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Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions

Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 6725127, 5 pages https://doi.org/10.1155/2019/6725127 Case Report Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions 1 1 1 1 Takashi Mamiya, Shinji Shimato , Toshihisa Nishizawa, Takashi Yamanouchi, 1 2 3 1 Kojiro Ishikawa, Makoto Ito, Masato Abe, and Kyozo Kato Department of Neurosurgery, Kariya Toyota General Hospital, 5-15 Sumiyoshi-cho, Kariya, Aichi, 448-8505, Japan Department of Pathology, Kariya Toyota General Hospital, 5-15 Sumiyoshi-cho, Kariya, Aichi, 448-8505, Japan Department of Diagnostic Pathology, School of Medicine Fujita Health University, Toyoake, Aichi, Japan Correspondence should be addressed to Shinji Shimato; shinji.shimato@gmail.com Received 29 August 2018; Revised 26 November 2018; Accepted 4 December 2018; Published 6 January 2019 Academic Editor: Didier Frappaz Copyright © 2019 Takashi Mamiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Malignant glioma, the most common malignant primary brain tumor in adults, usually occurs in supratentorial space as a single mass lesion, and cerebellar location and multiple appearance are uncommon. We report a case of a 69-year-old female with three lesions simultaneously found in the cerebellum on magnetic resonance images (MRIs) after suffering from gait disturbance. Two lesions were around 15 mm in size and the other one was observed as a spotty enhancement. Although MRI findings suggested brain metastases, whole body examinations denied any primary malignancies. Biopsy for one lesion in the cerebellum was performed, which resulted in pathological diagnosis of malignant astrocytoma. The lesions were considered multicentric glioma based on MRI definition. The treatment with temozolomide and whole brain radiation was completed. Although the patient was discharged in an independent state with the shrinkage of the tumors, she unexpectedly died following sudden loss of consciousness from an unknown cause one month after discharge. The coincidence of cerebellar location and multicentricity characterized by smallness is quite rare in glioma patients, and such MRI findings might be misleading for the diagnosis. We describe the details of the case and discuss the pathogenesis of this unique presentation of malignant glioma with the literatures. 1. Introduction lesion morphology, mild peritumoral edema, and irregular tumor margins can be helpful, although definite diagnosis Glioma is the most common primary malignant brain tumor required histopathology [8, 9]. comprising approximately 30% of all primary brain tumors In this paper, we report a case of malignant glioma which [1] and usually arises as a single mass lesion. Multiple lesions presented with three lesions in the cerebellum. In particular, are categorized as either multifocal gliomas in which the all lesions were small and considered multicentric based on lesions are connected by T2/FLAIR high signal or multi- MRI definition. The appearance of the lesions could be centric gliomas in which they are not [2, 3]. While 12% to misleading for making diagnosis and treatment strategy. 35% of glioblastomas are multifocal, multicentric glioblasto- We describe the characteristics of the case and discuss the mas are much rarer and only account for 2% to 6% of cases pathogenesis of the unique presentation, thereby providing [4]. The common location of gliomas in adults is the cerebral some insights into multicentric glioma in the cerebellum. hemispheres, and glioma in the cerebellum is infrequent, accounting for 0.6-3.3% of all gliomas [5–7]. Therefore, mul- 2. Case Presentation ticentric glioma evolving in the cerebellum is thought to be quite rare. As for the diagnosis of multiple gliomas, certain A 69-year-old woman, with a history of medication for features on magnetic resonance image (MRI) such as variable hypertension, was referred to our hospital because of gait 2 Case Reports in Oncological Medicine (a) (b) (c) (d) (e) (f) (g) (h) Figure 1: Magnetic resonance images (MRIs) of the patient before biopsy. (a-d) Gd-enhanced T1-weighted images (Gd-T1WI) showing three separate lesions in the cerebellum: the lesion in the left cerebellum near the vermis with relatively regular enhancement (a), the lesion with the similar size in the right cerebellum with ring enhancement (b, arrowhead), and the tiny lesion in right cerebellum located far from two lesions (b, c, d, arrow). T2-weighted