her medical history included maffucci syndrome with multiple enchondromas of several phalanges and metatarsal bones of the left hand ( fig.1a , b ) , combined with hemangiomas of soft tissue in the right foot ( fig.1c ) . she had skeletal deformities caused by enchondromas of the phalanges of the left fingers , particularly her index finger , appearing at 10  years of age , and hemangiomas on her right foot , appearing at 16  years of age . the left - hand deformities gradually worsened , and she underwent surgical excision of the proximal phalanx of the left index finger and complete removal of the hemangiomas in her right foot at 21  years of age . ( b ) plain x - ray image showing multiple cartilaginous tumors in many phalanges and metacarpal bones of the left hand . ( c ) motor function was almost normal , and her remaining cranial nerve function was otherwise intact . there were no abnormal findings on the laboratory blood tests . computed tomography ( ct ) and mri showed a 40    30-mm mass located in the posterior fossa , which showed a low signal on t1-weighted images ( fig.1e ) and a high signal on t2-weighted images ( fig.1f , g ) . the tumor extended from the middle cerebellar peduncle to the cerebellar vermis , and the intraoperative pathological examination revealed diffuse astrocytoma ; therefore , partial removal was performed to avoid cerebellar ataxia or cerebellar mutism . pathological examination by he staining demonstrated a mild focal increase in cellularity and a lack of vascular proliferation and necrosis within the sampled tissue ( fig.1h ) . the final diagnosis was anaplastic astrocytoma . given the patient 's consent , the relative lack of symptoms and the diffuse nature of the pathology , the patient was administered local radiotherapy with a radiation boost to the residual tumor ( 50  gy in total ) . the patient underwent endoscopic tumor resection , followed by stereotactic radiotherapy ( peripheral dose 2  gy , total 20  gy ) and temozolomide ( tmz ) . tmz was prescribed at a dosage of 150  mg / m / day for 5  days every 28  days , but the patient died at 31  years of age . genomic dna was extracted from formalin - fixed , paraffin - embedded tissue sections extracted by surgery using mightyamp for ffpe ( takara bio , shiga , japan ) according to the manufacturer 's instructions and with the informed consent of the patient . we performed mutation analyses of idh1 , idh2 and tp53 genes ( data s1 ) . we identified the idh2 mutation ( c.516g > t encoding r172s ) in the enchondroma , hemangioma and anaplastic astrocytoma tissues , and the same idh2-r172 mutation was detected in all these tissues ( fig.2a ) . subsequently , the pcr products were subcloned into pcr4-topo vectors , and 14 clones ( enchondroma ) , 17 clones ( hemangioma ) and 69 clones ( astrocytoma ) were sequenced to confirm the idh2-r172s mutations ( data s1 ) . as a result , 28.6% ( 4/14 ) , 11.8% ( 2/17 ) and 2.9% ( 2/69 ) of each tissue , respectively , were shown to carry the idh2-r172s mutation , although these percentages do not necessarily imply those of idh2-r172s - possessing tumor cells ( fig.2b ) . furthermore , missense mutations ( 562c > a encoding l188 m and 1118a > g encoding k373r ) of the tp53 gene were identified in the astrocytoma tissues , but not in the enchondroma or hemangioma tissues ( table1 , fig . ( a ) direct dna sequencing of idh2 was performed in the enchondroma , hemangioma and astrocytoma tissues . ( b ) pcr products of idh2 were subcloned into pcr4-topo vectors , and each clone was sequenced to confirm the heterogeneous mutation of idh2 . we identified the same idh2 ( c.516g > t encoding r172s ) mutation in enchondroma , hemangioma and anaplastic astrocytoma tissues and tp53 mutation in astrocytoma taken from a patient with maffucci syndrome . idh mutations may be a common genetic background in both gliomas and other tumors , and tp53 mutation may have triggered gliomagenesis in our patient with maffucci syndrome . report idh1 mutations in a case of low grade glioma with ollier disease ; however , they did not perform mutation analyses of tp53.9 in contrast , our case suggests that an additional acquired tp53 mutation might induce the malignant transformation in patients with maffucci syndrome . it is interesting to speculate that our patient with maffucci syndrome , who developed an anaplastic astrocytoma and other benign tumors with an idh2 mutation , represents a case of early post - zygotic genetic events , which may have initiated the disease process . appropriate diagnoses of ollier disease and maffucci syndrome are crucial because these diseases are associated with a significant risk of brain tumors , as in our case , and other malignant tumors.10,11 patients with ollier disease and maffucci syndrome have better prognoses if the patients are diagnosed with and treated for malignant tumors in the early stages . recently , we revealed that an anti - idh1/2 monoclonal antibody ( mab , clone msmab-1 ) , which was developed against idh1-r132 g , cross - reacts with idh2-r172s.1214 using msmab-1 , we performed immunohistochemistry against anaplastic astrocytoma tissues . . there might be several problems about the low detection level of idh2-r172s in immunohistochemistry : ( i ) very low sensitivity of msmab-1 ; ( ii ) low frequency of the idh2-r172s expression ; or ( iii ) idh - r172s protein degradation in a paraffin section . although further studies are required to determine the molecular pathogenesis of astrocytic tumors , our case is unique and supports the idh - dependent genetic pathway and second - hit model for gliomagenesis . platform for drug discovery , informatics , and structural life science from the ministry of education , culture , sports , science and technology ( mext ) of japan . regional innovation strategy support program from mext . kakenhi ( 25462242 ) : grant - in - aid for scientific research ( c ) from mext . additional supporting information may be found in the online version of this article : materials and methods . mutational analysis of tp53 . direct dna sequencings of tp53 exon5 ( a ) and exon10 ( b ) were performed in the astrocytoma tissues . immunohistochemical analyses against anaplastic astrocytoma tissues using msmab-1 . mutated idh2-r172s protein expression was determined immunohistochemically in paraffin - embedded tumor specimens . then , they were autoclaved in citrate buffer ( ph 6.0 ; dako ) for 20 min . sections were incubated with 5 g / ml of msmab-1 ( a ) or control ( b ) overnight at 4c , followed by treatment with an lsab kit ( dako ) . color was developed using 3 , 3-diaminobenzidine tetrahydrochloride ( dab ; dako ) for 10 min , and counterstained with hematoxylin .