International Journal of Neuroscience, 2014; 124(9): 704–706 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0020-7454 print / 1543-5245 online DOI: 10.3109/00207454.2013.877901
CASE REPORT
An enigmatic brainstem posterior fossa ganglioglioma in an adult BaiJing Qin,1 Abdul Kader Tabbara,2 Ivana Delalle,3 James Holsapple,2 and Anna Hohler4 1 2
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3 4
Boston University School of Medicine, Boston, MA, USA Department of Neurosurgery, Boston Medical Center, Boston, MA, USA Department of Pathology, Boston Medical Center, Boston, MA, USA Department of Neurology, Boston Medical Center, Boston, MA, USA Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration. KEYWORDS: gangliogliomatosis, posterior fossa tumor, primary central nervous system neoplasm
Introduction First described in 1930 by Courville, gangliogliomas characteristically contain both dysplastic glial and neuronal components[1]. These tumors are typically low-grade (WHO Grade I), well-circumscribed, slowgrowing solid or cystic supratentorial neoplasms[2]. Gangliogliomas are rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occur in the pediatric population with an incidence of 7.6%[3,4,5]. For supratentorial gangliogliomas, the 10-year survival rate is 85%. Total resection is the preferred method of treatment of gangliogliomas [6]. Partial resection may have a good prognosis with a 5-year survival rate of 78%. The role of radiation therapy has not yet been established, and is reserved Received 24 August 2012; accepted 18 December 2013 Correspondence: Ms BaiJing Qin, Boston Medical Center, Boston, USA. E-mail: [email protected]
704
for recurrent or unresectable gangliogliomas, and adjuvant treatment in subtotally resected gangliogliomas. Due to the slow-growing nature of this neoplasm, the clinical course is indolent with progressive neurological dysfunction evolving over several months to years. The most common presentations include seizures and ataxia from involvement of the temporal lobes and cerebellum, respectively[7]. Other neurological deficits can present depending on tumor location in frontal lobe, pineal gland, basal ganglia, hypothalamic, and optic chiasm gangliogliomas. Gangliogliomas involving the brainstem are extremely rare[8,9]. Brainstem ganglioglioma may present with headache, gait disturbance, ataxia, diplopia, nystagmus, dizziness, syncope, hemiparesis, quadriparesis, cranial nerve dysfunction, hearing loss, facial pain, and swallowing difficulties. We report a case of polynodular and cystic periventricular brainstem and cerebellar ganglioglioma with atypical presentation and features.
Ganglioglioma
705
Int J Neurosci Downloaded from informahealthcare.com by Nyu Medical Center on 05/03/15 For personal use only.
Presentation of Case A 29-year-old female presented to an outside hospital in 2006 for headache, vertigo, and ataxia lasting several months. Her brain imaging showed pontine and cerebellar vermian lesions in the periventricular region. Neurosurgical intervention was planned to obtain a brain biopsy for diagnosis and possible lesion resection. Prior to the surgery, the patient received a trial of steroid treatment and noticed marked improvement in her functioning and gait. The steroids were discontinued at the patient’s request due to side effects of irritability and weight gain. The patient underwent suboccipital craniectomy with biopsy and resection of her brain lesions; the resected area showed nondiagnostic scar tissue. Her ataxia symptoms worsened and she developed seizures. Two years after initial presentation, the patient was referred to our institution. On examination, she had diplopia, saccadic dysfunction, dysarthria, dysmetria, and ataxia. A repeat brain FLAIR MRI showed postoperative changes of cerebellar encephalomalacia and fourth ventricle dilatation (Figure 1A). New hyperintense lesions in the right cerebellar vermis and a right cerebellar peduncle with protrusion into the fourth ventricle. In addition, left pontine and medullary lesions were noted. MRI of the spine was essentially normal. Lumbar puncture was obtained which was negative for infection and specifically sarcoidosis, Lyme disease, multiple sclerosis, syphilis, cryptococcus, Epstein–Barr virus, cytomegalovirus, and cytology were evaluated. Whole body scanning did not reveal any specific focus of neoplasm, inflammation, or infection. Several subsequent brain scans were obtained revealing a fluctuating inflammatory disease with enlarging and shrinking cystic components (Figure 1B). Eventually the patient agreed to another brain biopsy that showed hypercellular white matter with scattered Rosenthal fibers and eosinophilic granular bodies. In addition, large cells with atypical glial nuclei as well as rare binucleated cells were present. Atypical astrocytic nuclei were occasionally highlighted by Olig2-immunohistochemistry. IDH1-immunohistochemistry was negative. MIB-1 labeling index was low as very few Ki-67 immunoreactive nuclei were present. No necrosis or endothelial proliferation was observed. The presence of BRAF V600E mutation was subsequently established. Together, these findings were most consistent with ganglioglioma WHO grade II (Figure 2).
