Subependymoma with Prominent Rosenthal Fiber Formation —Case Report—

Subependymoma With Rosenthal Fibers 933

Neurol Med Chir (Tokyo) 50, 933¿935, 2010

Subependymoma With Prominent Rosenthal Fiber Formation —Case Report—

Tadahiro OHMURA,HitoshiTSUGU, Mitsutoshi IWAASA, Hidetsuna UTSUNOMIYA*,TakeoFUKUSHIMA, and Tooru INOUE

Departments of Neurosurgery and *Radiology, Fukuoka University School of Medicine, Fukuoka

Abstract A 62-year-old woman presented with a rare case of subependymoma associated with prominent Rosen- thal fibers located in the left lateral ventricle manifesting as right hemiparesis and mild motor aphasia. The tumor was well demarcated and consisted of clusters of round nuclei embedded in an abundant gliofibrillary matrix with some microcysts and prominent Rosenthal fibers. Immunohistochemically, the tumor stained positively for glial fibrillary acidic protein and negatively for synaptophysin. This case of subependymoma containing Rosenthal fiber formation is very unusual. Key words: subependymoma, Rosenthal fiber, intraventricular tumor, mixed tumor, glial tumor

Introduction logic feature of widespread distribution of Rosenthal fibers. Subependymoma is a benign intraventricular tumor form- erly called subependymal astrocytoma or subependymal Case Report glomerate astrocytoma, first described in 1945.13) Subependymoma is characterized by glial tumor cell A 62-year-old woman was hospitalized with right hemipa- clusters embedded in an abundant fibrillary matrix with resis and mild motor aphasia. Computed tomography (CT) frequent microcysts and corresponds histologically to performed at the local hospital revealed an oval mass le- grade I in the World Health Organization classification of sion in the left lateral ventricle and a spotty low-density le- brain tumors.6,8) Rosenthal fibers have not been described sion in the left basal ganglia. Focal calcification and cyst as a histopathological feature of this tumor. We treated a formation were apparent (Fig. 1A). The patient was trans- rare case of subependymoma with the peculiar histopatho- ferred to our hospital for further investigation and treat- ment. Her past medical and family histories were both un- Received November 4, 2009; Accepted March 8, 2010 remarkable.

Neurol Med Chir (Tokyo) 50,October,2010 934 T. Ohmura et al.

Fig. 1 A: Computed tomography scan revealing an oval mass lesion with focal calcification and cyst formation in the left lateral ventricle and a spotty low-density lesion in the left basal Fig. 2 Low magnification micrographs of the surgical speci- ganglia. B–D: Magnetic resonance images depicting the tumor men showing clusters of small round nuclei accompanied by as slightly hypointense on the T -weighted image (B) and microcysts, hyalinized vessel, and abundant fibrillary stroma 1 (A), with numerous Rosenthal fibers (B, C), and perivascular hyperintense on the T2-weighted image (C), with partial enhan- cement by gadolinium-diethylenetriamine pentaacetic acid (D). pseudorosettes arranged by Rosenthal fibers (D). Hematoxylin × × E, F: Postoperative axial (E) and coronal (F) T -weighted images and eosin stain, original magnification A and D: 40, B: 20, 1 × with gadolinium showing that almost the entire tumor was re- C: 80. moved.

