- Email: [email protected]
High grade glioma in a focal cortical dysplastic lesion
292
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
15. Cervoni L, Artico M, Delfini R. Intraosseous cavernous hemangioma of the skull. Neurosurg Rev 1995;18:61–4. 16. Lobato RD, Lamas E, Amor T, et al. Primary calvarial hemangioma: angiographic study. Surg Neurol 1978;10:389–94. 17. Barnes L. Solitary hemangioma of bone. In: Barnes L, editor. Surgical Pathology of the Head and Neck, Vol. 1. New York: Dekker; 1985. p. 932–6.
18. Gault J, Sarin H, Awadallah NA, et al. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance. Neurosurgery 2004;55:1–17. 19. Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, et al. Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. J Neurosurg 2004;100 (Suppl Pediatrics):481–7.
doi:10.1016/j.jocn.2005.12.007
High grade glioma in a focal cortical dysplastic lesion Wasiq Ahmad Thiryayi
a,*
, Marcia Donaldson-Hugh a, Stuart Ross a, Aruna Chakrabarty
b
a b
Department of Neurosurgery, Leeds General Infirmary, Leeds, UK Department of Histopathology, Leeds General Infirmary, Leeds, UK Received 28 December 2005; accepted 21 February 2006
Abstract A 61-year-old woman presented in 1999 with a recent onset of left-sided focal clonic seizures with associated vague speech arrests. A computerised tomography (CT) scan revealed a hypoattenuated non-enhancing lesion within her right temporal lobe which was biopsied and the histopathological features were reported to be consistent with a hamartoma, reminiscent of tuberous sclerosis. Her seizures remained partially controlled with phenytoin and carbamazepine. She presented again 2 years later with an increase in the frequency of her seizures. A magnetic resonance scan of her brain demonstrated a homogenously enhancing mass lesion in her right temporo-parietal lobe. An initial lobectomy showed a hamartomatous lesion on histology but a subsequent sample obtained from a wide resection carried out when there was further worsening of her condition revealed a grade IV astrocytoma within a focal cortical dysplastic lesion. Our case highlights the importance of considering the possibility of a cortical dysplastic lesion harbouring a malignancy and the need for further research to explore the behaviour of these malformative lesions. 2006 Elsevier Ltd. All rights reserved. Keywords: Focal cortical dysplasia; Cerebral malformations; Malignant transformation; Hamartoma
1. Introduction
2. Clinical presentation
Since the original description by Taylor and Falconer in 1971, focal cortical dysplasia (FCD), the commonest malformation of cortical development characterised by a localised disruption of cerebral cortical architecture with or without the presence of dysmorphic neurons (balloon cells), is being increasingly recognised as a cause of intractable epilepsy in patients of all ages.1,2 Their clinical behaviour has hitherto been considered undeniably benign. We describe the case of a 61-year-old patient with a focal cortical dyplastic lesion who presented with intractable seizures and was subsequently found to have a glioblastoma multiforme within the lesion.
A 61-year-old woman presented to a regional neurosurgical unit with a recent onset of frequent left-sided focal motor seizures. Investigations had identified a lesion within her right temporal lobe which was biopsied and the histopathological features were reported to be consistent with a hamartoma, typical of those seen in tuberous sclerosis. However, she did not possess any of the characteristic cutaneous lesions seen in tuberous sclerosis. There was no family history of this condition and a genetic evaluation did not show either of the classical associated mutations. Her symptoms remained stable with the seizures partially controlled by phenytoin and carbamazepine. During this time, the patient moved to live in another region of the country. Two years later, she presented to our unit with an increase in the frequency of her seizures and a recent onset of leftsided weakness. On neurological examination, there was reduced power and mild hyperreflexia in the left arm and leg. Cranial nerve and fundal examination were normal. An
* Corresponding author. Present address: Department of Neurosurgery, Hope Hospital, 65 Vancouver Quay, Salford Quays, Salford, Manchester, Lancashire M503TU, UK. Tel./fax.: +44 161 8777633. E-mail address: [email protected] (W.A. Thiryayi).
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
Fig. 1. Axial T1-weighted image showing an extensive area of low attenuation in the right hemisphere with effacement of the adjacent lateral ventricle, with a homogenously enhancing mass deep in the right temporoparietal cortex.
