Angiocentric Neuroepithelial Tumor (ANET): A New Epilepsy-Related Clinicopathological Entity with Distinctive MRI (original) (raw)
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A b s t r a c t Angiocentric glioma (AG) is a newly-classified, very rare, WHO grade I central nervous system (CNS) lesion, occurring usually in children and young adults. Only 52 patients with AG have been reported so far, making it one of the rarest neuropathological entities. Hereby we present two new cases of AG in young subjects with detailed neuropatholog-ical investigations and a neuroradiological picture along with a brief summary of all already published literature reports of this tumor. Histopathological examination of the resected tissue from both cases revealed similar changes characteristic of AG. The tumors were composed of spindle-like, elongated cells, forming characteristic pseudorosettes around vessels and diffusively infiltrating surrounding tissue, trapping neurons between tumor cells. Noticeably, some neoplastic cells encrusting vessels extended far beyond the main tumor mass. Hypothetically, this may be responsible for the recurrence of the tumor even in the case of apparently total excision. In immunohistochemistry, AG cells were glial fibril-lary acidic protein (GFAP) and vimentin positive, also exhibiting a strikingly significant epithelial membrane antigen (EMA) dot-like staining pattern. In one of the cases, electron microscopy revealed ependymal differentiation features such as microvilli and cilia. Taken together, all these data strongly confirm a dual astroglial-ependymal nature of the tumor. Follow up corroborates benign character of this neoplasm. Both AGs reported here were immunonegative for the product of the mutated IDH-1 gene what, according to our best knowledge, has never been reported so far. It may suggest that in their pathogenesis AGs differ from grade II astrocytomas, which in most cases harbor a mutation of IDH-1. Noteworthy, neuroimaging in our cases was relatively characteristic but not conclusive, therefore biopsy (at least) is mandatory. A newly proposed so called " A-B-C " classification of long-term epilepsy-associated tumors (LEATs) places AG in a category named ANET. The authors shortly review the A-B-C classification of LEATs.
Angiocentric glioma: a rare intractable epilepsy-related tumour in children
Folia Neuropathologica, 2014
Angiocentric glioma is a low-grade tumour that occurs in children and young adults with a long-standing epilepsy. The typical histopathological features of this tumour is the presence of spindle-shaped cells, radially oriented around the cortical blood vessels. We present two teenage cases of the angiocentric variant of glioma: 1) a 15-year-old girl with a chronic and intractable partial epilepsy with cystic tumour located in the right temporal lobe and 2) a 14-year-old boy with intractable seizures and an extensive cortical lesion in the left parieto-occipital area. In both cases, the total tumours excision was performed. The histopathological findings revealed a characteristic angiocentric pattern that was composed of elongated cells arranging in pseudorosette-like structures around blood vessels. Moreover, schwannoma-like areas and subpial neoplastic infiltration with palisading of tumour cells at the brain surface were seen. The neoplastic cells displayed immunoreactivity for GFAP, S-100 protein and vimentin. A slight "dot-like" EMA staining, suggesting ependymal differentiation, was detected. The clinical and pathological picture allowed to establish the diagnosis of angiocentric gliomas. The patients were discharged home in a good condition and without seizures. During the 4-year follow-up, the tumour recurrence and seizures were not observed. The appropriate diagnosis of this peculiar type of usually low-grade glial tumour is important for adequate and successful treatment. The differential diagnosis requires the exclusion of other tumours with an angiocentric pattern, i.e. ependymoma, astroblastoma, which are associated with more aggressive biology.
Histology and histopathology, 2001
The group of brain tumors with mature components encompasses several pathological entities including: the ganglioneuroma; the gangliocytoma; the ganglioglioma; the desmoplastic ganglioglioma; the neurocitoma and a group of glioneuronal hamartomatous tumorous lesions, such as meningoangiomatosis. The dysembryoplastic neuroepithelial tumor is characterized by the presence of multiple cortical nodules made up of small, oligo-like cells and a myxoid pattern rich in mucopolysaccharides. Mature neuronal cells are frequently detected throughout the tumor. Most of them are associated with microhamartias in the adjacent brain and pharmacoresistant epilepsy. The excellent prognosis of the majority of these tumors and the potential for malignant transformation of the glial component in the ganglioglioma are the two most remarkable findings. Histological signs of anaplasia and greater mitotic and proliferative activities are associated with local recurrences. Atypical neurocytomas occur only ex...