Figure 1. Brain MRI imaging. (A) FLAIR MRI from
the initial evaluation of the patient and after her first brain biopsy reveals signal changes in the left greater than right pons and middle cerebellar peduncles worse on the right. Post-operative changes are noted with distension of the fourth ventricle. (B) Within the next year on FLAIR MRI, the left middle cerebral peduncle reveals a more established cystic component. The right middle cerebral peduncle signal change has also increased.
Discussion An atypical feature in this rare case of brainstem ganglioglioma is its location and appearance. Gangliogliomas typically appear as well-circumscribed, homogenous C
2014 Informa Healthcare USA, Inc.
masses with or without a cystic component that sometimes contains punctate microcalcifications. Gadolinium enhancement of the solid component of the tumor occurs in half of the cases, and the pattern varies from
Int J Neurosci Downloaded from informahealthcare.com by Nyu Medical Center on 05/03/15 For personal use only.
706
BJ. Qin et al.
Figure 2. Cerebellar biopsy specimen. Representative field from the diagnostic frozen section shows several pleomorphic glial nuclei (stars), occasional binucleated cell (arrow), and Rosenthal fibers (arrowhead).
homogenous, to heterogeneous, to ring-enhancing. The pattern of enhancement is usually patchy for infratentorial tumors as opposed to supratentorial gangliogliomas that have an isolated enhancing mass[10]. The rarity of this case is magnified by the radiological evolution of these islands of infiltrating lesions that extended to involve the pons, medulla, and cerebellar vermis and peduncles. Due to the periventricular location of the lesions, we believe that seeding of the fourth ventricle from a primary lesion may have occurred early on in the development of the neoplasm, thus explaining the pattern of diffuse centriventricular involvement. This is a rare case for a number of reasons. First and foremost, the type and location of this tumor in an adult is uncommon. In addition, the fluctuating course of this process, and the difficulty with diagnosis made this a particularly challenging case. A ganglioglioma should be included in the differential diagnosis for a slow growing fluctuating process, which may involve cystic components in the brainstem.
Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Courville CB. Ganglioglioma: tumor of the central nervous system: review of the literature and report of two cases. Arch Neurol Psychiatr 1930;24:439–91. 2. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97–109. 3. Zentner J, Wolf HK, Ostertun B, et al. Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 1994;57:1497–502. 4. Lantos PL, Vandenberg SR, Kleihues P. Tumours of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield’s neuropathology. 6th ed. London: Arnold; 1997:663–77. 5. Blumcke I, Wiestler OD. Gangliogliomas: an intriguing tumor entity associated with focal epilepsies. J Neuropathol Exp Neurol 2002;61:575–84. 6. Baussard B, Di Rocco F, Garnett MR, et al. Pediatric infratentorial gangliogliomas: a retrospective series. J Neurosurg 2007;107:286–91. 7. Castillo M. Gangliogliomas: ubiquitous or not? Am J Neuroradiol 1998;19:807–9. 8. Westwood DA, MacFarlane MR. Pontomedullary ganglioglioma: a rare tumour in an unusual location. J Clin Neurosci 2009;16:108–10. ´ 9. Lagares A, Gomez PA, Lobato RD, Ricoy JR, Ramos A, de la Lama A. Ganglioglioma of the brainstem: report of three cases and review of the literature. Surg Neurol 2001;56:315–22. 10. Provenzale JM, Ali U, Barboriak DP, et al. Comparison of patient age with MR imaging features of gangliogliomas. AJR Am J Roentgenol 2000;174:859–62.