Neurological examination revealed right hemiparesis moma. In particular, this case was characterized by and mild motor aphasia. Magnetic resonance imaging numerous Rosenthal fibers present in almost 50% of the showed the tumor as slightly hypointense on the T1- tumor (Fig. 2B, C). This background was also compatible weighted image (Fig. 1B) and hyperintense on the T2- with subependymoma. Occasionally, Rosenthal fibers weighted image (Fig. 1C). The tumor was partially en- were oriented around vessels like perivascular pseu- hanced by administration of gadolinium-diethylenetria- dorosettes, but there were few tumor cells (Fig. 2D). mine pentaacetic acid (Fig. 1D). The tumor was 4.5 × 3.5 × 3.5 cm in size. The foramen of Monro was obstructed Discussion by the tumor, and the anterior horn of the left lateral ven- tricle was dilated. Cerebral angiography showed no tumor Subependymoma is a rare, benign tumor originating in the staining. Therefore, we considered the tumor to be ventricular wall, such as that of the septum pellucidum, or subependymoma or central neurocytoma. Subependymo- the floor of the fourth ventricle. These location and radio- ma is difficult to discriminate from other tumors preoper- logical and pathological features require differentiation atively. from central neurocytoma, pilocytic astrocytoma, and Bifrontal craniotomy was performed, and a firm solid ependymoma, all of which frequently incorporate a cystic mass was observed originating from the wall of the left component and/or calcification.5,10) lateral ventricle. The tumor bled easily on suctioning and Histologically, central neurocytoma consists of uniform was subtotally resected through the interhemispheric tran- round cells and includes oligodendroglioma-like features scallosal approach (Fig. 1E, F). Postoperative CT revealed with honeycomb appearance.3) Ependymoma is also asso- communicating hydrocephalus, so ventriculoperitoneal ciated with calcification and cyst formation, but ependy- shunting was also performed. Mild aphasia and hemipare- moma is a moderately cellular glioma consisting of sis remained postoperatively, and the patient was trans- perivascular pseudorosettes and ependymal rosettes.9) ferred to the local hospital for rehabilitation. Pilocytic astrocytoma is frequently located at the The resected tumor was firm, pale, and grayish. Histo- hypothalamus, the thalamus, and the brainstem, but is logical examination showed clusters of round nuclei ac- rarely seen in the lateral ventricle, and exhibits an often companied by microcysts and abundant fibrillary stroma. biphasic pattern with varying proportions of compacted The tumor was well circumscribed with no mitoses or bipolar cells with Rosenthal fibers.14) Among 83 cases of necrosis (Fig. 2A). MIB-1 labeling indices were below 1%. subependymomas, 18% exhibited a mixed histological pat- Immunohistochemical examination was positive for glial tern, and the most common mixture was subependymoma fibrillary acidic protein (GFAP), partially weak positive for and ependymoma.12) epithelial membrane antigen, but negative for synaptophy- In our case, the tumor consisted of clusters of round or sin. These histological findings correspond to subependy- oval shaped nuclei embedded in an abundant gliofibrillary

