malignant peripheral nerve sheath tumors ( mpnst ) , which are comprised of 5 to 10% of all soft - tissue sarcoma , often occur in the near proximal extremity at a nerve trunk such as sciatic nerve , brachial plexus , or sacral plexus .
they have a distinct association with the neurofibromatosis type 1 and occur in 3 - 15% of nf1 patients and a high incidence of tumor is related to the mutation of the nf1 gene9 ) . on the other hand ,
a primary malignant intracerebral nerve sheath tumor ( minst ) is quite rare , with only 8 cases1,2,4,10,12,13,15,16 ) documented in english - language literature .
a 13-year - old boy was hospitalized due to the headache on the right side of his head , which began 2 weeks ago and the vomiting , which began a week ago .
there was no evidence of neurofibromatosis such as neurofibroma , caf au lait spot , lisch nodule , optic glioma , distinctive bony lesion ( dysplasia of the sphenoid bone or long bone cortex ) and freckle in the groin or axilla with no family history of neurofibromatosis .
brain magnetic resonance imaging ( mri ) revealed about 6.7 cm diameter , a well defined highly enhancing mass in the right frontal lobe ( fig .
1 ) . the preoperative differential diagnoses were glioblastoma multiforme , anaplastic astrocytoma , and malignant meningioma .
macroscopically , it was a well - circumscribed yellowish nodular round mass having gelatinous surface without dural attachment ( fig .
it was intra - parenchymal tumor and had a distinct cleavage plane in the superficial brain parenchyma , but not in the deeper portion .
microscopically , the tumor was highly cellular and mainly consisted of spindle cells in interlacing and interwoven fascicles .
each tumor cell had a fusiform nucleus and aligned in a convoluted form with a moderate degree of mitotic activity and a high nuclear - to - cytoplasmic ratio .
3 ) , but negative for glial fibrillary acidic protein ( gfap ) , cd34 , synaptophysin and desmin . these histological and immunohistochemical findings supported the diagnosis of a primary minst .
thirty times of fractionated whole - brain radiation were performed with 5760 cgy over the period of 6 weeks after surgery .
brain mri follow - up examination was performed every six months , but there was no evidence of tumor recurrence .
brain mri at 50 months after his first surgery revealed a 1.01.0 cm of well - defined enhancing mass in the right frontal convexity and leptomeningeal enhancement in the right frontal area ( fig .
the histopathological examination showed a primary minst , which was consistent with the histopathological results from the first surgery .
the brain mri at four months after second surgery revealed a tumor of 1.00.5 cm in size in the right anterior frontal convexity and pachymeningeal enhancement in the right frontal area ( fig .
as the patient 's guardian wanted to treat the patient in another hospital , so the patient was transferred to another hospital .
as the tumor was repeatedly relapsed despite the gtr which was performed twice before , radiation therapy and chemotherapy were performed according to the korean society for pediatric neuro - oncology ( kspno)-s081 protocol , which can be used for a high - grade brain tumor13 ) .
thirty times of fractionated radiation were carried out with 6000 cgy after his third surgery and 4 times of combination chemotherapy with vincristine ( 1.5 mg / m iv push , day 0 , 7 ) , etoposide ( 75 mg / m in normal saline dose 2.5 times iv over 2 hours , day 0 - 4 ) , carboplatin ( 300 mg / m in normal saline 125 ml / m iv over 1 hour , day 0 , 1 ) , and ifosfamide ( 1500 mg / m in dextrose water 200 ml / m with mesna ( 300 mg / m iv over 1 hour , day 0 - 4 ) were applied . the irregular enhancing lesion ( 3.04.0 cm )
was found in a brain mri at six months after the third surgery ( fig .
was found to be smaller than the previous one in the brain mri at thirteen months after the third surgery , this lesion is considered to be the result of radiation injury rather than tumor recurrence ( fig .
