Novel Insights from Clinical Practice Pediatr Neurosurg 2013;49:33–37 DOI: 10.1159/000353992 Received: February 7, 2013 Accepted after Revision: June 24, 2013 Published online: October 29, 2013 Hemorrhagic Ganglioglioma of the Posterior Fossa: Case Report Dhruve S. Jeevan Jayson A. Neil Avinash Mohan Michael Tobias Division of Pediatric Neurosurgery, Department of Neurological Surgery, Maria Fareri Children’s Hospital at Westchester Medical Center, New York Medical College, Valhalla, N.Y., USA Established Facts • Gangliogliomas are tumors of mixed glial cells (astrocytes and oligodendrocytes) together with mature ganglion-type neurons, generally occurring in the supratentorial compartment. Infratentorial gangliogliomas are rare. • Infratentorial gangliogliomas can present in a variety of ways depending on the structures involved. Cranial nerve deficits (e.g. hearing loss, intractable facial pain and hemifacial seizures), hemiparises, cerebellar signs, gait disturbance and headache have all been described. Novel Insights • Hemorrhagic presentation of infratentorial gangliogliomas is extremely rare, but when it does occur, it can have devastating consequences in an otherwise benign disease. • Gangliogliomas are relatively avascular and are rarely necrotic. However, the enhancement pattern of the ganglioglioma may mimic a vascular malformation and, in the presence of hemorrhage, other vascular tumors and arteriovenous malformations should be included in the differential requiring catheter angiography. Key Words Infratentorial ganglioglioma · Posterior fossa · Hemorrhage Abstract Gangliogliomas are rare tumors of the central nervous system that are usually found in the supratentorial compartment, although cases throughout the nervous system have © 2013 S. Karger AG, Basel 1016–2291/13/0491–0033$38.00/0 E-Mail karger@karger.com www.karger.com/pne been described. They are generally low-grade malignancies that are amenable to cure by surgical resection. Most manifest as seizures, though, based on location, they can present with focal neurological deficits. We present here a rare case of an infratentorial ganglioglioma presenting with hemorrhage. To our knowledge this is the only reported case of a hemorrhagic ganglioglioma and, as such, we examine its possible prognosis. © 2013 S. Karger AG, Basel Dhruve S. Jeevan, BMBCH Department of Neurosurgery, New York Medical College Mungar Pavillion, Room 329 Valhalla, N.Y. 10595 (USA) E-Mail dhruve.jeevan @ me.com Introduction Gangliogliomas show a mixed proliferation of glial cells (astrocytes and oligodendrocytes) together with mature ganglion-type neurons, generally occurring in the supratentorial compartment. They are normally benign tumors in which complete excision, when possible, constitutes the optimal treatment leading to disease-free survival. Infratentorial gangliogliomas are rare, with only 30 cerebellar gangliogliomas having been reported in the literature [1–26]. We report on a rare case of cerebellar ganglioglioma presenting acutely with hemorrhage. This is, to the best of our knowledge, the first reported case of hemorrhagic ganglioglioma of the posterior fossa. This case adds to the growing knowledge about this entity, and leads us to question the clinical grading of such lesions. Postoperative Course The postoperative course was uneventful. Immediate postoperative MR imaging did show a small enhancing nodule in the left cerebral hemisphere, which was subsequently resected at 6 months. Pathology confirmed the previous diagnosis of WHO grade I ganglioglioma. At present, 1 year after initial presentation, the patient remains tumor-free with no residual deficits. Discussion Case Report History and Findings A 9-year-old female with a history of intermittent headaches over 2–3 weeks presented to our institution acutely with severe headache, nausea and vomiting, unresponsive to analgesics. On arrival in the emergency room, the patient had become progressively lethargic, only opening her eyes to stimulation, and her speech was limited to 1–2 words when questioned. No cranial nerve deficits, nystagmus or limb ataxia were noted from our limited examination, and it was established that there was no family history of gait disturbance. A cranial computerized tomography (CT) was