1 2010 Vol: 23(8):1097-1103. DOI: 10.1038/modpathol.2010.94

Coexistent pathology in chronic epilepsy patients with neoplasms

Neoplasms are a well-established cause of medically intractable or chronic epilepsy. Certain tumors, including gangliogliomas and dysembryoplastic neuroepithelial tumors, are well known to be associated with cortical dysplasia. This study retrospectively examines the incidence of coexistent pathology in patients with tumors and chronic epilepsy. This study is a retrospective review of 270 tumors arising in patients with medically intractable epilepsy encountered during a 20-year period (1989–2009). Coexistent pathology was noted in 50 of 270 (17.8%) patients, including 27 males (54%) with a mean age at surgery of 18 years (range 1–52 years). The vast majority of lesions (n=40) (80%) were located in the temporal lobe and less commonly in the parietal lobe (n=4) and the occipital lobe (n=3). Tumor diagnoses included ganglioglioma (n=29), dysembryoplastic neuroepithelial tumor (n=10), low-grade glial/glioneuronal neoplasm (n=5), low-grade astrocytoma (n=2), angiocentric glioma (n=1), low-grade mixed glioma (n=1), dysembryoplastic neuroepithelial tumor/ganglioglioma mixed tumor (n=1), and meningioangiomatosis (n=1). Forty-one (82%) tumors represented WHO grade-I neoplasms. Concomitant pathology included malformation of cortical development (cortical dysplasia) in 40 patients (80%) (Palmini et al type-I: n=37; Palmini et al type-II: n=3). Hamartias were identified in 10 patients (20%), hippocampal sclerosis in four patients (8%), and nodular heterotopia in one patient (2%). The true incidence of coexistent pathology (17.8% in this study) was likely underrepresented, given the limited extent of adjacent non-tumoral tissue sampling in cases of resected tumor. Coexistent pathology may account for the incidence of recurrent or residual epilepsy in patients who undergo tumor resection.

Mentions
Figures
Figure 1: A low-magnification appearance of a temporal lobe resection in a patient diagnosed with a dysembryoplastic neuroepithelial tumor illustrating the relationship between tumor (1B, box) and adjacent malformation of cortical development (1C, box) (hematoxylin and eosin, original magnification × 20). (b) A high-magnification appearance of the box area in 1B showing a dysembryoplastic neuroepithelial tumor characterized by a microcystic background and cells with rounded nuclei (resembling oligodendrocytes) with interspersed normal-appearing neurons (hematoxylin and eosin; original magnification × 200). (c) A higher magnification appearance of the box area in 1C showing a disordered cortical architecture indicated by absence of cortical layer 2 (type-I pattern) (hematoxylin and eosin; original magnification × 200). Figure 2: Angiocentric gliomas are marked by proliferation of elongated glial cells around blood vessels, forming a perivascular pseudo-rosetted structure (hematoxylin and eosin; original magnification × 200). Figure 3: Perivascular proliferations of meningothelial cells characterize meningioangiomatosis (hematoxylin and eosin; original magnification × 200). Figure 4: A type-II malformation of cortical development seen adjacent to a dysembryoplastic neuroepithelial tumor and marked by neuronal cytomegaly (arrows) and balloon cells (arrowheads) (hematoxylin and eosin; original magnification × 200). Figure 5: Hamartia adjacent to a ganglioglioma and characterized by aggregates of small neurons (hematoxylin and eosin; original magnification × 200).
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References
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    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
    • . . . If one examines the larger series that has been reported, gangliogliomas, dysembryoplastic neuroepithelial tumors, and low-grade astrocytomas are the most commonly encountered neoplasms.1, 2, 3, 4, 5, 6 In general, these tumors tend to present earlier in life, frequently in childhood, and generally represent low-grade lesions (WHO grade-I or II tumors) . . .