5c ) . he is still alive at 77 months after his first surgery and complaining of mild headache and dizziness , but there are no other neurological abnormalities .
a 13-year - old boy was hospitalized due to the headache on the right side of his head , which began 2 weeks ago and the vomiting , which began a week ago .
there was no evidence of neurofibromatosis such as neurofibroma , caf au lait spot , lisch nodule , optic glioma , distinctive bony lesion ( dysplasia of the sphenoid bone or long bone cortex ) and freckle in the groin or axilla with no family history of neurofibromatosis .
brain magnetic resonance imaging ( mri ) revealed about 6.7 cm diameter , a well defined highly enhancing mass in the right frontal lobe ( fig .
1 ) . the preoperative differential diagnoses were glioblastoma multiforme , anaplastic astrocytoma , and malignant meningioma .
macroscopically , it was a well - circumscribed yellowish nodular round mass having gelatinous surface without dural attachment ( fig .
it was intra - parenchymal tumor and had a distinct cleavage plane in the superficial brain parenchyma , but not in the deeper portion .
microscopically , the tumor was highly cellular and mainly consisted of spindle cells in interlacing and interwoven fascicles .
each tumor cell had a fusiform nucleus and aligned in a convoluted form with a moderate degree of mitotic activity and a high nuclear - to - cytoplasmic ratio .
3 ) , but negative for glial fibrillary acidic protein ( gfap ) , cd34 , synaptophysin and desmin . these histological and immunohistochemical findings supported the diagnosis of a primary minst .
thirty times of fractionated whole - brain radiation were performed with 5760 cgy over the period of 6 weeks after surgery .
brain mri follow - up examination was performed every six months , but there was no evidence of tumor recurrence .
brain mri at 50 months after his first surgery revealed a 1.01.0 cm of well - defined enhancing mass in the right frontal convexity and leptomeningeal enhancement in the right frontal area ( fig .
the histopathological examination showed a primary minst , which was consistent with the histopathological results from the first surgery .
the brain mri at four months after second surgery revealed a tumor of 1.00.5 cm in size in the right anterior frontal convexity and pachymeningeal enhancement in the right frontal area ( fig .
as the patient 's guardian wanted to treat the patient in another hospital , so the patient was transferred to another hospital .
as the tumor was repeatedly relapsed despite the gtr which was performed twice before , radiation therapy and chemotherapy were performed according to the korean society for pediatric neuro - oncology ( kspno)-s081 protocol , which can be used for a high - grade brain tumor13 ) .
thirty times of fractionated radiation were carried out with 6000 cgy after his third surgery and 4 times of combination chemotherapy with vincristine ( 1.5 mg / m iv push , day 0 , 7 ) , etoposide ( 75 mg / m in normal saline dose 2.5 times iv over 2 hours , day 0 - 4 ) , carboplatin ( 300 mg / m in normal saline 125 ml / m iv over 1 hour , day 0 , 1 ) , and ifosfamide ( 1500 mg / m in dextrose water 200 ml / m with mesna ( 300 mg / m iv over 1 hour , day 0 - 4 ) were applied . the irregular enhancing lesion ( 3.04.0 cm ) was found in a brain mri at six months after the third surgery ( fig .
was found to be smaller than the previous one in the brain mri at thirteen months after the third surgery , this lesion is considered to be the result of radiation injury rather than tumor recurrence ( fig .
he is still alive at 77 months after his first surgery and complaining of mild headache and dizziness , but there are no other neurological abnormalities .
the primary minst is termed as a result of their histological and immunohistochemical similarities to mpnst but is distinguished by their intracerebral location1 ) .
minst is a preferable term to indicate malignant intracerebral schwannoma or neurofibrosarcoma , since these tumors have the appearance of any nerve sheath cells , including schwann cells , perineural fibroblasts , or fibroblasts8,10 ) .
