therapy, although treatment is not standardized. Chemotherapy is used in patients with systemic recurrence 6. Interestingly, a recent study found that females are less likely to develop intracranial MPNST and if they do, they have a better prognosis 1.