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    • . . . If one examines the larger series that has been reported, gangliogliomas, dysembryoplastic neuroepithelial tumors, and low-grade astrocytomas are the most commonly encountered neoplasms.1, 2, 3, 4, 5, 6 In general, these tumors tend to present earlier in life, frequently in childhood, and generally represent low-grade lesions (WHO grade-I or II tumors) . . .
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    • . . . If one examines the larger series that has been reported, gangliogliomas, dysembryoplastic neuroepithelial tumors, and low-grade astrocytomas are the most commonly encountered neoplasms.1, 2, 3, 4, 5, 6 In general, these tumors tend to present earlier in life, frequently in childhood, and generally represent low-grade lesions (WHO grade-I or II tumors) . . .
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    • . . . If one examines the larger series that has been reported, gangliogliomas, dysembryoplastic neuroepithelial tumors, and low-grade astrocytomas are the most commonly encountered neoplasms.1, 2, 3, 4, 5, 6 In general, these tumors tend to present earlier in life, frequently in childhood, and generally represent low-grade lesions (WHO grade-I or II tumors) . . .
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    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
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    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  9. Plate KH, Wieser HG, Yasargil MG, et al. Neuropathological findings in 224 patients with temporal lobe epilepsy. Acta Neuropathol 1993;86:433-438 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  10. Wolf HK, Campos MG, Zentner J, et al. Surgical pathology of temporal lobe epilepsy. Experience with 216 cases. J Neuropathol Exp Neurol 1993;52:499-506 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  11. Li LM, Cendes F, Watson C, et al. Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome. Neurology 1997;48:437-444 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  12. Cendes F, Cook JM, Watson C, et al. Frequency and characteristics of dual pathology in patients with lesional epilepsy. Neurology 1995;45:2058-2064 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  13. Li M, Cendes F, Andermann F, et al. Surgical outcome in patient with epilepsy and dual pathology. Brain 1999;122:799-805 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  14. Fauser S, Schulze-Bonhage A, Honegar J, et al. Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology. Brain 2004;127:2406-2418 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  15. Fried I, Kim JH, Spencer DD. Hippocampal pathology in patients with intractable seizures and temporal lobe masses. J Neurosurg 1992;76:735-740 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
  16. Prayson RA, Estes ML, Morris HH. Coexistence of neoplasia and cortical dysplasia in patients presenting with seizures. Epilepsia 1993;34:609-615 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  17. Prayson RA, Khajavi K, Comair YG. Cortical architectural abnormalities and MIB-1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors. J Neuropathol Exp Neurol 1994;54:513-520 , .
  18. Wolf HK, Müller MB, Spänle M, et al. Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol 1994;88:166-173 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
    • . . . Key to the diagnosis of dysembryoplastic neuroepithelial tumor is recognition of the predominant cortical location of the neoplasm and multi-nodular architecture.19, 21 All five of these cases in the current series showed evidence of a coexistent malformation of cortical development; this would suggest that these lesions are perhaps more likely glioneuronal tumors than real gliomas.17, 18, 19, 20, 21 . . .
  19. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. Dysembryoplastic neuroepithelial tumor: a surgically curable tumour of young patients with intractable partial seizures. Neurosurgery 1988;23:545-556 , .
    • . . . A number of series have examined the incidence of various tumor types encountered in the setting of medically intractable epilepsy.1, 2, 3, 4, 5, 6 The prevalence of tumors in this setting has ranged from 12.6 to 56.3%.7, 8, 9, 10 In a subset of these tumors, which are generally low-grade glial or glioneuronal neoplasms, multiple pathologies, which potentially may contribute to the genesis of these seizures, are identifiable (dual pathology).11, 12, 13, 14, 15, 16 Among these, there is a well-established association of certain neoplasms with malformations of cortical development (cortical dysplasia), particularly dysembryoplastic neuroepithelial tumors and gangliogliomas.17, 18, 19, 20 . . .