images (T2WI) showing peritumoral edema around two lesions (e, f, g), but no edema around the tiny lesion (f, arrow). FLAIR showing no clear connection of the tiny lesion to other two lesions (h, arrow). disturbance. Head MRI revealed three separate lesions in the For molecular genetic characteristics, DNA was extracted cerebellum: the largest lesion of approximately 15 mm in from frozen tumor tissue. IDH gene was analyzed by direct diameter in the left cerebellum near the vermis with relatively sequencing, and allelic status of 1p/19q, EGFR, PDGFA, regular enhancement (Figure 1(a)), the lesion of slightly and PTEN was analyzed by multiplex ligation-dependent smaller size in the right cerebellum with ring enhancement probe amplification (MLPA) method using SALSA MLPA (Figure 1(b)), and the tiny lesion in the upper right cerebel- kit P089 and P105 in accordance with the manufacturer’s lum located far from the two lesions (Figures 1(b)–1(d)). protocol (HRC Holland, Amsterdam, the Netherlands) The smallest lesion was not connected to any other lesions [10]. These analyses revealed that the tumor had no allelic on T2/FLAIR (Figures 1(e)–1(h)). loss of 1p/19q, no mutation of IDH, no loss of PTEN, but We suspected these lesions were metastatic tumors and had the amplification of EGFR and PDGFA. performed thorough examination of whole body, which The treatment with whole skull radiation (60 Gy) resulted in negative for any primary lesions. Because all concomitant with temozolomide was administered and com- lesions were small and debulking surgery was unnecessary, pleted without any major side effects. Although the lesions we decided to perform biopsy surgery targeting at the lesion were enlarged during the treatment (Figures 3(a)–3(c)), the patient was discharged in an independent state; the patient near the vermis. We underwent needle biopsy under the guidance of navigation system, and postoperative course was unexpectedly transferred to our hospital due to sudden was uneventful. Histopathological examination revealed loss of consciousness and was in the state of cardiopulmonary tumor cells with eosinophilic cytoplasm and pleomorphism, arrest on arrival. She died shortly despite all possible proce- which were characterized by dense proliferation and diffuse dures. CT scans taken immediately after her death revealed no apparent changes in the intracranial area including the cer- infiltration in the granular cell layer of the cerebellum (Figure 2(a)). Nuclear pleomorphism and mitotic figures ebellum, thereby denying the correlation of cerebellar glioma were observed, but microvascular proliferation and microne- with her sudden loss of consciousness. Nothing was found in crosis were not detected (Figure 2(b)). Immunohistochemis- the whole body that could explain the causes of her death, try revealed the tumor cells were diffusely positive for glial either. The autopsy was not performed because the consent was not obtained from her family. fibrillary acidic protein (GFAP) (Figure 2(c)) and positive for p53 in large part (Figure 2(d)). In particular, p53 clearly showed infiltrating tumor cells at distant area (Figure 2(e)). 3. Discussion IDH1 and H3K27M were negative. MIB-1 labeling index was 21.3% (Figure 2(f)). These findings were consistent with In this case, malignant glioma should be taken into account WHO grade III anaplastic astrocytoma. as a differential diagnosis because malignant gliomas can be Case Reports in Oncological Medicine 3 200 휇m 100 휇m (a) (b) (c) (d) (e) (f) Figure 2: Photomicrographs displaying pathognomonic histopathological features of malignant glioma. (a) H&E staining showed tumor cells with eosinophilic cytoplasm and pleomorphism characterized by dense proliferation and diffuse infiltration in the granular cell layer. (b) Nuclear pleomorphism and mitotic figures were observed, but no microvascular proliferation and micronecrosis were detected. (c) Immunohistochemical staining showed positivity for GFAP. (d) The majority of the tumor cells are positive for p53. (e) P53 staining also revealed infiltrating tumor cells in the granular layer of the cerebellum away from the area of dense tumor cells. (f) The MIB-1 labeling index was 21.3%. (a) (b) (c) (d) (e) (f) Figure 3: MRIs of the patient after biopsy. (a, b, c) MRIs taken at the midpoint of the treatment with chemoradiotherapy. The enlargement of all lesions and the worsening of the peritumoral edema were observed. (d, e, f) MRIs taken at discharge. Shrinkage of all the tumors and the improvement of the peritumoral edema were observed. 