performed which demonstrated a midline posterior fossa hemorrhage with extension into the fourth and third ventricles with surrounding vasogenic edema, obstructive hydrocephalus and effacement of sulci (fig. 1). A CT angiogram completed at the same time did not show any evidence of underlying arteriovenous malformation or aneurysm. Calcification was seen along the left lateral aspect of the vermian hemorrhage, raising the possibility of an underlying lesion. Due to her deteriorating neurological condition, the patient was intubated and an external ventricular drain was placed. Subsequently, a brain magnetic resonance (MR) imaging study was also obtained revealing an enhancing cerebellar lesion with hemorrhagic material (fig. 2). Operation and Pathology The patient subsequently underwent a median suboccipital craniotomy and decompression of hemorrhagic mass with resection of the lesion. The tumor appeared as a hemorrhagic, firm, grayish vascular mass and had a mixed soft and hard consistency. Neuropathological examination revealed the presence of a tumor with large focus of central hemorrhage walled in by tumor tissue with the presence of ganglion-type neurons in a mixed glial background, WHO grade I (fig. 3). The astrocytic background was found to express glial fibrillary acid protein (GFAP) within the cytoplasm and fibrillary processes, while a group of telangiec- 34 tatic vessels along the periphery, resembling an angioma, bordered the central hemorrhagic zone. The cells showed biphenotypic differentiation with several cells expressing glial fibrillary acid protein within the cytoplasm and fibrillary processes, while scattered large uni- or binucleate ganglionic cells with eccentric nuclei and prominent nucleoli that were immunoreactive of synaptophysin and chromogranin were seen. These ganglionic cells showed dystrophic intracytoplasmic accumulation of phosporylated neurofilament. The features were characteristic of a ganglioglioma with neovascularization causing intratumoral hemorrhage. Pathology was confirmed with outside consultation by two neuropathologists. Pediatr Neurosurg 2013;49:33–37 DOI: 10.1159/000353992 Gangliogliomas of the central nervous system are uncommon and form only 0.4–1.3% of all intracranial neoplasms [26]. Typically, they are supratentorial compartment lesions, with the majority occurring in the temporal lobe, although cases throughout the central nervous system have been described [27]. Peak incidence is between 10 and 20 years of age [28]. Infratentorial gangliogliomas present in a variety of ways depending on the structures involved; cranial nerve deficits (e.g. hearing loss, intractable facial pain and hemifacial seizures), hemiparises, cerebellar signs, gait disturbance and headache have all been described [2, 5, 12, 29– 31]. Interestingly, epilepsy of cerebellar origin has also been reported in patients with cerebellar gangliogliomas [3, 12, 18–20]. In general, cerebellar gangliogliomas are rare, with only 30 cases being reported in the literature [1–26, 31–34], and they usually present with a short history (mean 1.6 years) [35]. To our knowledge, this is the first documented case of a cerebellar ganglioglioma presenting with hemorrhage. Typically, gangliogliomas are thought to be of lowgrade malignancy, grades I–II according to WHO classification. However, anaplastic gangliogliomas have been previously described [36], and are typically due to dedifferentiation of the glial component. It is estimated that <10% of gangliogliomas become anaplastic. Grossly, they are typically intra-axial, firm, grayish lesions, and occasionally have cystic components that are more common in children. Microscopically, they consist Jeevan/Neil/Mohan/Tobias Fig. 1. Axial CT study demonstrating a midline posterior fossa hemorrhage with extension into the fourth and third ventricles, with surrounding vasogenic edema and obstructive hydrocephalus. Color version available online Fig. 2. Axial T1-weighted, T2-weighted and contrast-enhanced T1-weighted MR imaging demonstrates a hemorrhagic posterior fossa mass appearing to arise from the left cerebellar hemisphere. Fig. 3. A mixed proliferation of glial cells (astrocytes and oligodendrocytes) together with mature ganglion-type neurons staining strongly with