International Journal of Neuroscience
CASE REPORT
An enigmatic brainstem posterior fossa ganglioglioma in an adult BaiJing Qin,1 Abdul Kader Tabbara,2 Ivana Delalle,3 James Holsapple,2 and Anna Hohler4 1 2
Int J Neurosci Downloaded from informahealthcare.com by Nyu Medical Center on 05/03/15 For personal use only.
3 4
Boston University School of Medicine, Boston, MA, USA Department of Neurosurgery, Boston Medical Center, Boston, MA, USA Department of Pathology, Boston Medical Center, Boston, MA, USA Department of Neurology, Boston Medical Center, Boston, MA, USA Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration. KEYWORDS: gangliogliomatosis, posterior fossa tumor, primary central nervous system neoplasm
Introduction First described in 1930 by Courville, gangliogliomas characteristically contain both dysplastic glial and neuronal components[1]. These tumors are typically low-grade (WHO Grade I), well-circumscribed, slowgrowing solid or cystic supratentorial neoplasms[2]. Gangliogliomas are rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occur in the pediatric population with an incidence of 7.6%[3,4,5]. For supratentorial gangliogliomas, the 10-year survival rate is 85%. Total resection is the preferred method of treatment of gangliogliomas [6]. Partial resection may have a good prognosis with a 5-year survival rate of 78%. The role of radiation therapy has not yet been established, and is reserved Received 24 August 2012; accepted 18 December 2013 Correspondence: Ms BaiJing Qin, Boston Medical Center, Boston, USA. E-mail: [email protected]
704
for recurrent or unresectable gangliogliomas, and adjuvant treatment in subtotally resected gangliogliomas. Due to the slow-growing nature of this neoplasm, the clinical course is indolent with progressive neurological dysfunction evolving over several months to years. The most common presentations include seizures and ataxia from involvement of the temporal lobes and cerebellum, respectively[7]. Other neurological deficits can present depending on tumor location in frontal lobe, pineal gland, basal ganglia, hypothalamic, and optic chiasm gangliogliomas. Gangliogliomas involving the brainstem are extremely rare[8,9]. Brainstem ganglioglioma may present with headache, gait disturbance, ataxia, diplopia, nystagmus, dizziness, syncope, hemiparesis, quadriparesis, cranial nerve dysfunction, hearing loss, facial pain, and swallowing difficulties. We report a case of polynodular and cystic periventricular brainstem and cerebellar ganglioglioma with atypical presentation and features.
Ganglioglioma
705
Int J Neurosci Downloaded from informahealthcare.com by Nyu Medical Center on 05/03/15 For personal use only.
Presentation of Case A 29-year-old female presented to an outside hospital in 2006 for headache, vertigo, and ataxia lasting several months. Her brain imaging showed pontine and cerebellar vermian lesions in the periventricular region. Neurosurgical intervention was planned to obtain a brain biopsy for diagnosis and possible lesion resection. Prior to the surgery, the patient received a trial of steroid treatment and noticed marked improvement in her functioning and gait. The steroids were discontinued at the patient’s request due to side effects of irritability and weight gain. The patient underwent suboccipital craniectomy with biopsy and resection of her brain lesions; the resected area showed nondiagnostic scar tissue. Her ataxia symptoms worsened and she developed seizures. Two years after initial presentation, the patient was referred to our institution. On examination, she had diplopia, saccadic dysfunction, dysarthria, dysmetria, and ataxia. A repeat brain FLAIR MRI showed postoperative changes of cerebellar encephalomalacia and fourth ventricle dilatation (Figure 1A). New hyperintense lesions in the right cerebellar vermis and a right cerebellar peduncle with protrusion into the fourth ventricle. In addition, left pontine and medullary lesions were noted. MRI of the spine was essentially normal. Lumbar puncture was obtained which was negative for infection and specifically sarcoidosis, Lyme disease, multiple sclerosis, syphilis, cryptococcus, Epstein–Barr virus, cytomegalovirus, and cytology were evaluated. Whole body scanning did not reveal any specific focus of neoplasm, inflammation, or infection. Several subsequent brain scans were obtained revealing a fluctuating inflammatory disease with enlarging and shrinking cystic components (Figure 1B). Eventually the patient agreed to another brain biopsy that showed hypercellular white matter with scattered Rosenthal fibers and eosinophilic granular bodies. In addition, large cells with atypical glial nuclei as well as rare binucleated cells were present. Atypical astrocytic nuclei were occasionally highlighted by Olig2-immunohistochemistry. IDH1-immunohistochemistry was negative. MIB-1 labeling index was low as very few Ki-67 immunoreactive nuclei were present. No necrosis or endothelial proliferation was observed. The presence of BRAF V600E mutation was subsequently established. Together, these findings were most consistent with ganglioglioma WHO grade II (Figure 2).