    • . . . Key to the diagnosis of dysembryoplastic neuroepithelial tumor is recognition of the predominant cortical location of the neoplasm and multi-nodular architecture.19, 21 All five of these cases in the current series showed evidence of a coexistent malformation of cortical development; this would suggest that these lesions are perhaps more likely glioneuronal tumors than real gliomas.17, 18, 19, 20, 21 . . .
  20. Daumas-Duport C. Dysembryoplastic neuroepithelial tumours. Brain Pathol 1993;3:283-295 , .
  21. Louis DN, Ohgaki H, Wiestler OD, et al. (eds) WHO Classification of Tumours of the Central Nervous System. IARC Press: Lyon, FR, 2007 , .
    • . . . Tumor classification was based on the most recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System published in 2007.21 In many cases, there was limited tissue adjacent to the tumor available for examination and evaluation of coexistent pathology was not possible . . .
    • . . . Sometimes, the presence of other pathologic findings, such as prominent perivascular lymphocytes or eosinophilic granular bodies, suggests a ganglioglioma diagnosis in the absence of ganglion cells; the findings are typically not salient features of the typical diffuse or fibrillary low-grade astrocytoma.17, 21 Similarly, on a limited biopsy, the areas of a dysembryoplastic neuroepithelial tumor may resemble an infiltrating low-grade microcystic oligodendroglioma . . .
  22. Palmini A, Najm I, Avanzini G, et al. Terminology and classification of the cortical dysplasias. Neurology 2004;62:S2-S8 , .
    • . . . Malformations of cortical development or cortical dysplasia were identified and classified according to a simplified version of what was described by Palmini et al.22 Due to overlap between the pathology of certain tumors and malformations of cortical development, the limited amount of tissue available for assessment in some cases, and the known lack of reproducibility in the classification (particularly in the Malformation of Cortical Development and Focal Cortical Dysplasia type-I categories; see Table 1), the Palmini et al classification was simplified to include only type-I and type-II forms . . .
    • . . . Table 1 summarizes the terminology and classification of malformations of cortical development and focal cortical dysplasia per Palmini et al and the classification used in this study.22 Mesial temporal sclerosis or hippocampal sclerosis was defined by a characteristic loss of neurons and gliosis in the hippocampal region, preferentially involving the dentate, CA4, CA3, and CA1 regions.23 Hamartias were defined as collections of small neurons marked by scant cytoplasm and pericellular clearing.24 Heterotopias were marked by the presence of disordered gray matter tissue in the white matter.25 . . .
  23. Blümcke I, Thom M, Wiestler OD. Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 2002;12:199-211 , .
    • . . . Table 1 summarizes the terminology and classification of malformations of cortical development and focal cortical dysplasia per Palmini et al and the classification used in this study.22 Mesial temporal sclerosis or hippocampal sclerosis was defined by a characteristic loss of neurons and gliosis in the hippocampal region, preferentially involving the dentate, CA4, CA3, and CA1 regions.23 Hamartias were defined as collections of small neurons marked by scant cytoplasm and pericellular clearing.24 Heterotopias were marked by the presence of disordered gray matter tissue in the white matter.25 . . .
    • . . . A variety of explanations have been provided.23, 40 Whether the morphologic findings of hippocampal sclerosis are secondary to chronic epilepsy related to the coexistent tumor or whether the coexistence of hippocampal sclerosis represents serendipity, is uncertain. . . .
  24. Armstrong DO. Epilepsy-induced microarchitectural changes in the brain. Pediatric Dev Pathol 2005;8:607-614 , .
    • . . . Table 1 summarizes the terminology and classification of malformations of cortical development and focal cortical dysplasia per Palmini et al and the classification used in this study.22 Mesial temporal sclerosis or hippocampal sclerosis was defined by a characteristic loss of neurons and gliosis in the hippocampal region, preferentially involving the dentate, CA4, CA3, and CA1 regions.23 Hamartias were defined as collections of small neurons marked by scant cytoplasm and pericellular clearing.24 Heterotopias were marked by the presence of disordered gray matter tissue in the white matter.25 . . .