neither our case nor the other previously - published case reports could make an accurate diagnosis before pathologic findings . in imaging studies such as brain computed tomography and mri , it is difficult to discriminate between minst and high grade glioma , because those tumors were intra - axial , homogeneously enhancing and had surrounding edema11 ) .
it is difficult to make an accurate diagnosis of minst by looking ordinary hematoxylin and eosin - stained sections alone .
the differential diagnosis of these tumors includes malignant melanomas with schwann - type differentiation , mixed gliomas with mesenchymal differentiation , intracerebral rhabomyosarcomas , desmoplastic infantile ganglioma , intracerebral meningioma , and solitary fibrous tumor2,16 ) .
however , immunohistochemical analysis has special value both in verifying nerve sheath derivation and malignancy16 ) .
positive s-100 protein may help in differentiating the nerve sheath tumors from the other soft tissue tumors6 ) .
the absence of gfap expression in tumor cells ruled out desmoplastic astrocytoma , gliofibroma , and gliosarcoma , whereas the absence of synaptophysin and neurofilament protein excluded desmoplastic ganglioglioma12 ) . in the reported cases ,
the prognosis of minst is poor2 ) . according to the data in table 1 , survival time was longer when the tumor recurrence was slower .
the recurrence free survival after the initial resection appears an important predictor of the overall survival12 ) . in cases of bruner
et al.4 ) , barnard et al.1 ) , and this case which reported long - term survival , the mitotic activity was rare or moderate rather than high .
it seems that if the mitotic activity is low , the recurrence rate is also low and thus the survival time will increase , although we could not take into account of various factors due to insufficient data caused by few number of reports have been produced to date .
a longer survival time was reported when total resection rather than subtotal resection was carried out3,7,16 ) .
it was considered that radiotherapy contributed to playing a limited role in the management of tumor in the early literature14,15 ) .
however , in the recent literature , radiotherapy showed possible effects on the local control and recurrence2,5 ) , but little on the overall survival in patients with minst1,16 ) . in case of beauchesne
et al.2 ) , systemic chemotherapy with doxorubicin ( 3 courses every month ) was prescribed , with mild benefit for the patient .
however , because of the rarity of this tumor type , there are still few reports published and little available information about the chemotherapy8 ) . in this case
, the kspno - so81 protocol was applied , which is one of protocols to treat a pediatric high grade brain tumor such as medulloblastoma and primitive neuroectodermal tumor .
although appropriate regimen of radiation therapy and chemotherapy are not determined yet2,5,15 ) , it is considered to be useful for the long - term survival of the patient to carry out a surgery , adjuvant radiation , and chemotherapy , as shown in this case .
different from the previous cases , this is the first case that had no evidence of tumor recurrence for 50 months after first surgery , and showed long - term survival for more than 77 months without showing no evidence of tumor recurrence .
although a definitive therapeutic regimen for minst has not yet been established due to the limited number of reported cases , a gtr followed by adjuvant radiotherapy and chemotherapy will be recommended to patients of minst .
 we report a long - term survival case of a primary malignant intracerebral nerve sheath tumor ( minst ) occurring in the right frontal lobe of a 13-year old boy . after the gross total resection ( gtr ) 
 , we have performed radiation therapy but it recurred 50 months after the surgery , so the second gtr was performed . later , second tumor recurrence was found 4 months after the second surgery . 
 subsequently the third gtr , radiotherapy , and chemotherapy were carried out . at present , 
 the patient has been remaining alive for 77 months without evidence of tumor recurrence . 
 according to the previous reports , the primary minst is very rare : there are only 8 cases reported . 
 it is also a fast - growing , invasive tumor with poor outcome . 
 this is the first case that had no recurrence for 50 months after the surgery among the reported cases that had been followed up for more than 5 years . 
 it is supposed that a period of recurrence free survival after gtr and low mitotic activity are associated with the patient 's prognosis . 
 a gtr followed by adjuvant radiation therapy and chemotherapy will be recommended to patients of minst . 