4 Case Reports in Oncological Medicine our knowledge, but it would be an interesting question for multicentric and/or multifocal in the posterior fossa [9, 11]. However, we assumed that metastatic brain tumors would the future, and our report could provide one suggestive data. be the most possible particularly because all lesions were Currently, there are no clear guidelines regarding the optimal management of multiple glioma [8], and the role of small. In the literature, there is one case of multiple cerebellar glioma mimicking brain metastasis reported by Walter et al. surgery remains controversial [7, 8]. In our case, aggressive [12]. In their case, a 69-year-old female case of glioma resection apparently should not be indicated because of the showed three separate lesions in the cerebellum with one location and the size, and biopsy followed by the treatment lesion more than 30 mm in diameter and the other two with temozolomide and radiation would be the most reason- able strategy. While the treatment appeared effective in a lesions smaller than 11 mm in diameter. While they men- tioned that these lesions were initially considered most suspi- short period, the actual prognosis of the glioma in this patient cious to be metastatic brain tumors, two small lesions could remains unknown because of the unexpected death. Multiple be regarded as satellite lesions of the largest lesion, which GBM have been associated with a worse prognosis than soli- are sometimes observed in GBM [13]. On the other hand, tary GBM [8, 15, 16], and the optimal treatment strategy for better prognosis should be pursued for this type of glioma. all lesions in our case were small and appear more confusing for the diagnosis. We presented the characteristics of a rare case of multi- Although we successfully made the pathological diagno- centric glioma in the cerebellum. This report could provide sis for this patient, the procedure for biopsy for this type of some supplemental suggestions for the differential diagnosis small lesions appeared more troublesome than usual and fail- in the patients with small multiple lesions in the cerebellum. The elucidation of the pathogenesis of multiple glioma and ure of sampling tumor tissue could happen. Therefore, the diagnosis as brain metastasis might be justified without the development of the optimal treatment strategy would be pathology in such patients even in the situation with no the important challenges in the future. known primary neoplasm, based on the facts that up to 15% of all patients with brain metastases have no clearly Conflicts of Interest detected primary site [14] and that metastasis from extra- cranial primary tumors is the most common diagnosis The authors declare that there is no conflict of interest associated with intra-axial posterior fossa tumor in adults regarding the publication of this paper. [15, 16]. In that context, the evidence that glioma can occur in the cerebellum with multiple small lesions, shown by this paper for the first time in the literature, poses an important References insight for differential diagnosis, and the necessity of histo- pathological verification should be underscored. [1] K. R. Porter, B. J. McCarthy, S. Freels, Y. Kim, and F. G. Davis, The mechanism of multiple gliomas has been an intrigu- “Prevalence estimates for primary brain tumors in the ing topic and some hypotheses are proposed for explaining United States by age, gender, behavior, and histology,” the multicentricity of glioma [4]. There might have been a Neuro-Oncology, vol. 12, no. 6, pp. 520–527, 2010. spatial continuity between different foci and an underlying [2] U. Batzdorf and N. Malamud, “The problem of multicentric invasion of the whole central nervous system by lower grade gliomas,” Journal of Neurosurgery, vol. 20, pp. 122–136, 1963. cells not visible on the MRI and whose malignant transfor- [3] N. Zamponi, F. Rychlicki, A. Ducati, L. Regnicolo, U. Salvolini, mation would occur at separate points simultaneously. and R. A. Ricciuti, “Multicentric glioma with unusual clinical Another possibility would be that a primary high-grade presentation,” Child's Nervous System, vol. 17, no. 1-2, pp. 101–105, 2001. glioma may spread through cerebrospinal fluid or the white matter tracts to other location [17]. In this regard, while the [4] T. Picart, M. Le Corre, E. Chan-Seng, J. Cochereau, and H. Duffau, “The enigma of multicentric glioblastoma: physio- evidence of malignancy in cerebrospinal