Figure 1. Brain MRI imaging. (A) FLAIR MRI from
the initial evaluation of the patient and after her first brain biopsy reveals signal changes in the left greater than right pons and middle cerebellar peduncles worse on the right. Post-operative changes are noted with distension of the fourth ventricle. (B) Within the next year on FLAIR MRI, the left middle cerebral peduncle reveals a more established cystic component. The right middle cerebral peduncle signal change has also increased.
Discussion An atypical feature in this rare case of brainstem ganglioglioma is its location and appearance. Gangliogliomas typically appear as well-circumscribed, homogenous C
2014 Informa Healthcare USA, Inc.
masses with or without a cystic component that sometimes contains punctate microcalcifications. Gadolinium enhancement of the solid component of the tumor occurs in half of the cases, and the pattern varies from
Int J Neurosci Downloaded from informahealthcare.com by Nyu Medical Center on 05/03/15 For personal use only.
706
BJ. Qin et al.
Figure 2. Cerebellar biopsy specimen. Representative field from the diagnostic frozen section shows several pleomorphic glial nuclei (stars), occasional binucleated cell (arrow), and Rosenthal fibers (arrowhead).
homogenous, to heterogeneous, to ring-enhancing. The pattern of enhancement is usually patchy for infratentorial tumors as opposed to supratentorial gangliogliomas that have an isolated enhancing mass[10]. The rarity of this case is magnified by the radiological evolution of these islands of infiltrating lesions that extended to involve the pons, medulla, and cerebellar vermis and peduncles. Due to the periventricular location of the lesions, we believe that seeding of the fourth ventricle from a primary lesion may have occurred early on in the development of the neoplasm, thus explaining the pattern of diffuse centriventricular involvement. This is a rare case for a number of reasons. First and foremost, the type and location of this tumor in an adult is uncommon. In addition, the fluctuating course of this process, and the difficulty with diagnosis made this a particularly challenging case. A ganglioglioma should be included in the differential diagnosis for a slow growing fluctuating process, which may involve cystic components in the brainstem.
Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Courville CB. Ganglioglioma: tumor of the central nervous system: review of the literature and report of two cases. Arch Neurol Psychiatr 1930;24:439–91. 2. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97–109. 3. Zentner J, Wolf HK, Ostertun B, et al. Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 1994;57:1497–502. 4. Lantos PL, Vandenberg SR, Kleihues P. Tumours of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield’s neuropathology. 6th ed. London: Arnold; 1997:663–77. 5. Blumcke I, Wiestler OD. Gangliogliomas: an intriguing tumor entity associated with focal epilepsies. J Neuropathol Exp Neurol 2002;61:575–84. 6. Baussard B, Di Rocco F, Garnett MR, et al. Pediatric infratentorial gangliogliomas: a retrospective series. J Neurosurg 2007;107:286–91. 7. Castillo M. Gangliogliomas: ubiquitous or not? Am J Neuroradiol 1998;19:807–9. 8. Westwood DA, MacFarlane MR. Pontomedullary ganglioglioma: a rare tumour in an unusual location. J Clin Neurosci 2009;16:108–10. ´ 9. Lagares A, Gomez PA, Lobato RD, Ricoy JR, Ramos A, de la Lama A. Ganglioglioma of the brainstem: report of three cases and review of the literature. Surg Neurol 2001;56:315–22. 10. Provenzale JM, Ali U, Barboriak DP, et al. Comparison of patient age with MR imaging features of gangliogliomas. AJR Am J Roentgenol 2000;174:859–62.
International Journal of Neuroscience
