Brain Tumor Pathol (2000) 17:41-45 9 The Japan Society of Brain Tumor Pathology 2000 Masao Nakatsuka 9 Shirou Mizuno 9 Tomohiro Kimura Kazuo Hara A case of an unclassified tumor closely resembling dysembryoplastic neuroepithelial tumor with rapid growth Received: June 14, 1999 / Accepted: January 21, 2000 A b s t r a c t We describe a rare case of a tumor resembling dysembryoplastic neuroepithelial tumor. A 3-year-old girl had a generalized convulsion as the initial symptom, without other neurological deficits. Computed tomography showed a hypodense lesion with calcific hyperdensity in the left frontal lobe associated with deformity of the overlying calvarium. Four months later, she had a second seizure, and computed tomographic scan showed that the lesion had increased in size. Subtotal removal of the tumor was performed, and the postoperative course was uneventful without radiation therapy. Histological examination revealed a cortical lesion in which an oligodendrocyte-like area and an astrocyte-like area with cytological atypia were observed. A l t h o u g h the clinical course and the radiological findings closely resembled those of dysembryoplastic neuroepithelial tumor, specific glioneuronal elements were not found histologically. D a u m a s - D u p o r t reported a complex form of dysembryoplastic neuroepithelial tumor that contained glial nodules in addition to a specific glioneuronal element. The histological findings of the glial nodules in this case were quite similar to those she described. We conclude that this Could be an unclassified tumor closely resembling dysembryoplastic neuroepithelial tumor without a specific glioneuronal element. Introduction Dysembryoplastic neuroepithelial tumor (DNT) was first described in 1988 by D a u m a s - D u p o r t et al. 1 According to the World Health Organization ( W H O ) Histologic Typing of Tumours of the Central Nervous System, D N T is a benign supratentorial mixed glial/neuronal neoplasm characterized by an intracortical location, a multinodular architecture, and a heterogeneous cellular composition. 2~3 Patients with D N T usually have intractable seizures without other neurological findings. 4 We report a patient with clinical and radiological features that strongly suggested a diagnosis of D N T , although the tumor was not confirmed to be D N T according to the recent W H O histological classification because of the lack of specific glioneuronal elements. Clinical summary The patient had a normal birth and development without any evidence of phakomatosis. At the age of 3.5 years, she had a generalized seizure. Neurological examination Key words Dysembryoplastic neuroepithelial tumor 9 on admission showed no abnormalities. Computed tomoRapid growth - Cortical lesion Epilepsy 9 Specific graphy (CT) disclosed a fairly well-demarcated hypodense glioneuronal element lesion in the left frontal lobe with calcific hyperdensity and deformity of the overlying calvarium (Fig. la,b). She was treated with anti-epileptic medications and underwent a thorough workup. Four months later, a second generalized M. Nakatsuka - S. Mizuno convulsion occurred. On examination, she had no focal Chita Kousei Hospital, Department of Neurosurgery, Japan neurological deficits, but CT showed that the lesion had T. Kimura grown larger (Fig. lc,d). M R I disclosed a well-demarcated Nagoya City University, Department of Neurosurgery, Japan hypointense area on Tl-weighted images as well as a mixed K. Hara ( ~ ) (hyperintense and isointense) area on T2-weighted images Aichi Medical University Hospital, Division of Pathology, 81-6 Nishitani Kouwa Mihama-chou Chita-gun Aichi-ken 470-2404, Japan (Fig. 2b,c). The cortical lesion resembled a megagyrus that was about 4 c m in diameter and showed heterogeneous Tel. +81-569-82-0395;Fax +81-569-82-4333 central enhancement by gadolinium-DTPA (Fig. 2a). CT This case was registered at the Japan Brain Tumor Reference Center and M R I did not show significant perilesional edema, and (No. 98-012) angiography revealed that the lesion was avascular and had 42 Fig. 1. a,b The initial plain CT shows a calcified lesion in the left frontal lobe. e,d The second plain CT demonstrates that the lesion has grown over a 4-month period Fig. 2. Preoperative MRI. a,d Axial Tl-weighted images obtained after Gd-DTPA administration show a heterogeneously enhanced lesion, b,e Axial Tl-weighted image sh*ows a bypointense lesion, c,f Axial T2-weighted images show a mixed (hyperintense and isointense) intensity lesion 43 caused shifting of the normal structures. Craniotomy was performed to evaluate and treat the lesion. There was no involvement of the overlying skull or dura, and the exophytic lesion on the cortical surface resembled a soft megagyrus (Fig. 3), findings that did not suggest a c o m m o n glioma. Macroscopic total removal of the abnormal gyrus was performed, but postoperative CT demonstrated residual tumor with calcification. After the operation, she had no neurological deficits and no epileptic fits. At 1.5 years after surgery, M R I did not show any regrowth of the lesion (Fig. 4a,b). Pathological findings The cortex contained a solitary nodule (Fig. 5a) with varied cellularity, including an astrocytoma-like area wih small round nuclei, an oligodendrocytoma-like area (Fig. 5b), and undifferentiated cells. Multinucleated giant cells resembling fleurettes were often found (Fig. 5c). In some areas, the cells were arranged in parallel rows, forming a p a t t e r n similar to that of a polar spongioblastoma (Fig. 5d). Calcification (Fig. 5d,e), and necrotic foci were occasionally encountered. Small tumor cells with irregular nuclei were also seen in the mucoid background material along with microcysts (Fig. 5f). However, differentiated neurons or typical specific glioneuronal elements were not observed, and there was no cortical dysplasia. Immunohistologically, the tumor cells were negative for glial fibrillary acidic