Journal of Neuropathology and Experimental Neurology, 2005
We present 8 examples of a neoplasm with features of both astrocytoma and ependymoma that may represent a distinct clinicopathologic entity. The cerebral hemispheric tumors occurred in patients that were 3, 4, 12, 14, 15, 26, 30, and 37 years of age. All presented with seizures that, with the exception of 2, began in childhood. Magnetic resonance imaging studies showed ill-defined, T2-hyperintense, generally noncontrast-enhancing lesions that, although centered on the cortex or amygdala, extended into the underlying white matter for a short distance. Histologically, the variably infiltrative tumors were distinctively angiocentric with welldeveloped perivascular pseudorosettes in some cases. Longitudinal and/or circumferential orientations of perivascular cells were common also. The cells were uniform in their cytologic features from case to case and were bipolar in all but one case. A glial nature was inferred from immunoreactivity for GFAP, and ependymal differentiation was suggested by positivity for EMA in three cases and ultrastructural features in one. Overall, the tumors were biologically indolent except for one that recurred and ultimately proved fatal.
Dysembryoplastic neuroepithelial tumors and gangliogliomas: clinical results of 52 patients
Acta Neurochirurgica, 2010
Purpose Dysembryoplastic neuroepithelial tumors (DNET) and gangliogliomas (GG) are generally associated with epilepsy in young patients. Presurgical work-up and postsurgical results vary from center to center. Seizures are commonly focal with secondary generalization, and surgical treatment is often effective. Methods Twenty-eight patients with DNET and 24 patients with GG were eligible for this retrospective study. The authors present clinical, radiological, and pathological characteristics and seizure outcome of 52 patients histopathologically diagnosed with either a DNET or a GG. Results Characteristically the majority of the tumors showed hypointensity on T 1 -weighted images and increased signal intensity on both T 2 -weighted and FLAIR images. At the last follow-up (mean 54.3 months), overall favorable seizure outcome was 94.2% (n=49). Twenty-six (92.8%) patients with DNET and 21 (87.5%) patients with GG were seizure free. Complete drug withdrawal was achieved in 26 (50%) patients. Shorter duration of epilepsy (p=0.02), absence of status epilepticus (p=0.01), absence of edema on MRI (p=0.03), absence of seizure within the first month of surgery (p=0.002), and total resection (p=0.00001) were associated with favorable outcome with respect to seizure.
Neuropathology
Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5-year-old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET-like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also highgrade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild-type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high-grade regions. By immunohistochemistry there was loss of nuclear alpha-thalassemia mental retardation syndrome, X-linked (ATRX) expression only in the high-grade region. Next-generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high-grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q-codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole-arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy.
Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours
Acta Neuropathologica, 2017
by interrogating our expression data, we were able to show that each molecular group possessed expression phenotypes suggesting different cellular differentiation: astrocytic in one group and oligodendroglial in the second. Informed by this, we were able to identify CCND1, CSPG4, and PDGFRA as immunohistochemical targets which could distinguish between molecular groups. Our data suggest that the current histological classification of glioneuronal tumours does not adequately represent their underlying biology. Instead, we show that there are two molecular groups within glioneuronal tumours. The first of these displays astrocytic differentiation and is driven by BRAF mutations, while the second displays oligodendroglial differentiation and is driven by FGFR1 mutations.
Dysembryoplastic neuroepithelial tumors: MR and CT evaluation
American journal …, 1996
To evaluate dysembryoplastic neuroepithelial tumors (DNTs) on MR and CT studies and to compare DNT with other frequently encountered epileptogenic glioneuronal lesions. METH-ODS: We analyzed the MR images and CT scans of 16 patients who had complex partial epilepsy and DNT with respect to tumor location, size, CT density, MR signal intensity, mass effect, contrast enhancement, and heterogeneity, and compared these features with CT and MR findings in 51 cases of ganglioglioma and 33 cases of glioneuronal malformation. RESULTS: DNTs were located in the temporal lobe in 14 patients and in the frontal lobe in 2 patients. The cortex was involved in all cases and the subcortical white matter in 10 cases. Fifty percent of the tumors had poorly defined contours. On MR images, 14 DNTs had multiple cysts and 2 had single cysts. Contrast enhancement was observed in 6 DNTs, and mass effect was present in 9. CT scans disclosed moderately hypodense lesions in 7 patients and markedly hypodense cystic lesions in 6 patients. Two DNTs were calcified. Tumor hemorrhage with perifocal edema was observed in 1 case. Contrary to previous reports, slow but definite tumor growth was present during a 13-year period in 2 of 6 patients in whom serial CT or MR studies were obtained. CONCLUSION: A multicystic appearance on MR images is a characteristic feature of DNT and corresponds to its myxoid matrix and multinodular architecture. This feature is rare in gangliogliomas and glioneuronal malformations, and, as such, may help differentiate DNTs from these disorders.