Neurol Med Chir (Tokyo) 50, October, 2010 Subependymoma With Rosenthal Fibers 935 matrix with some microcystic changes. These features are 106–109 compatible with subependymoma. Although Rosenthal 4) Herndon RM, Rubinstein LJ, Freeman JM, Mathieson G: fibers were present in almost 50% of the tumor, the back- Light and electron microscopic observations on Rosenthal ground is also compatible with subependymoma. There- fibers in Alexander's disease and in multiple sclerosis. JNeu- fore, we considered the tumor to be subependymoma with ropathol Exp Neurol 29: 524–551, 1970 5) Jelinek J, Smirniotopoulos JG, Parisi JE, Kanzer M: Lateral prominent Rosenthal fiber formation, not mixed tumor. ventricular neoplasms of the brain: Differential diagnosis This case of subependymoma containing Rosenthal fiber based on clinical, CT, and MR findings. AJNR Am J Neu- formation is very unusual. roradiol 11: 567–574, 1990 Most commonly, Rosenthal fibers occur as focal 6) Kobayasi N, Toyota M: [Subependymoma]. Rinsho Gazou 14: phenomena in astrocytomas, ependymomas, and multiple 44–45, 1998 (Japanese) sclerosis, and in areas of longstanding gliosis. Rosenthal 7) LoweJ,MorrellK,LennoxG,LandonM,MayerRJ:Rosen- fibers are also detected in lesions treated with vincristine thal fibres are based on the ubiquitination of glial filaments. and radiotherapy.15) Rosenthal fiber formation is suggest- Neuropathol Appl Neurobiol 15: 45–53, 1989 ed to be related to ubiquitin. The cell stress-associated pro- 8)McLendonRE,SchifferD,RosenblumMK,WiestlerOD: tein ubiquitin is localized around the periphery of Rosen- Subependymoma, in Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds): WHO Classification of Tumours of the thal fibers but not in the amorphous central areas, and the Central Nervous System. Lyon, International Agency for ubiquitin-positive regions correspond to the im- Research on Cancer, 2007, pp 70–71 7) munocytochemical localization of GFAP. Electron 9) McLendon RE, Wiestler OD, Kros JM, Korshunov A, Ng HK: microscopy showed variation in the structural pattern of Ependymoma, in Louis DN, Ohgaki H, Wiestler OD, Rosenthal fibers in 8 cases of low grade astrocytoma and Cavenee WK (eds): WHO Classification of Tumours of the reactive gliosis.2) Some Rosenthal fibers contained large Central Nervous System. Lyon, International Agency for amounts of glial filaments intermingled with Rosenthal Research on Cancer, 2007, pp 74–78 fibers and others contained a large amount of electron 10) Nishio S, Morioka T, Suzuki S, Mihara F, Fukui M: [Neuro- dense material and less glial filaments. Therefore, Rosen- imaging features of intraventricular neurocytoma]. No To thal fiber formation is possibly a two-stage process, start- Shinkei 52: 237–241, 2000 (Japanese) 11) Riggs JE, Schochet SS Jr, Nelson J: Asymptomatic adult ing with excessive accumulation of glial filaments within Alexander's disease: entity or nosological misconception? astrocytic processes followed by gradual alteration into Neurology 38: 152–154, 1988 electron-dense amorphous material under the influence of 12) Rushing EJ, Cooper PB, Quezado M, Begnami M, Crespo A, some unknown metabolic or other factors.2) Rosenthal Smirniotopoulos JG, Ecklund J, Olsen C, Santi M: Subepen- fibers may occur due to glial dysfunction caused by a vari- dymoma revisited: clinicopathological evaluation of 83 ety of insults, and have also been described following cases. J Neurooncol 85: 297–305, 2007 prolonged systemic disease.1,4,11,15) Our patient had 13) Scheinker IM: Subependymoma: a newly recognized tumor suffered cerebral infarction, but she had experienced no of subependymal derivation. J Neurosurg 2: 232–240, 1945 systemic diseases. 14) Scheithauer BW, Hawkins C, Tihan T, VandenBerg SR, Burger PC: Pilocytic astrocytoma, in Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds): WHO Classification of References Tumours of the Central Nervous System. Lyon, International Agency for Research on Cancer, 2007, pp 14–21 1) Borrett D, Becker LE: Alexander's disease. A disease of as- 15) Wilson SP, Al-Sarraj S, Bridges LR: Rosenthal fiber en- trocytes. Brain 108: 367–385, 1985 cephalopathy presenting with demyelination and Rosenthal 2) Dinda AK, Sarkar C, Roy S: Rosenthal fibres: an immuno- fibers in a solvent abuser: adult Alexander's disease? Clin histochemical, ultrastructural and immunoelectron Neuropathol 15: 13–16, 1996 microscopic study. Acta Neuropathol 79: 456–460, 1990 3) Figarella-Branger D, Soeylemezoglu F, Burger PC: Central neurocytoma and extraventricular neurocytoma, in Louis Address reprint requests to: Tadahiro Ohmura, M.D., Department DN,OhgakiH,WiestlerOD,CaveneeWK(eds): WHO Clas- of Neurosurgery, Fukuoka University School of Medicine, sification of Tumours of the Central Nervous System.Lyon, 7–45–1 Nanakuma, Johnan–ku, Fukuoka 814–0180, Japan. International Agency for Research on Cancer, 2007, pp

Neurol Med Chir (Tokyo) 50,October,2010