protein, vimentin, epithelial m e m b r a n e antigen, and cytokeratin. Synaptophysin was faintly positive in the fibrillar matrix, but the cytoplasm of the tumor cells was not stained. In some area, numerous mitotic figures were observed (Fig. 5g), and the MIB-1 (Ki-67 nuclear antigen) staining index in these areas was greater than 10% (Fig. 5h). These findings suggested that the tumor was neuroectodermal in origin and showed minimal glioneuronal differentiation. Discussion Fig. 3. At operation, an exophytic cortical lesion that resembled a megagyrus was detected Fig. 4. MRI 1.5 years after operation: a,b Axial Tl-weighted images and e,d T2-weighted images show no evidence of tumor regrowth In our present patient, the age, symptoms, neurological findings, and good response to surgical treatment suggested a diagnosis of DNT. 1'5 The angiographic avascularity, CT density, M R I intensity, contrast enhancement on CT and MRI, and deformity of the overlying calvarium on CT were also consistent with the radiological features of DNT. 1'5 Moreover, histological examination of this tumor revealed an intracortical lesion showing cellular heterogeneity with 44 Fig. 5. Photomacrograph and photomicrographs of the surgical specimen, a Macroscopic appearance of the resected tumor. Nodular architecture was seen in the cortex and white matter, b The oligodendrocytic components have a typical fried-egg appearance. (X400) c Multinucleared giant cells with eccentric nuclei resemble fleurettes. (• d In some regions, the cells form a polar spon- gioblastic pattern with calcification. (• e Calcification was often found. (• 100) f Small tumor cells with irregular nuclei were seen in the mucoid substance along with microcysts. (• g Mitoses were very common in some areas. (• h MIB-1 immunostaining shows a high labeling index. (;,<200) 45 minimal giioneuronal differentiation. These clinicopathological features all suggested the possibility that the lesion might b e a D N T , although the typical specific glioneuronal e l e m e n t ( S G E ) was not found. 1'5 D a u m a s D u p o r t r e p o r t e d that there are variants of D N T without the usual specific histological features, 5 and there has b e e n a case r e p o r t of D N T without any SGE. 6 However, such opinions have n o t b e e n well supported, because S G E is still generally c o n s i d e r e d essential to define D N T . In D N T , mitoses are rarely encountered, and necrosis is absent or very rare, 1'3'5'7-1zso the lesions r e m a i n stable in size. a's'7's-l~ I m m u n o s t a i n i n g for MIB-1, a m a r k e r of cellular proliferation, was p e r f o r m e d in 18 cases of D N T by D a u m a s - D u p o r t 5 and in 11 cases by Prayson. 3 A m o n g them, only two tumors exhibited a high labeling index, 5 but b o t h lesions r e m a i n e d perfectly stable. It was interesting that our patient's t u m o r increased in size after only 4 months and that it contained loci with a high MIB-1 labeling index. T h e r e have b e e n some other cases where D N T has shown growth, including two patients r e p o r t e d b y Ostern, 4 four patients r e p o r t e d by Prayson, 3 one p a t i e n t r e p o r t e d b y Yamaguchi, H and one p a t i e n t r e p o r t e d by H o n a v a r . 12 However, all of these tumors grew slowly over at least 14 months. If our t u m o r fits into the category of D N T as r e p o r t e d by Ostern, Prayson, Yamaguchi, and H o n a v a r , its growth was the m o s t rapid that has b e e n detected. D e s p i t e its previous r a p i d growth, however, the t u m o r r e m a i n e d stable after surgery, so its clinical course was quite different from that of glioma. Recently, H a n a v a r and co-workers r e p o r t e d that the morphological spectrum of D N T is b r o a d e r than has b e e n previously recognized. Their histological e x a m i n a t i o n of D N T showed a range of features shared by t h r e e subtypes, k n o w n as the multinodular, solitary, and diffuse typesJ 2 If our t u m o r fits any of these categories of D N T , it might be the solitary nodular type. A l l the solitary n o d u l a r tumors r e p o r t e d by H a n a v a r and coworkers were large nodules with a complex form, like classical D N T s J 2 T h e i r solitary n o d u l a r lesions also showed necrosis and a high mitotic index when c o m p a r e d with m u l t i n o d u l a r and diffuse tumors. A l t h o u g h our t u m o r partially r e s e m b l e d their solitary n o d u l a r lesion, H a n a v a r and co-workers emphasized that the essential diagnostic p o i n t was the existence of a mixed cellular c o m p o n e n t , including oligodendroglia-like cells, astrocytes, and m a t u r e neurons. ~2 Therefore, our t u m o r did not fit their definition of solitary D N T , because it lacked any m a t u r e neurons. In accordance with the a c c e p t e d strategy for treating D N T , 5 we have not p e r f o r m e d r e o p e r a t i o n or radiosurgery for the residual tumor, and t h e r e has b e e n no regrowth after 1.5 years. However, careful follow-up will be necessary. In conclusion, this p a t i e n t ' s t u m o r closely r e s e m b l e d a D N T without SGE, although it did not fit exactly into any category of the recent W H O histological classification. Acknowledgments We are grateful to Professor Yoichi Nakazato (Gunma University, Gunma, Japan) for histological advice about this tumor. References 1. Daumaous-Duport C, Scheithauer BW, Chodkieweis JP, et al (1988) Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Neurosurgery 23:545-556 2. Kleihues P, Burger PC, Scheithauer BW (1993) Histological typing of tumours of the central nervous system, 2nd edn. Springer, New York, p 23 3. Prayson RA, Morris HH, Estes ML (1996) Dysembryoplastic neuroepithelial tumor: a clinicopathologic and immunohistochemical study of 11 tumors including MIB 1 immunoreactivity. Clin Neuropathol 15:47-53 4. 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