fluid was absent in pathogenic hypothesis and discussion about two cases,” British our patient, the specimen from biopsy had an interesting Journal of Neurosurgery, pp. 1–4, 2018. finding that tumor cells were observed sparsely in the area [5] H. Adams, K. L. Chaichana, J. Avendano, B. Liu, S. M. Raza, far from tumor cells (Figure 2(e)). This might suggest that and A. Quinones-Hinojosa, “Adult cerebellar glioblastoma: the tumor cells had a remarkable capacity of migration, understanding survival and prognostic factors using a thereby spreading tumor cells could have happened to form population-based database from 1973 to 2009,” World Neuro- the masses at distant sites. Regarding this point, the subven- surgery, vol. 80, no. 6, pp. e237–e243, 2013. tricular zone harbors cell with proliferative potential and has [6] S. Jeswani, M. Nuno, V. Folkerts, D. Mukherjee, K. L. Black, been described as an area which can result in multiple and and C. G. Patil, “Comparison of survival between cerebellar multicentric GBM, with the expression of metalloproteinase and supratentorial glioblastoma patients: surveillance, epide- and mesenchymal markers [18, 19]. In our patient, the miology, and end results (SEER) analysis,” Neurosurgery, proximity of one lesion to forth ventricle might support vol. 73, no. 2, pp. 240–246, 2013. this possibility. [7] M. J. McGirt, K. L. Chaichana, M. Gathinji et al., “Independent Genetically, the tumor had the amplification of EGFR association of extent of resection with survival in patients with and PDGFA, no loss of PTEN, and no mutation of IDH, malignant brain astrocytoma,” Journal of Neurosurgery, which suggested primary glioblastoma based on the recent vol. 110, no. 1, pp. 156–162, 2009. genetic investigations [20]. The relationship of genetic status [8] W. Hassaneen, N. B. Levine, D. Suki et al., “Multiple cranioto- to multicentricity in glioma has been an unknown topic, to mies in the management of multifocal and multicentric Case Reports in Oncological Medicine 5 glioblastoma. Clinical article,” Journal of Neurosurgery, vol. 114, no. 3, pp. 576–584, 2011. [9] T. Kuroiwa, Y. Numaguchi, M. I. Rothman et al., “Posterior fossa glioblastoma multiforme: MR findings,” AJNR. American Journal of Neuroradiology, vol. 16, no. 3, pp. 583–589, 1995. [10] K. Motomura, A. Natsume, Y. Kishida et al., “Benefits of inter- feron-β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: a multicenter study,” Cancer, vol. 117, no. 8, pp. 1721–1730, 2011. [11] S. Utsuki, H. Oka, Y. Miyajima, C. Kijima, Y. Yasui, and K. Fujii, “Adult cerebellar glioblastoma cases have different characteristics from supratentorial glioblastoma,” Brain Tumor Pathology, vol. 29, no. 2, pp. 87–95, 2012. [12] J. Walter, A. Koch, C. Herbold et al., “Multifocal glioblastoma multiforme in the posterior fossa mimicking cerebral metasta- ses: case presentation and review of the current literature,” Journal of Neurological Surgery Part A: Central European Neurosurgery, vol. 74, Supplement 1, pp. e30–e35, 2013. [13] W. B. Pope, J. Sayre, A. Perlina, J. P. Villablanca, P. S. Mischel, and T. F. Cloughesy, “MR imaging correlates of survival in patients with high-grade gliomas,” AJNR. American Journal of Neuroradiology, vol. 26, no. 10, pp. 2466–2474, 2005. [14] H. J. Han, W. S. Chang, H. H. Jung, Y. G. Park, H. Y. Kim, and J. H. Chang, “Optimal treatment decision for brain metastases of unknown primary origin: the role and timing of radiosur- gery,” Brain Tumor Research and Treatment, vol. 4, no. 2, pp. 107–110, 2016. [15] S. A. Levine, P. E. McKeever, and H. S. Greenberg, “Primary cerebellar glioblastoma multiforme,” Journal of Neuro-Oncology, vol. 5, no. 3, pp. 231–236, 1987. [16] R. Stupp, M. E. Hegi, W. P. Mason et al., “Effects of radiother- apy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a rando- mised phase III study: 5-year analysis of the EORTC-NCIC trial,” The Lancet Oncology, vol. 10, no. 5, pp. 459–466, 2009. [17] J. H. Rees, J. G. Smirniotopoulos, R. V. Jones, and K. Wong, “Glioblastoma multiforme: radiologic-pathologic correlation,” Radiographics, vol. 16, no. 6, pp. 1413–1438, 1996. [18] S. F. Shakur, E. Bit-Ivan, W. G. Watkin, R. T. Merrell, and H. I. Farhat, “Multifocal and multicentric glioblastoma with lepto- meningeal gliomatosis: a case report and review of the litera- ture,” Case Reports in Medicine, vol. 2013, Article ID 132679, 8 pages, 2013. [19] T. N. Showalter, J. Andrel, D. W. Andrews, W. J. Curran Jr., C. Daskalakis, and M. Werner-Wasik, “Multifocal glioblas- toma multiforme: prognostic factors and patterns of progres- sion,” International Journal of Radiation Oncology, Biology, Physics, vol. 69, no. 3, pp. 820–824, 2007. [20] D. N. Louis, H. Ohgaki, O. D. Wiestler et al., WHO Classifica- tion of Tumors of the central Nervous System, IARC Press, Lyon, France, 4th edition, 2016. 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Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions

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Copyright © 2019 Takashi Mamiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 6725127, 5 pages https://doi.org/10.1155/2019/6725127 Case Report Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions 1 1 1 1 Takashi Mamiya, Shinji Shimato , Toshihisa Nishizawa, Takashi Yamanouchi, 1 2 3 1 Kojiro Ishikawa, Makoto Ito, Masato Abe, and Kyozo Kato Department of Neurosurgery, Kariya Toyota General Hospital, 5-15 Sumiyoshi-cho, Kariya, Aichi, 448-8505, Japan Department of Pathology, Kariya Toyota General Hospital, 5-15 Sumiyoshi-cho, Kariya, Aichi, 448-8505, Japan Department of Diagnostic Pathology, School of Medicine Fujita Health University, Toyoake, Aichi, Japan Correspondence should be addressed to Shinji Shimato; shinji.shimato@gmail.com Received 29 August 2018; Revised 26 November 2018; Accepted 4 December 2018; Published 6 January 2019 Academic Editor: Didier Frappaz Copyright © 2019 Takashi Mamiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Malignant glioma, the most common malignant primary brain tumor in adults, usually occurs in supratentorial space as a single mass lesion, and cerebellar location and multiple appearance are uncommon. We report a case of a 69-year-old female with three lesions simultaneously found in the cerebellum on magnetic resonance images (MRIs) after suffering from gait disturbance. Two lesions were around 15 mm in size and the other one was observed as a spotty enhancement. Although MRI findings suggested brain metastases, whole body examinations denied any primary malignancies. Biopsy for one lesion in the cerebellum was performed, which resulted in pathological diagnosis of malignant astrocytoma. The lesions were considered multicentric glioma based on MRI definition. The treatment with temozolomide and whole brain radiation was completed. Although the patient was discharged in an independent state with the shrinkage of the tumors, she unexpectedly died following sudden loss of consciousness from an unknown cause one month after discharge. The coincidence of cerebellar location and multicentricity characterized by smallness is quite rare in glioma patients, and such MRI findings might be misleading for the diagnosis. We describe the details of the case and discuss the pathogenesis of this unique presentation of malignant glioma with the literatures. 1. Introduction lesion morphology, mild peritumoral edema, and irregular tumor margins can be helpful, although definite diagnosis Glioma is the most common primary malignant brain tumor required histopathology [8, 9]. comprising approximately 30% of all primary brain tumors In this paper, we report a case of malignant glioma which [1] and usually arises as a single mass lesion. Multiple lesions presented with three lesions in the cerebellum. In particular, are categorized as either multifocal gliomas in which the all lesions were small and considered multicentric based on lesions are connected by T2/FLAIR high signal or multi- MRI definition. The appearance of the lesions could be centric gliomas in which they are not [2, 3]. While 12% to misleading for making diagnosis and treatment strategy. 35% of glioblastomas are multifocal, multicentric glioblasto- We describe the characteristics of the case and discuss the mas are much rarer and only account for 2% to 6% of cases pathogenesis of the unique presentation, thereby providing [4]. The common location of gliomas in adults is the cerebral some insights into multicentric glioma in the cerebellum. hemispheres, and glioma in the cerebellum is infrequent, accounting for 0.6-3.3% of all gliomas [5–7]. Therefore, mul- 2. Case Presentation ticentric glioma evolving in the cerebellum is thought to be quite rare. As for the diagnosis of multiple gliomas, certain A 69-year-old woman, with a history of medication for features on magnetic resonance image (MRI) such as variable hypertension, was referred to our hospital because of gait 2 Case Reports in Oncological Medicine (a) (b) (c) (d) (e) (f) (g) (h) Figure 1: Magnetic resonance images (MRIs) of the patient before biopsy. (a-d) Gd-enhanced T1-weighted images (Gd-T1WI) showing three separate lesions in the cerebellum: the lesion in the left cerebellum near the vermis with relatively regular enhancement (a), the lesion with the similar size in the right cerebellum with ring enhancement (b, arrowhead), and the tiny lesion in right cerebellum located far from two lesions (b, c, d, arrow). T2-weighted images (T2WI) showing peritumoral edema around two lesions (e, f, g), but no edema around the tiny lesion (f, arrow). FLAIR showing no clear connection of the tiny lesion to other two lesions (h, arrow). disturbance. Head MRI revealed three separate lesions in the For molecular genetic characteristics, DNA was extracted cerebellum: the largest lesion of approximately 15 mm in from frozen tumor tissue. IDH gene was analyzed by direct diameter in the left cerebellum near the vermis with relatively sequencing, and allelic status of 1p/19q, EGFR, PDGFA, regular enhancement (Figure 1(a)), the lesion of slightly and PTEN was analyzed by multiplex ligation-dependent smaller size in the right cerebellum with ring enhancement probe amplification (MLPA) method using SALSA MLPA (Figure 1(b)), and the tiny lesion in the upper right cerebel- kit P089 and P105 in accordance with the manufacturer’s lum located far from the two lesions (Figures 1(b)–1(d)). protocol (HRC Holland, Amsterdam, the Netherlands) The smallest lesion was not connected to any other lesions [10]. These analyses revealed that the tumor had no allelic on T2/FLAIR (Figures 1(e)–1(h)). loss of 1p/19q, no mutation of IDH, no loss of PTEN, but We suspected these lesions were metastatic tumors and had the amplification of EGFR and PDGFA. performed thorough examination of whole body, which The treatment with whole skull radiation (60 Gy) resulted in negative for any primary lesions. Because all concomitant with temozolomide was administered and com- lesions were small and debulking surgery was unnecessary, pleted without any major side effects. Although the lesions we decided to perform biopsy surgery targeting at the lesion were enlarged during the treatment (Figures 3(a)–3(c)), the patient was discharged in an independent state; the patient near the vermis. We underwent needle biopsy under the guidance of navigation system, and postoperative course was unexpectedly transferred to our hospital due to sudden was uneventful. Histopathological examination revealed loss of consciousness and was in the state of cardiopulmonary tumor cells with eosinophilic cytoplasm and pleomorphism, arrest on arrival. She died shortly despite all possible proce- which were characterized by dense proliferation and diffuse dures. CT scans taken immediately after her death revealed no apparent changes in the intracranial area including the cer- infiltration in the granular cell layer of the cerebellum (Figure 2(a)). Nuclear pleomorphism and mitotic figures ebellum, thereby denying the correlation of cerebellar glioma were observed, but microvascular proliferation and microne- with her sudden loss of consciousness. Nothing was found in crosis were not detected (Figure 2(b)). Immunohistochemis- the whole body that could explain the causes of her death, try revealed the tumor cells were diffusely positive for glial either. The autopsy was not performed because the consent was not obtained from her family. fibrillary acidic protein (GFAP) (Figure 2(c)) and positive for p53 in large part (Figure 2(d)). In particular, p53 clearly showed infiltrating tumor cells at distant area (Figure 2(e)). 3. Discussion IDH1 and H3K27M were negative. MIB-1 labeling index was 21.3% (Figure 2(f)). These findings were consistent with In this case, malignant glioma should be taken into account WHO grade III anaplastic astrocytoma. as a differential diagnosis because malignant gliomas can be Case Reports in Oncological Medicine 3 200 휇m 100 휇m (a) (b) (c) (d) (e) (f) Figure 2: Photomicrographs displaying pathognomonic histopathological features of malignant glioma. (a) H&E staining showed tumor cells with eosinophilic cytoplasm and pleomorphism characterized by dense proliferation and diffuse infiltration in the granular cell layer. (b) Nuclear pleomorphism and mitotic figures were observed, but no microvascular proliferation and micronecrosis were detected. (c) Immunohistochemical staining showed positivity for GFAP. (d) The majority of the tumor cells are positive for p53. (e) P53 staining also revealed infiltrating tumor cells in the granular layer of the cerebellum away from the area of dense tumor cells. (f) The MIB-1 labeling index was 21.3%. (a) (b) (c) (d) (e) (f) Figure 3: MRIs of the patient after biopsy. (a, b, c) MRIs taken at the midpoint of the treatment with chemoradiotherapy. The enlargement of all lesions and the worsening of the peritumoral edema were observed. (d, e, f) MRIs taken at discharge. Shrinkage of all the tumors and the improvement of the peritumoral edema were observed. 