    • . . . Small hamartias are commonly observed in the hippocampus and amygdala in patients with chronic epilepsy and likely represent small foci of disorganized or incomplete development.24 Their significance and contribution to epilepsy is uncertain . . .
  25. Hannan A, Servotte S, Katsnelson A, et al. Characterization of nodular neuronal heterotopia in children. Brain 1999;112:219-238 , .
  26. Lach B, Duggal N, DaSilva VF, et al. Association of pleomorphic xanthoastrocytoma with cortical dysplasia and neuronal tumors: a report of three cases. Cancer 1996;78:2551-2563 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  27. Wang M, Tihan T, Rojiani AM, et al. Monomorphous angiocentric glioma: a distinctive epileptogenic neoplasm with features of infiltrating astrocytoma and ependymoma. J Neuropath Exp Neurol 2005;64:875-881 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  28. Lellouch-Tubiana A, Boddaert N, Bourgeois M, et al. Angiocentric neuroepithelial tumor (ANET): a new epilepsy-related clinicopathological entity with distinctive MRI. Brain Pathol 2005;15:281-286 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  29. Halper J, Scheithauer BW, Okasaki H, et al. Meningo-angiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles. J Neuropathol Exp Neurol 1986;45:426-446 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  30. Prayson RA. Meningioangiomatosis: a clinicopathologic study including MIB-1 immunoreactivity. Arch Pathol Lab Med 1995;119:1061-1064 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  31. Perry A, Kurtkaya-Yapicier O, Scheithauer BW, et al. Insights into meningioangiomatosis with and without meningioma: a clinicopathologic and genetic series of 24 cases with review of the literature. Brain Pathol 2005;15:55-65 , .
    • . . . Rare instances of cortical dysplasia have been described in association with other glioma types.16 Although no pleomorphic xanthoastrocytomas were diagnosed in this series, cases of this tumor and coexistent cortical dysplasia have been reported by others.26 Two lesions encountered in the current series, which have typically not been reported to be associated with malformation of cortical development, include the newly codified angiocentric glioma and meningioangiomatosis;27, 28, 29, 30, 31 the significance of this finding in these rare lesions is not known and may warrant a more systematic examination of these lesions to look for for coexistent malformation of cortical development . . .
  32. Prayson RA. Composite ganglioglioma and dysembryoplastic neuroepithelial tumor. Arch Pathol Lab Med 1999;123:247-250 , .
    • . . . Rare similar cases have been reported in the literature.32, 33, 34 The finding of an associated malformation of cortical development adjacent to this lesion is not surprising, given the association with both of these tumor entities . . .
  33. Hirose T, Scheithauer BW. Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma. Acta Neuropathol 1998;95:649-654 , .
    • . . . Rare similar cases have been reported in the literature.32, 33, 34 The finding of an associated malformation of cortical development adjacent to this lesion is not surprising, given the association with both of these tumor entities . . .
  34. Shimbo Y, Takahashi H, Hayano M, et al. Temporal lobe lesion demonstrating features of dysembryoplastic neuroepithelial tumor and ganglioglioma: a transitional form? Clin Neuropathol 1997;16:65-68 , .
    • . . . Rare similar cases have been reported in the literature.32, 33, 34 The finding of an associated malformation of cortical development adjacent to this lesion is not surprising, given the association with both of these tumor entities . . .
  35. Furuta A, Takahashi H, Ikuta F, et al. Temporal lobe tumor demonstrating ganglioglioma and pleomorphic xanthoastrocytoma components. J Neurosurg 1992;77:143-147 , .