MRI of her brain revealed an extensive area of low attenuation in the right frontoparietal, temporal and occipital regions with effacement of the adjacent right lateral ventricle causing extensive midline shift, and a homogenously enhancing mass deep in the right temporoparietal cortex (Fig. 1). Attempts to review her previous cranial images and tissue sections from her biopsy performed 2 years prior to her second presentation were unsuccessful. An urgent right frontotemporal craniotomy was performed and at operation, a temporal lobectomy was done with resection carried out until macroscopically normal brain tissue was identified. The abnormal tissue was noted to have a firm rubbery consistency and frozen section of the resected tissue revealed disorganised and gliotic grey matter with histolopathological examination, once again, showing a pattern consistent with a diagnosis of tuberous sclerosis. Her postoperative course was complicated by fluctuations of her Glasgow Coma Score along with further progression of her left-sided weakness. A CT scan of her brain, 4 days postoperatively, demonstrated persistent areas of patchy low attenuation in the right temporal, frontoparietal and occipital lobes with compression and displacement of the ventricular system to the left (Fig. 2). An MRI done 7 days postoperatively showed enhancement around the margins of the temporal lobectomy site. There was also a much more extensive area of irregular enhancement in the deeper parts of the right temporooccipital region suggesting an area of necrosis (Fig. 3). The appearance was suggestive of a high-grade glioma and in this position, was interpreted as a subependymal
293
Fig. 2. CT scan showing areas of patchy low attenuation in the right temporal, frontoparietal and occipital lobes with compression and displacement of the ventricular system to the left.
Fig. 3. Axial T1-weighted image showing irregular enhancement in the deeper parts of the right temporo-occipital region suggesting an area of necrosis.
giant cell glioma arising around the trigone of the right lateral ventricle. Two weeks after her initial operation she underwent a right partial hemispherectomy, at which time a large bulk
294
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
of the frontal and parietal lobes was removed after identifying grossly abnormal tissue. 3. Histopathology and immunochemistry The specimens obtained from the partial hemispherectomy showed a mixed histological picture. The histology of this lesion showed a neoplasm (mainly in the subcortical area) composed of pleomorphic fibrillary, bipolar or small and plump eosinophilic cells arranged in closely packed sheets (Fig. 4). Mitoses were frequent. The MIB-1 labelling index was 30%. Proliferating and dilated vessels lined by plump endothelial cells were found and the cells were arranged around necrotic areas containing a few macrophages. The lesion extended to the hippocampal formation. The appearances suggested a glioblastoma. The surrounding brain showed a disorganized cortical grey matter with loss of layering, clusters and a dispersed population of pleomorphic, large ballooned, multinucleated glial fibrillary acidic protein (GFAP)-positive astrocytes (Taylor’s balloon cells) suggesting a malformative lesion, and in this instance, focal cortical dysplasia. The lesion showed mild pleomorphism with rare Ki-67 labelling (0.5%). Thus a bimorphic nature of the lesion was demonstrated with a subsequent immunohistochemical analysis showing a common cell of origin.
Post-operatively, she continued to be drowsy but was orientated and had persistent marked left-sided weakness. A plan for post-operative radiotherapy was made and she was discharged back into the community, where she subsequently died. 4. Discussion Malformations of cortical development (MCD) are a spectrum of cerebral developmental lesions characterised by varying combinations of disturbed neuronal migration, abnormal neuronoglial differentiation and cortical organisation. The MCDs are of major clinical significance, generally being associated with severe, refractory epilepsy and developmental delay. The birth prevalence of central nervous system malformations is about 5–10 per 1000 births, with about 40% of the drug-resistant epilepsies in adults and children caused by these malformations.2,3 The disease spectrum includes gross structural malformations, more subtle structural defects and functional brain deficits. Corticogenesis is achieved through a series of ordered temporospatial steps, via the formation of transient structures and successive waves of cell proliferation and migration, followed by cell differentiation and maturation and apoptotic cell death.2 Disruptions of this complex process
Fig. 4. The focal cortical dysplasia lesion. (a) Low power field showing disorganised cortical grey matter with loss of layering. (b) High power field with arrows highlighting large ballooned, multinucleated astrocyte-like cells (Taylor’s cells). (c) Abnormal astrocyte-like cells staining strongly positive for GFAP. (d) Microphotograph of the adjacent high-grade glioma showing pleomorphic fibrillary, bipolar or small and plump eosinophilic cells arranged in sheets (H&E ·400).