4 Case Reports in Oncological Medicine our knowledge, but it would be an interesting question for multicentric and/or multifocal in the posterior fossa [9, 11]. However, we assumed that metastatic brain tumors would the future, and our report could provide one suggestive data. be the most possible particularly because all lesions were Currently, there are no clear guidelines regarding the optimal management of multiple glioma [8], and the role of small. In the literature, there is one case of multiple cerebellar glioma mimicking brain metastasis reported by Walter et al. surgery remains controversial [7, 8]. In our case, aggressive [12]. In their case, a 69-year-old female case of glioma resection apparently should not be indicated because of the showed three separate lesions in the cerebellum with one location and the size, and biopsy followed by the treatment lesion more than 30 mm in diameter and the other two with temozolomide and radiation would be the most reason- able strategy. While the treatment appeared effective in a lesions smaller than 11 mm in diameter. While they men- tioned that these lesions were initially considered most suspi- short period, the actual prognosis of the glioma in this patient cious to be metastatic brain tumors, two small lesions could remains unknown because of the unexpected death. Multiple be regarded as satellite lesions of the largest lesion, which GBM have been associated with a worse prognosis than soli- are sometimes observed in GBM [13]. On the other hand, tary GBM [8, 15, 16], and the optimal treatment strategy for better prognosis should be pursued for this type of glioma. all lesions in our case were small and appear more confusing for the diagnosis. We presented the characteristics of a rare case of multi- Although we successfully made the pathological diagno- centric glioma in the cerebellum. This report could provide sis for this patient, the procedure for biopsy for this type of some supplemental suggestions for the differential diagnosis small lesions appeared more troublesome than usual and fail- in the patients with small multiple lesions in the cerebellum. The elucidation of the pathogenesis of multiple glioma and ure of sampling tumor tissue could happen. Therefore, the diagnosis as brain metastasis might be justified without the development of the optimal treatment strategy would be pathology in such patients even in the situation with no the important challenges in the future. known primary neoplasm, based on the facts that up to 15% of all patients with brain metastases have no clearly Conflicts of Interest detected primary site [14] and that metastasis from extra- cranial primary tumors is the most common diagnosis The authors declare that there is no conflict of interest associated with intra-axial posterior fossa tumor in adults regarding the publication of this paper. [15, 16]. In that context, the evidence that glioma can occur in the cerebellum with multiple small lesions, shown by this paper for the first time in the literature, poses an important References insight for differential diagnosis, and the necessity of histo- pathological verification should be underscored. [1] K. R. Porter, B. J. McCarthy, S. Freels, Y. Kim, and F. G. Davis, The mechanism of multiple gliomas has been an intrigu- “Prevalence estimates for primary brain tumors in the ing topic and some hypotheses are proposed for explaining United States by age, gender, behavior, and histology,” the multicentricity of glioma [4]. There might have been a Neuro-Oncology, vol. 12, no. 6, pp. 520–527, 2010. spatial continuity between different foci and an underlying [2] U. Batzdorf and N. Malamud, “The problem of multicentric invasion of the whole central nervous system by lower grade gliomas,” Journal of Neurosurgery, vol. 20, pp. 122–136, 1963. cells not visible on the MRI and whose malignant transfor- [3] N. Zamponi, F. Rychlicki, A. Ducati, L. Regnicolo, U. Salvolini, mation would occur at separate points simultaneously. and R. A. 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