chromogranin. HE. Hemorrhagic Ganglioglioma of the Posterior Fossa Pediatr Neurosurg 2013;49:33–37 DOI: 10.1159/000353992 35 of an admixture of glial cells, recognized by their large bizarre size, and prominent nucleoli with positive staining for synaptophysin or neurofilament protein, and neurons that dictate the grading and biologic behavior of the tumor. They are relatively avascular, and rarely necrotic, and as such, angiography yields little additional information. However, the enhancement pattern of the ganglioglioma may mimic a vascular malformation, and catheter angiography is required to exclude a vascular malformation. Intraoperatively, these tumors have in fact been found to be extremely vascular [35, 37]. In this case, the numerous telangiectatic vessels (resembling an angioma) seen bordering the hematoma may have been responsible for the hemorrhage. The recommended treatment for gangliogliomas, regardless of location, is surgical resection. Complete resection is generally associated with cure, though subtotal resection has been shown not to significantly alter prognosis. The use of radiation or chemotherapy thereafter is suggested only if the tumor is highly anaplastic and progressive or altogether unresectable. The use of radiation and chemotherapy in children is controversial and is theorized to be a possible cause for malignant degeneration [36, 38]. Generally, these tumors have a benign clinical course. In fact, although often only partial resection is possible with infratentorial gangliogliomas, the overall survival time is not reduced in comparison to superatentorial gangliogliomas where radical resection is feasible [31]. Further, radiographic invasiveness or pathological anaplasia does not correlate with clinical outcome [2, 39]. In general, patients with gangliogliomas, regardless of location, tend to have a good prognosis [39]. Nevertheless, as our case demonstrates, this may not be entirely true. The hemorrhagic presentation in our patient leads us to question the benign nature of these lesions. Conclusion Infratentorial gangliogliomas are rare tumors that usually present with a longstanding history of nonspecific complaints. As in the past, even with partial resection, prognosis remains good. This case clearly demonstrates that these lesions are not always benign in presentation and can present in a malignant fashion with hemorrhagic decompensation. References 1 Bills DC, Hanieh A: Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. J Neurosurg 1991;75:134–137. 2 Blatt GL, Ahuja A, Miller LL, Ostrow PT, Soloniuk DS: Cerebellomedullary ganglioglioma: CT and MR findings. AJNR Am J Neuroradiol 1995;16:790–792. 3 Chae JH, Kim SK, Wang KC, Kim KJ, Hwang YS, Cho BK: Hemifacial seizure of cerebellar ganglioglioma origin: seizure control by tumor resection. Epilepsia 2001;42:1204–1207. 4 Chang T, Teng MM, Lirng JF: Posterior cranial fossa tumours in childhood. Neuroradiology 1993;35:274–278. 5 Dhillon RS: Posterior fossa ganglioglioma – an unusual cause of hearing loss. J Laryngol Otol 1987;101:714–717. 6 Evans AJ, Fayaz I, Cusimano MD, Laperriere N, Bilbao JM: Combined pleomorphic xanthoastrocytoma-ganglioglioma of the cerebellum. Arch Pathol Lab Med 2000;124:1707–1709. 7 Fukuoka T, Tamiya T, Yamanaka A, Furuta T, Moriya Y, Nishimoto A, Tabuchi K: A case of cerebellar ganglioglioma in an infant – immunohistochemical study. No To Shinkei 1985; 37:1101–1107. 8 Garcia CA, McGarry PA, Collada M: Ganglioglioma of the brain stem. Case report. J Neurosurg 1984;60:431–434. 36 9 Geyer JR, Schofield D, Berger M, Milstein J: Differentiation of a primitive neuroectodermal tumor into a benign ganglioglioma. J Neurooncol 1992;14:237–241. 10 Handa H, Yamagami T, Furuta M: An adult patient with cerebellar ganglioglioma. J Neurooncol 1994;18:183–189. 11 Harada K, Sigemori M, Kobayashi S, Matsuo H, Kuramoto S, Aoyagi K: Cerebellar ganglioglioma: a case report. No Shinkei Geka 1988; 16:607–612. 12 Harvey AS, Jayakar P, Duchowny M, Resnick T, Prats A, Altman N, Renfroe JB: Hemifacial seizures and cerebellar ganglioglioma: an epilepsy syndrome of infancy with seizures of cerebellar origin. Ann Neurol 1996;40:91–98. 13 Jay V, Greenberg M: Unusual cerebellar ganglioglioma with marked cytologic atypia. Pediatr Pathol Lab Med 1997;17:105–114. 