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
lead to a wide range of disorders characterised by varying combinations of disturbed neuronal migration, abnormal neuronoglial differentiation and cortical organisation, with the lesions included under the umbrella term of cortical dysplasia. Focal derangements of cortical organisation have been grouped under the term focal cortical dysplasia (FCD) and represent the most common variety of MCD.4,5 Patients with FCD generally have drug-resistant, early onset seizures and magnetic resonance imaging may show focal cortical thickening and simple gyration. In a series of 53 patients with FCD, Kral et al. found that the mean age of onset of seizures was 12.4 years.5 Complete surgical ablation of FCD is accompanied by remission of the seizures in up to 90% of the patients but may be technically difficult.2 The clinical spectrum of FCD in adults is poorly understood. Furthermore, preoperative diagnosis is difficult as it is infrequently demonstrable by CT scanning and not always visualized on MRI.6 Bautista-Jocelyn et al. reported a series of 55 adult patients (aged 17–57 years) with intractable epilepsy and a histopathological diagnosis of FCD.7 Only 24% were diagnosed with FCD pre-operatively and at 12 months follow-up, 65% were found to be seizure-free with 16% showing no significant improvement. In our patient, the initial histopathological examinations had revealed evidence of a cerebral malformative lesion, suggestive of a diagnosis of the forme fruste variant of tuberous sclerosis. Subsequent microscopic and cytoarchitectural evaluation done on tissue samples revealed the true nature of the lesion, an intra-cortical malformation having features typical of FCD, with a co-existent, and most likely co-incidental focus of glioblastoma multiforme within it. The lesions of this form of cortical dysplasia also bear a considerable resemblance to those of the incomplete forms (forme fruste) of tuberous sclerosis. However, the cytoarchitectural abnormalities of cortical tubers without other stigmata of tuberous sclerosis are shown to be distinct from FCD with a characteristic feature of the cortical tubers being the presence of subpial clusters of giant astrocytes and sheaves of astrocytic processes.6 Malignant transformation of cortical dysplastic lesions has been previously cited but is extremely rare.8 This case doi:10.1016/j.jocn.2006.02.020
295
shows a highly unusual occurrence of an FCD with a high grade astrocytoma. It was not possible in this case to determine the relationship between the two lesions but it is most likely that the link was coincidental rather than causal. Furthermore, the case is remarkable in that the initial histopathological examinations revealed a hamartomatous lesion compatible with the diagnosis of the forme fruste variant of tuberous sclerosis, with the subsequent histological and immunochemical analysis revealing the bi-morphic nature of the lesion. 5. Conclusion Our case highlights the importance of a thorough histological and radiological assessment of all cortical lesions. It serves to underscore the remote possibility of a malignancy being harboured by a cortical dysplastic lesion and raises questions regarding the cell of origin of the malignancy. Further research may be needed to investigate the biological behaviour of FCD lesions and to elucidate whether cortical malformative lesions have the potential for neoplastic transformation. References 1. Taylor DC, Falconer MA, Bruton CJ, et al. Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry 1971;34:369–87. 2. Guerrini R, Sicca F, Parmeggiani L. Epilepsy and malformations of the cerebral cortex. Epileptic Disord 2003;5 (Suppl.2):9–26. 3. Bentivoglio M, Tassi L, Pech E, et al. Cortical development and focal cortical dysplasia. Epileptic Disord 2003;5 (Suppl 2):27–34. 4. Honovar M, Meldrum B. Epilepsy. In: Graham D, Lantos P, editors. Greenfield’s Neuropathology. London: Arnold; 1997. p. 936–7. 5. Kral T, Clusmann H, Blumcke I, et al. Outcome of epilepsy surgery in focal cortical dysplasia. J Neurol Neurosurg Psychiatry 2003;74:183–8. 6. Janota I, Polkey CE. Cortical dysplasia in epilepsy. In: Pedley TA, Meldrum BS, editors. Recent Advances in Epilepsy. Edinburgh: Churchill Livingstone; 1992. p. 37–49. 7. Bautista-Jocelyn F, Foldvary SN, Bingaman WE, et al. Focal cortical dysplasia and intractable epilepsy in adults: clinical, EEG, imaging, and surgical features. Epilepsy Res 2003;55:131–6. 8. Hammond RR, Duggal N, Woulfe JM, et al. Malignant transformation of a dysembryoplastic neuroepithelial tumor. J Neurosurg 2002;92:722–5.
