gbm diffusely infiltrates the surrounding brain tissue , but does not typically invade blood vessels and rarely spreads outside the central nervous system ( cns ) . metastasis to the outside of the cns was accounted for in only 0.2% cases4 ) . the most common site of extraneural metastasis of the gbm is pleura and the lung10,12 ) . although the exact mechanism of extraneural metastasis has been poorly understood , the lymphatic drainage , the venous system and the adjacent dura and bone have been suggested as the three possible routes of extraneural spread2 ) . interestingly , we experienced a rare case of extraneural metastasis of the gbm , presenting as an unusual neck mass . herein , we report this unusual case , with review of the literature , and we suggest the risk factors of extraneural metastasis . a 46-year - old man was referred to our neurosurgical unit complaining of progressive right hemiparesis . at admission , he was alert and fully oriented . neurological examination revealed right hemiparesis ( grade 3/5 ) . in the past medical history , he had undergone a craniotomy in the left fronto - parietal region for brain tumor 10 years ago in another hospital . although we could not obtain pathological and medical records , he informed that his brain tumor had been diagnosed as low grade glioma , and he had received radiation therapy following craniotomy . magnetic resonance images ( mri ) and computed tomography ( ct ) scan on admission demonstrated a poorly defined heterogenously enhancing mass with extensive peritumoral edema in the left frontal motor cortex ( fig . since the mass was located near the previous craniotomy site , we suggested that this tumor might be related with previously diagnosed glioma . under the presumptive diagnosis of secondary tumor , malignant transformation of a low grade glioma or radiation induced glioblastoma the mri scans taken 2 weeks later showed a remnant mass in the left frontal lobe ( fig . 3 ) . considering his previous history of radiation therapy , we performed gamma knife radiosurgery for the remnant mass , with a marginal dose of 20 gy to the 50% isodose line , followed by 6 cycles of adjuvant chemotherapy with the pcv regimen ( i.e. procarbazine , lomustine , and vincristine ) . three years later , he presented with progressive weakness of the right extremities and dysarthria . 4a ) . surgical resection was done for the mass lesion and the histopathological findings revealed recurrence of the gbm . he remained in a stable condition during the 6 cycles of adjuvant chemotherapy with temozolomide . since then , he underwent craniotomy two more times and shunt procedure for the recurrence of the tumor and hydrocephalus for 30 months . five years after the initial diagnosis , a palpable mass lesion was observed on his left side of the neck . the neck ct with contrast enhancement revealed a 34 cm sized round mass , with peripheral rim enhancement in the left side of the neck ( fig . mass was biopsied and the histopathology indicated a metastatic deposit of the gbm . at that time , his condition , including consciousness and motor function , worsened , and the brain mri noted the progression of the gbm . we performed the surgical resection of the brain tumor and of the neck mass , simultaneously . the pathological specimens were shown with increased cellularity , with blood vessel proliferation and necrosis ( 30% ) . all pathological specimens , from both the brain tumor and the neck mass , were confirmed as gbm ( fig . glioblastoma multiforme is one of the most malignant neoplasms in human beings and the most common primary tumor in the cerebral hemisphere . the incidence accounts for 2 to 3 cases/100000 per year in both europe and north america , and 75% of the patients die within 18 months from diagnosis13 ) . gbm commonly spreads by direct extension and infiltration into the adjacent brain tissue and along the white matter tract . although the tumor is associated with a strong tendency for local invasiveness , the metastatic spread of the gbm outside of the cns is extremely rare . thus , the spread outside the cns occurs with a frequency of only 0.2%4 ) . the reason why the gbm rarely metastasizes is still unclear , but some hypotheses have been proposed . the first hypothesis was suggested on the basis of the short life span of patients . the severe aggressiveness of the gbm results in a very short survival period of patients . the second suggestion has been based on the barrier effect of the basement membrane . in in vitro experiments , the capillary basement membrane played an important role as a physical barrier against migration of the glioma cells into the blood stream in the brain1 ) . as another assumption , the cellular environment of the cns also might be related to the prevention of metastasis of the gbm , because the cns lacks extracellular the matrix components , such as collagen and fibronectin , which are overexpressed only in the hyperplastic blood vessels . through hyaluronic acid and other glycosaminoglycans which are main components of the extracellular spaces although the exact mechanism of extraneural metastasis has been poorly understood , cervio et al.2 ) suggested three possible mechanisms of extraneural spread , as follows : 1 ) the lymphatic cerebrospinal fluid drainage into the extraneural tissue ( despite absence of an identifiable lymphatic system in the cns ) ; 2 ) the venous invasion , either via the leptomeningeal sinuses or via the intracerebral vein ; 3 ) direct invasion through the dura and bone or through tumor cell migration along the ventriculoperitoneal shunts . after the surgical procedure , the tumor cells may access the lymphatic or blood circulation through the damaged blood - brain barrier ( bbb ) . craniotomy with tumor resection is associated with the opening of the brain vessels and can be associated with the spread of tumor cells , as previously demonstrated in the literature15 ) . in the present case , the patient underwent several operations , which might increase the chance of distant metastasis . in the literature , the most common sites of metastases were pleura / lungs , followed by lymph nodes , bones and liver8,11,12 ) . in the report on the extraneural metastases of astrocytoma and glioblastoma , the distribution of metastases was , as follows : 43 ( 59.7% ) lung and pleural , 37 ( 51.4% ) lymph node , 22 ( 30.5% ) bone , 16 ( 22.2% ) liver , 5 heart , 3 adrenal gland , 2 each in the kidneys , diaphragm and mediastinum , and 1 each in the pancreas , the thyroid gland , and the peritoneum11 ) . for establishing the presence of extraneural metastasis , the following 4 criteria should be met16 ) : 1 ) the metastatic lesion must be histologically identified as cns tumor ; 2 ) the clinical history must indicate a cns tumor as the initial neoplasm ; 3 ) a complete autopsy must be performed to exclude the possibility of any other primary tumor ; 4 ) the morphologic features of the primary lesion and of the metastatic lesion must be identical . in this case , the patient fulfilled these criteria . at presentation with extraneural metastasis , this patient developed enlargement of the cervical lymph node . since the patient showed the lymphatic involvement of the gbm as extraneural metastasis , we considered that the main pathway of extraneural metastasis might be the lymphatic spread . the possibility of hematogenous metastasis to the neck should be included , because the patient had undergone multiple craniotomies . although it has been well known that surgery could be a risk factor for the extraneural metastasis of the gbm , surgery is not a prerequisite for the extraneural spread of the primary cns tumor . spontaneous metastases also have been reported in patients who had not experienced previous surgery6 ) . spontaneous spreading of the tumor was attributed to direct invasion in both the vascular and the lymphatic systems . in summary , this patient survived for 6 years after aggressive treatments including surgery for 5 times , radiotherapy and chemotherapy . we suggest that the relatively longer lifespan of this patient might have affected the extraneural metastasis of the gbm . the damage of the cerebral vessels and of the bbb by repeated surgical manipulations could also accelerate the tumor penetration outside of the cns . although the exact mechanism of the extraneural metastasis is not well understood , the gbm can metastasize to extraneural organs . multiple craniotomies and longer survival period of the patient could be considered as risk factors of the extraneural metastasis . this present case provides proof for the possibility of extraneural metastasis of the gbm , especially in patients with longer survival . the neuro - oncologists should pay attention to the systematic survey for extraneural metastasis of the gbm .