14 Kimura M, Suzuki M: Cerebellar ganglioglioma: a case report. No Shinkei Geka 1990; 18: 861–865. 15 Kinoshita Y, Kiya K, Satoh H, Sadatomo T, Mizoue T, Tsumura R, Shirozu H, Sugiyama K, Kurisu K: Cerebellar ganglioglioma associated with a huge cyst: case report. No Shinkei Geka 2002;30:503–507. 16 Kwon JW, Kim IO, Cheon JE, Kim WS, Chi JG, Wang KC, Yeon KM: Cerebellopontine Pediatr Neurosurg 2013;49:33–37 DOI: 10.1159/000353992 angle ganglioglioma: MR findings. AJNR Am J Neuroradiol 2001;22:1377–1379. 17 Lindboe CF, Cappelen J, Kepes JJ: Pleomorphic xanthoastrocytoma as a component of a cerebellar ganglioglioma: case report. Neurosurgery 1992;31:353–355. 18 McLone DG, Stieg PE, Scott RM, Barnett F, Barnes PD, Folkerth R: Cerebellar epilepsy. Neurosurgery 1998;42:1106–1111. 19 Mesiwala AH, Kuratani JD, Avellino AM, Roberts TS, Sotero MA, Ellenbogen RG: Focal motor seizures with secondary generalization arising in the cerebellum. Case report and review of the literature. J Neurosurg 2002; 97: 190–196. 20 Mink JW, Caruso PA, Pomeroy SL: Progressive myoclonus in a child with a deep cerebellar mass. Neurology 2003;61:829–831. 21 Mørk SJ, Berg-Jensen M, Haugen A: Cerebellar ganglioglioma. Case report. J Neurosurg 1979;51:562–564. 22 Nishizawa S, Yokoyama T, Ryu H, Ninchoji T, Shimoyama I, Satoh K, Yamamoto S, Uemura K: Cerebellar ganglioglioma – case report. Neurol Med Chir (Tokyo) 1991;31:777– 781. 23 Probst A, Ulrich J, Zdrojewski B, Hirt HR: Cerebellar ganglioglioma in a child. J Neuropathol Exp Neurol 1979;38:57–71. Jeevan/Neil/Mohan/Tobias 24 Turgut M, Ozcan OE: Cerebellar ganglioglioma. Case report. J Neurosurg Sci 1990; 34: 151–153. 25 Wang Z, Sutton LN, Cnaan A, Haselgrove JC, Rorke LB, Zhao H, Bilaniuk LT, Zimmerman RA: Proton MR spectroscopy of pediatric cerebellar tumors. AJNR Am J Neuroradiol 1995; 16:1821–1833. 26 Zentner J, Wolf HK, Ostertun B, Hufnagel A, Campos MG, Solymosi L, Schramm J: Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 1994;57:1497–1502. 27 Koeller KK, Henry JM: From the archives of the AFIP: superficial gliomas: radiologicpathologic correlation. Armed Forces Institute of Pathology. Radiographics 2001; 21: 1533–1556. 28 Demierre B, Stichnoth FA, Hori A, Spoerri O: Intracerebral ganglioglioma. J Neurosurg 1986;65:177–182. Hemorrhagic Ganglioglioma of the Posterior Fossa 29 Epstein N, Epstein F, Allen JC, Aleksic S: Intractable facial pain associated with a ganglioglioma of the cervicomedullary junction: report of a case. Neurosurgery 1982;10:612–616. 30 Friedman WA, Vries JK, Quisling RG: Ganglioglioma of the medulla oblongata. Surg Neurol 1979;12:105–108. 31 Lagares A, Gómez 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: 315–322. 32 Hirose T, Kannuki S, Nishida K, Matsumoto K, Sano T, Hizawa K: Anaplastic ganglioglioma of the brain stem demonstrating active neurosecretory features of neoplastic neuronal cells. Acta Neuropathol 1992;83:365–370. 33 Osanai S, Iida Y, Nomura T, Takahashi F, Tsuji S, Fujiuchi S, Akiba Y, Nakano H, Yahara O, Kikuchi K: A case of unilateral brainstem tumor and impaired ventilatory response. Nihon Kyobu Shikkan Gakkai Zasshi 1994;32:990–995. 34 Vinchon M, Soto-Ares G, Ruchoux MM, Dhellemmes P: Cerebellar gliomas in children with NF1: pathology and surgery. Childs Nerv Syst 2000;16:417–420. 35 Safavi-Abbasi S, Di Rocco F, Chantra K, Feigl GC, El-Shawarby A, Samii A, Samii M: Posterior cranial fossa gangliogliomas. Skull Base 2007;17:253–264. 36 Sasaki A, Hirato J, Nakazato Y, Tamura M, Kadowaki H: Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells. Case report. J Neurosurg 1996; 84: 1055–1059. 37 Baltuch GH, Farmer JP, Meagher-Villemure K, O’Gorman AM, Montes JL: Ganglioglioma presenting as a vascular lesion in a 10-yearold boy. Case report. J Neurosurg 1993; 79: 920–923. 38 Rumana CS, Valadka AB: Radiation therapy and malignant degeneration of benign supratentorial gangliogliomas. Neurosurgery 1998; 42:1038–1043. 39 Lang FF, Epstein FJ, Ransohoff J, Allen JC, Wisoff J, Abbott IR, Miller DC: Central nervous system gangliogliomas. Part 2: clinical outcome. J Neurosurg 1993;79:867–873. Pediatr Neurosurg 2013;49:33–37 DOI: 10.1159/000353992 37 Copyright: S. Karger AG, Basel 2013. 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