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
15. Cervoni L, Artico M, Delfini R. Intraosseous cavernous hemangioma of the skull. Neurosurg Rev 1995;18:61–4. 16. Lobato RD, Lamas E, Amor T, et al. Primary calvarial hemangioma: angiographic study. Surg Neurol 1978;10:389–94. 17. Barnes L. Solitary hemangioma of bone. In: Barnes L, editor. Surgical Pathology of the Head and Neck, Vol. 1. New York: Dekker; 1985. p. 932–6.
18. Gault J, Sarin H, Awadallah NA, et al. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance. Neurosurgery 2004;55:1–17. 19. Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, et al. Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. J Neurosurg 2004;100 (Suppl Pediatrics):481–7.
doi:10.1016/j.jocn.2005.12.007
High grade glioma in a focal cortical dysplastic lesion Wasiq Ahmad Thiryayi
a,*
, Marcia Donaldson-Hugh a, Stuart Ross a, Aruna Chakrabarty
b
a b
Department of Neurosurgery, Leeds General Infirmary, Leeds, UK Department of Histopathology, Leeds General Infirmary, Leeds, UK Received 28 December 2005; accepted 21 February 2006
Abstract A 61-year-old woman presented in 1999 with a recent onset of left-sided focal clonic seizures with associated vague speech arrests. A computerised tomography (CT) scan revealed a hypoattenuated non-enhancing lesion within her right temporal lobe which was biopsied and the histopathological features were reported to be consistent with a hamartoma, reminiscent of tuberous sclerosis. Her seizures remained partially controlled with phenytoin and carbamazepine. She presented again 2 years later with an increase in the frequency of her seizures. A magnetic resonance scan of her brain demonstrated a homogenously enhancing mass lesion in her right temporo-parietal lobe. An initial lobectomy showed a hamartomatous lesion on histology but a subsequent sample obtained from a wide resection carried out when there was further worsening of her condition revealed a grade IV astrocytoma within a focal cortical dysplastic lesion. Our case highlights the importance of considering the possibility of a cortical dysplastic lesion harbouring a malignancy and the need for further research to explore the behaviour of these malformative lesions. 2006 Elsevier Ltd. All rights reserved. Keywords: Focal cortical dysplasia; Cerebral malformations; Malignant transformation; Hamartoma
1. Introduction
2. Clinical presentation
Since the original description by Taylor and Falconer in 1971, focal cortical dysplasia (FCD), the commonest malformation of cortical development characterised by a localised disruption of cerebral cortical architecture with or without the presence of dysmorphic neurons (balloon cells), is being increasingly recognised as a cause of intractable epilepsy in patients of all ages.1,2 Their clinical behaviour has hitherto been considered undeniably benign. We describe the case of a 61-year-old patient with a focal cortical dyplastic lesion who presented with intractable seizures and was subsequently found to have a glioblastoma multiforme within the lesion.
A 61-year-old woman presented to a regional neurosurgical unit with a recent onset of frequent left-sided focal motor seizures. Investigations had identified a lesion within her right temporal lobe which was biopsied and the histopathological features were reported to be consistent with a hamartoma, typical of those seen in tuberous sclerosis. However, she did not possess any of the characteristic cutaneous lesions seen in tuberous sclerosis. There was no family history of this condition and a genetic evaluation did not show either of the classical associated mutations. Her symptoms remained stable with the seizures partially controlled by phenytoin and carbamazepine. During this time, the patient moved to live in another region of the country. Two years later, she presented to our unit with an increase in the frequency of her seizures and a recent onset of leftsided weakness. On neurological examination, there was reduced power and mild hyperreflexia in the left arm and leg. Cranial nerve and fundal examination were normal. An
* Corresponding author. Present address: Department of Neurosurgery, Hope Hospital, 65 Vancouver Quay, Salford Quays, Salford, Manchester, Lancashire M503TU, UK. Tel./fax.: +44 161 8777633. E-mail address: [email protected] (W.A. Thiryayi).
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
Fig. 1. Axial T1-weighted image showing an extensive area of low attenuation in the right hemisphere with effacement of the adjacent lateral ventricle, with a homogenously enhancing mass deep in the right temporoparietal cortex.