Histopathology-Reviews and Recent Advances 196 2.2. Central neurocytoma and extraventricular neurocytoma Central neurocytoma and extraventricular neurocytoma are WHO grade II tumors composed of regular rounded cells that have undergone neuronal differentiation. Central neurocytomas are typicaly located within the lateral ventricles just next to the foramen of Monro, whereas extraventricular neurocytomas are located within the brain parenchyma. Both characteristically occur in young adults. The outcome is favorable after complete resectioning. 2.3. Dysembryoplastic neuroepithelial tumor Dysembryoplastic neuroepithelial tumor (DNT) is frequently a benign, supratentorial glialneuronal WHO grade I tumor. DNT occur mainly in children or young adults, who usually present with intractable partial complex seizure. Characterized by a predominantly cortical location, DNT histopathologically exhibits a complex columnar and multinodular architecture, and is often associated with cortical dysplasia. 2.4. Desmoplastic infantile astrocytoma and desmoplastic infantile ganglioglioma Desmoplastic infantile astrocytomas (DIAs) and desmoplastic infantile gangliogliomas (DIGs) are almost WHO grade I tumors that are often cystic and commonly occur in infants. Composed of a prominent desmoplastic stroma with neuroepithelial components, mainly neoplastic astrocytes in DIAs or astrocytes together with variable neuronal components in DIGs, they involve the cerebral cortex and leptomeninges, and are often adherent to the dura. The natural course is benign. 2.5. Rosette-forming glioneuronal tumor of the fourth ventricle Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) is a usually rare and slowly growing WHO grade I tumor. It is commonly affecting young adults, RGNT is composed of two distinct histological cells types; uniform neurocytes which form rosettes and/or perivascular pseudorosettes and astrocytic cells similar to pilocytic astrocytomas. The prognosis is good upon surgical removal. 2.6. Cerebellar liponeurocytoma This rare type of cerebellar tumors is WHO grade II tumor that typically occurs in adults. It is Composed of neuronal, astrocytic, and some lipomatous cells, they tend to recur after initial treatment. 2.7. Papillary glio-neuronal tumor Papillary glio-neuronal tumors is a well defined and benign with WHO grade I. the natural course is insidius. It is composed of flat to cuboidal, GFAP-positive astrocytes lining Neuronal and Mixed Neuronal-Glial Tumors of the Central Nervous System 197 hyalinized vascular pseudo-papillae and synaptophysin-positive interpapillary sheets of neuronal cells. Upon microscopy, it exhibits different sizes of large and intermediate neuron "ganglioid" cells. 2.8. Spinal paraganglioma Spinal paraganglioma is encapsulated, benign, neuro-endocrine WHO grade I tumor. Arising from neural crest cells and composed of segmental or collateral autonomic ganglia (paraganglia), It is primarily involving the cauda equine and filum terminale region. The uniform main cells exhibit neuronal differentiation and forming compact nests (Zellballen) surrounded by cells and a delicate capillary network within the CNS. 3. Gangliogliomas and gangliocytomas 3.1. Definition Gangliogliomas and gangliocytomas are well-differentiated, slowly growing benign neuroepithelial neoplasms that consist of neoplastic, mature ganglion cells. Both gangliogliomas and gangliocytomas are a type of neuroepithelial tumor that is the most frequent pathology observed in patients with long-term epilepsy. A gangliocytoma in the absence of neoplastic glial-cell development and a ganglioglioma in the presence of neoplastic glial-cell development. (1) 3.2. WHO grading Gangliocytomas and most gangliogliomas are categorized as WHO grade I tumors (1). Some gangliogliomas with anaplastic features of the glial component are categorized as WHO grade III tumors (anaplastic gangliogliomas). Criteria for grade II types has also been suggested (2, 3). 3.3. Incidence and gender distribution These uncommon neoplastic lesions represent only 0.4% of all CNS tumors and 1.3% of all brain tumors (3,4). The age of patients is variable, ranging from 2 months to 70 years. Data from 5 large series of a total of 626 patients indicate an average age at diagnosis ranging from 8.5 to 25 years and a male: female ratio ranging from 1.1:1 to 1.9:1 (5,6,7,8). In one study, the mean age in children at diagnosis is 9.5 years, with a slight female prevalence (9). 3.4. Localization The vast majority of gangliogliomas (>70%) occur in the temporal lobe. However, Gangliocytomas and most gangliogliomas may occur throughout the CNS, including in the Histopathology-Reviews and Recent Advances 198 cerebrum, brain stem, cerebellum, spinal cord, optic nerves, and pituitary and pineal glands.