although , the incidence of multicentricglioma accounts nearly 2.5% of all gliomas , mostcases are glioblastoma or anaplastic gliomas .
oligodendroglioma cells are detectablein the cerebrospinal fluid in up to 14% of patients , and we recently treated a case of multiple anaplastic oligodendrogliomas , describe the case in detail and discuss the distinction between  multicentric  and  dissemination via cerebrospinal pathways  and the treatment .
a 72-year - oldman revealed aphasia , abnormal behavior , and rapidly progressivedementia since october 13 , 2009 , and hospitalized in our department on oct .
17 , 2009.magnetic resonance imaging ( mri ) enhanced by contrast media demonstrated multiplebrain tumors in left parietal lobe and left paraventricular region [ figure 1a ] . computed tomography ( ct ) scan showed high density of microbleeding in the left paraventricularregion [ figure 1b ] .
biopsy for the tumor in the left parietal tumor was performed . in the permanent section ,
the hematoxylin and eosin - stained specimen showed that thetissue was composed of cells with clear cytoplasm and with round or irregular nucleushaving dense chromatin ( so called honey comb appearance ) that existed in between highly proliferative vasculature [ figure 2 ] .
the nuclei had pleomorphism and a variety ofsize , a lot of mitosis were observed .
microvascular proliferation and necrotic findingswere also seen . occasionally , calcification deposit and microbleeding were observed.immunocy to chemical study showed positive for glial fibrillary acidic protein , stronglypositive for the olig-2 ( oligodendrocyte lineage genes ) stain .
these findings were compatible for anaplastic oligodendroglioma , so geneticalevaluation was performed , showing loss of heterozygosity ( co - deletions ) in chromosome1p19q .
local brain for the left parietal regionradiotherapy was given to a total dose of 50gy , in34 fractions of 1.5gy daily on weekdays from november to december , 2009 .
at the sametime , temozolomide of 120 mg daily was orally administrated for 42 days .
mri was performed just after these combined chemo- and radiotherapy showed lessening of themass effect in the left parietal tumor , but enlarging the size of the tumor in the left paraventricular region [ figure 3 ] .
we considered that enlargement of the paraventriculartumor was pseudoprogression , as consolidating therapy , temozolomide of 240 mg daily ( 150mg / m2/day ) for 5 days was orally administered for 5 times from february to october 2010 at outpatient clinic . despite of the high levels of promoterhypermethyltransferase ( mgmt ) activity , temozolomide is the first linechemotherapeutic agent against anaplastic oligodendroglioma , so we tried temozolomide . but during those period , cerebellar tumor appeared and graduallyenlarged and hydrocephalus was observed [ figure 4 ] . in october 2010 ,
one cycle of temozolomidevia intravenous administration was performed and lessening of the masseffect was seen , so the patient was transferred to rehabilitation hospital . in the end
ofnovember 2010 , the patient 's consciousness deteriorated because of the enlargement ofthe 4th ventricle tumor , hydrocephalus and abnormality of serum electrolyte .
theconsciousness of the patient recovered for a while by correcting the electrolyte balance , but consciousness level worsened again , and respiration and clinical state wasdeteriorated , and died on january , 2011 .  
( a ) magnetic resonance imaging ( mri ) enhanced by contrast media obtained atthe first hospitalization.multiple brain tumors in the left parietal and leftparaventricular region were observed .
the tissue was composed ofcells with clear cytoplasm and with round or irregular nucleus having dense chromatin ( so called honey comb appearance ) .
hematoxylin and eosinstained specimen , 400 mri after radiotherapy 50gy and temozolomide of 120 mg daily for 42 days .
although , lessening of the mass effect of left parietal tumor was observed , enlargementof the paraventricular tumor was seen , which seemed to be pseudoprogression mri performed about 1 year after initial hospitalization .
salvati m. et al.reported 25 cases with multicentricgliomas , 11 cases aremulticentricglioblastomas , 6 cases are multicentric anaplastic astrocytomas , and othercases are combinations of glioblastomas , anaplastic astrocytomas , and low gradegliomas , and no oligodendrogliomas were found .
solomon etal . stated a clear distinction must be made , in cases of multiple tumors , amongdissemination via cerebrospinal pathways , direct extension across commissures , satellitosis , and true multicentrism .
multicentric tumors are widely separated , arisingin different lobes or hemispheres , which is not readily explained by one of the pathwaysmentioned above.in our case , the 4th ventricle tumor which arose about 1 year afterinitial treatment might have been a metastasis via cerebrospinal fluid , although one ofthe multiple sites can not be dismissed entirely . however , left parietal tumor and lefttrigonal area tumor were found at the same time , and those two tumors were separated , arising in the distinct sites , and were not explained either by the dissemination viacerebrospinal pathways or direct extensions , so we considered those tumors weremulticentric.the pathogenesis of multicentricgliomas is unknown.the most quoted hypothesis is the two - step process reported by willis . in the firststage
a large area of the brain undergoes neoplastic transformation , while in the secondstage one or more foci of tumor proliferation develop within the affected area , givingorigin to separate lesions .
the pathogenesis of multicentricglioma include theembryonal rest theory and the two - stage theory , but zlch pointed out the metastasisvia an unknown pathway .
multicentricgliomas are characterized by rapid progression , which may be related tothe fact that they tend to exhibit malignant features on histology , this fact is also validfor the oligodendrogliomas .
the course of our case from initial diagnosis to death was 1year and 3 months , despite of the combined chemoradiotherapy.in our case , the 4thventricle portion tumor which appeared about one year after the initial treatment andwas not detected in the mri taken at initial hospitalization , might be the metastasis viacerebrospinal fluid , as histological type of malignant oligodendroglioma is a risk factor of cerebrospinal fluid dissemination .
finally , the tumor in the left paraventricular region showed progression even just after the temozolomide treatment , and we presumed it was pseudoprogression , because in the first 6 months of post - chemoradiotherapy period , showed a high incidence of pathologically confirmed pseudoprogression associated with treatment - related necrosiswithout viable tumor cells .
various imaging techniques including mr spectroscopy havebeen studied but neither has been found to be powerful to identify pseudoprogression , and unfortunately , the diagnosis of pseudoprogression still depends on pathologicexamination.the disruption of blood - brain barrier with the resultant observation of an earlyradiologic increase in contrast enhancement at mri , which may falsely mimic trueprogression , and this fact made the treatment of this case more complicated .
 a 72 year - old male hospitalized with aphasia , abnormal behavior , and rapidlyprogressive dementia.magnetic resonance imaging ( mri ) enhanced by contrast media demonstrated multiplebrain tumors in left parietal lobe and left paraventricular region . 
 biopsy was performed , andhistopathological examination and genetical evaluation revealed anaplasticoligodendroglioma . 
 local radiation 50gy was given , and temozolomide via orallyadministered for 42 days . 
 after the chemoradiotherapy , even though the parietal tumorshowed lessening of the size , enlargement of the tumor in the left paraventricularregion was observed , and we considered that phenomenon was pseudoprogression . 
 5courses of temozolomide therapy was added , but cerebellar tumor appeared andenlarged with hydrocephalus , and died 1 year and 3 months after the firsthospitalization . 