MRI of her brain revealed an extensive area of low attenuation in the right frontoparietal, temporal and occipital regions with effacement of the adjacent right lateral ventricle causing extensive midline shift, and a homogenously enhancing mass deep in the right temporoparietal cortex (Fig. 1). Attempts to review her previous cranial images and tissue sections from her biopsy performed 2 years prior to her second presentation were unsuccessful. An urgent right frontotemporal craniotomy was performed and at operation, a temporal lobectomy was done with resection carried out until macroscopically normal brain tissue was identified. The abnormal tissue was noted to have a firm rubbery consistency and frozen section of the resected tissue revealed disorganised and gliotic grey matter with histolopathological examination, once again, showing a pattern consistent with a diagnosis of tuberous sclerosis. Her postoperative course was complicated by fluctuations of her Glasgow Coma Score along with further progression of her left-sided weakness. A CT scan of her brain, 4 days postoperatively, demonstrated persistent areas of patchy low attenuation in the right temporal, frontoparietal and occipital lobes with compression and displacement of the ventricular system to the left (Fig. 2). An MRI done 7 days postoperatively showed enhancement around the margins of the temporal lobectomy site. There was also a much more extensive area of irregular enhancement in the deeper parts of the right temporooccipital region suggesting an area of necrosis (Fig. 3). The appearance was suggestive of a high-grade glioma and in this position, was interpreted as a subependymal
293
Fig. 2. CT scan showing areas of patchy low attenuation in the right temporal, frontoparietal and occipital lobes with compression and displacement of the ventricular system to the left.
Fig. 3. Axial T1-weighted image showing irregular enhancement in the deeper parts of the right temporo-occipital region suggesting an area of necrosis.
giant cell glioma arising around the trigone of the right lateral ventricle. Two weeks after her initial operation she underwent a right partial hemispherectomy, at which time a large bulk
294
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
of the frontal and parietal lobes was removed after identifying grossly abnormal tissue. 3. Histopathology and immunochemistry The specimens obtained from the partial hemispherectomy showed a mixed histological picture. The histology of this lesion showed a neoplasm (mainly in the subcortical area) composed of pleomorphic fibrillary, bipolar or small and plump eosinophilic cells arranged in closely packed sheets (Fig. 4). Mitoses were frequent. The MIB-1 labelling index was 30%. Proliferating and dilated vessels lined by plump endothelial cells were found and the cells were arranged around necrotic areas containing a few macrophages. The lesion extended to the hippocampal formation. The appearances suggested a glioblastoma. The surrounding brain showed a disorganized cortical grey matter with loss of layering, clusters and a dispersed population of pleomorphic, large ballooned, multinucleated glial fibrillary acidic protein (GFAP)-positive astrocytes (Taylor’s balloon cells) suggesting a malformative lesion, and in this instance, focal cortical dysplasia. The lesion showed mild pleomorphism with rare Ki-67 labelling (0.5%). Thus a bimorphic nature of the lesion was demonstrated with a subsequent immunohistochemical analysis showing a common cell of origin.
Post-operatively, she continued to be drowsy but was orientated and had persistent marked left-sided weakness. A plan for post-operative radiotherapy was made and she was discharged back into the community, where she subsequently died. 4. Discussion Malformations of cortical development (MCD) are a spectrum of cerebral developmental lesions characterised by varying combinations of disturbed neuronal migration, abnormal neuronoglial differentiation and cortical organisation. The MCDs are of major clinical significance, generally being associated with severe, refractory epilepsy and developmental delay. The birth prevalence of central nervous system malformations is about 5–10 per 1000 births, with about 40% of the drug-resistant epilepsies in adults and children caused by these malformations.2,3 The disease spectrum includes gross structural malformations, more subtle structural defects and functional brain deficits. Corticogenesis is achieved through a series of ordered temporospatial steps, via the formation of transient structures and successive waves of cell proliferation and migration, followed by cell differentiation and maturation and apoptotic cell death.2 Disruptions of this complex process
Fig. 4. The focal cortical dysplasia lesion. (a) Low power field showing disorganised cortical grey matter with loss of layering. (b) High power field with arrows highlighting large ballooned, multinucleated astrocyte-like cells (Taylor’s cells). (c) Abnormal astrocyte-like cells staining strongly positive for GFAP. (d) Microphotograph of the adjacent high-grade glioma showing pleomorphic fibrillary, bipolar or small and plump eosinophilic cells arranged in sheets (H&E ·400).