    • . . . Similarly, composite tumors, marked by a mixture of pleomorphic xanthoastrocytoma and ganglioglioma, have also been reported.35, 36, 37, 38 Although pleomorphic xanthoastrocytoma has conventionally been considered a form of astrocytoma, immunohistochemical studies have suggested that a subpopulation of cells in the tumor do show evidence of neural differentiation by immunostaining, raising the question as to whether these tumors may be more glioneuronal in nature than purely astrocytic.39 . . .
  36. Perry A, Giannini C, Scheithauer BW, et al. Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature. Am J Surg Pathol 1997;21:763-771 , .
    • . . . Similarly, composite tumors, marked by a mixture of pleomorphic xanthoastrocytoma and ganglioglioma, have also been reported.35, 36, 37, 38 Although pleomorphic xanthoastrocytoma has conventionally been considered a form of astrocytoma, immunohistochemical studies have suggested that a subpopulation of cells in the tumor do show evidence of neural differentiation by immunostaining, raising the question as to whether these tumors may be more glioneuronal in nature than purely astrocytic.39 . . .
  37. Evans AJ, Fayaz I, Cusimano MD, et al. Combined pleomorphic xanthoastrocytoma-ganglioglioma of the cerebellum. Arch Pathol Lab Med 2000;124:1707-1709 , .
    • . . . Similarly, composite tumors, marked by a mixture of pleomorphic xanthoastrocytoma and ganglioglioma, have also been reported.35, 36, 37, 38 Although pleomorphic xanthoastrocytoma has conventionally been considered a form of astrocytoma, immunohistochemical studies have suggested that a subpopulation of cells in the tumor do show evidence of neural differentiation by immunostaining, raising the question as to whether these tumors may be more glioneuronal in nature than purely astrocytic.39 . . .
  38. Vajtai I, Varga Z, Aguzzi A. Pleomorphic xanthoastrocytoma with gangliogliomatous component. Pathol Res Pract 1997;193:617-621 , .
    • . . . Similarly, composite tumors, marked by a mixture of pleomorphic xanthoastrocytoma and ganglioglioma, have also been reported.35, 36, 37, 38 Although pleomorphic xanthoastrocytoma has conventionally been considered a form of astrocytoma, immunohistochemical studies have suggested that a subpopulation of cells in the tumor do show evidence of neural differentiation by immunostaining, raising the question as to whether these tumors may be more glioneuronal in nature than purely astrocytic.39 . . .
  39. Powell SZ, Yachnis AT, Rorke LB, et al. Divergent differentiation in pleomorphic xanthoastrocytoma: evidence of for a neuronal element and possible relationship to ganglion cell tumors. Am J Surg Pathol 1996;20:80-85 , .
  40. Wieser H-G. Mesial temporal lobe epilepsy with hippocampal sclerosis-ILAE Commission Report. Epilepsia 2004;45:695-714 , .
    • . . . A variety of explanations have been provided.23, 40 Whether the morphologic findings of hippocampal sclerosis are secondary to chronic epilepsy related to the coexistent tumor or whether the coexistence of hippocampal sclerosis represents serendipity, is uncertain. . . .
  41. Fischer-Williams M, Dike GL. Brain tumors and other space-occupying lesions. In: Niedermeyer E, DaSilva FL (eds). Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. 3rd edn. Williams and Wilkins: Baltimore, MD, 1993, pp 305-432 , .
    • . . . In many cases, the tumor itself is electrically silent and the origin of seizures is from the tissue adjacent to the tumor.41 Abnormalities in the adjacent tissue, accounted for by a second epileptogenic pathology, would provide an explanation for seizures in this setting . . .
  42. Chamberlain WA, Cohen ML, Gyure KA, et al. Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development). Epilepsia 2009;50:2593-2598 , .
    • . . . Despite limitations to the reproducibility of diagnoses in the arena of malformation of cortical development/cortical dysplasia,42 particularly when dealing with the Palmini et al Malformation of Cortical Development/Focal Cortical Dysplasia type-I lesions, attempts should be made to identify these findings when evident. . . .
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