Case reports / Journal of Clinical Neuroscience 14 (2007) 292–295
lead to a wide range of disorders characterised by varying combinations of disturbed neuronal migration, abnormal neuronoglial differentiation and cortical organisation, with the lesions included under the umbrella term of cortical dysplasia. Focal derangements of cortical organisation have been grouped under the term focal cortical dysplasia (FCD) and represent the most common variety of MCD.4,5 Patients with FCD generally have drug-resistant, early onset seizures and magnetic resonance imaging may show focal cortical thickening and simple gyration. In a series of 53 patients with FCD, Kral et al. found that the mean age of onset of seizures was 12.4 years.5 Complete surgical ablation of FCD is accompanied by remission of the seizures in up to 90% of the patients but may be technically difficult.2 The clinical spectrum of FCD in adults is poorly understood. Furthermore, preoperative diagnosis is difficult as it is infrequently demonstrable by CT scanning and not always visualized on MRI.6 Bautista-Jocelyn et al. reported a series of 55 adult patients (aged 17–57 years) with intractable epilepsy and a histopathological diagnosis of FCD.7 Only 24% were diagnosed with FCD pre-operatively and at 12 months follow-up, 65% were found to be seizure-free with 16% showing no significant improvement. In our patient, the initial histopathological examinations had revealed evidence of a cerebral malformative lesion, suggestive of a diagnosis of the forme fruste variant of tuberous sclerosis. Subsequent microscopic and cytoarchitectural evaluation done on tissue samples revealed the true nature of the lesion, an intra-cortical malformation having features typical of FCD, with a co-existent, and most likely co-incidental focus of glioblastoma multiforme within it. The lesions of this form of cortical dysplasia also bear a considerable resemblance to those of the incomplete forms (forme fruste) of tuberous sclerosis. However, the cytoarchitectural abnormalities of cortical tubers without other stigmata of tuberous sclerosis are shown to be distinct from FCD with a characteristic feature of the cortical tubers being the presence of subpial clusters of giant astrocytes and sheaves of astrocytic processes.6 Malignant transformation of cortical dysplastic lesions has been previously cited but is extremely rare.8 This case doi:10.1016/j.jocn.2006.02.020
295
shows a highly unusual occurrence of an FCD with a high grade astrocytoma. It was not possible in this case to determine the relationship between the two lesions but it is most likely that the link was coincidental rather than causal. Furthermore, the case is remarkable in that the initial histopathological examinations revealed a hamartomatous lesion compatible with the diagnosis of the forme fruste variant of tuberous sclerosis, with the subsequent histological and immunochemical analysis revealing the bi-morphic nature of the lesion. 5. Conclusion Our case highlights the importance of a thorough histological and radiological assessment of all cortical lesions. It serves to underscore the remote possibility of a malignancy being harboured by a cortical dysplastic lesion and raises questions regarding the cell of origin of the malignancy. Further research may be needed to investigate the biological behaviour of FCD lesions and to elucidate whether cortical malformative lesions have the potential for neoplastic transformation. References 1. Taylor DC, Falconer MA, Bruton CJ, et al. Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry 1971;34:369–87. 2. Guerrini R, Sicca F, Parmeggiani L. Epilepsy and malformations of the cerebral cortex. Epileptic Disord 2003;5 (Suppl.2):9–26. 3. Bentivoglio M, Tassi L, Pech E, et al. Cortical development and focal cortical dysplasia. Epileptic Disord 2003;5 (Suppl 2):27–34. 4. Honovar M, Meldrum B. Epilepsy. In: Graham D, Lantos P, editors. Greenfield’s Neuropathology. London: Arnold; 1997. p. 936–7. 5. Kral T, Clusmann H, Blumcke I, et al. Outcome of epilepsy surgery in focal cortical dysplasia. J Neurol Neurosurg Psychiatry 2003;74:183–8. 6. Janota I, Polkey CE. Cortical dysplasia in epilepsy. In: Pedley TA, Meldrum BS, editors. Recent Advances in Epilepsy. Edinburgh: Churchill Livingstone; 1992. p. 37–49. 7. Bautista-Jocelyn F, Foldvary SN, Bingaman WE, et al. Focal cortical dysplasia and intractable epilepsy in adults: clinical, EEG, imaging, and surgical features. Epilepsy Res 2003;55:131–6. 8. Hammond RR, Duggal N, Woulfe JM, et al. Malignant transformation of a dysembryoplastic neuroepithelial tumor. J Neurosurg 2002;92:722–5.