Long-term epilepsy associated-tumors (LEATs): what is new? / Tumores associados a epilepsia de longa duração: o que há de novo?

Abstract Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.

Resumo Tumores associados a epilepsia de longa duração constituem uma série de neoplasias asatrocitárias ou glioneuronais que comumente incidem em crianças, adolescentes e jovens adultos e que são histologicamente benignos (OMS grau 1), de localização neocortical e predominantemente situados nos lobos temporais. Clinicamente, a epilepsia crônica refratária é, de modo geral, o único sintoma. Gangliogliomas (GG) e tumores neuroepiteliais disembrioplásticos (DNT) são as entidades mais representativas associadas a astrocitomas pilocíticos (AP) e gliomas angiocêntricos (GA). Estudos moleculares recentes permitiram a definição de novas entidades clínico-patológicas reconhecidas pela classificação de tumores cerebrais da OMS 2021. Algumas delas, como o astrocitoma difuso MIB ou MIBL1 alterados, o tumor neuroepitelial polimorfo do jovem (PLNTY) e o tumor neuronal multilocular e vacuolizado (MVNT) são atualmente considerados tumores associados a epilepsia de longa duração. A relação entre este grupo de tumores e epilepsia é ainda debatida e há um consenso geral sobre o benefício prognóstico de intervenção cirúrgica precoce.

MRI classification and imaging findings of dysembryoplastic neuroepithelial tumors / 中华放射学杂志

Objective To investigate the MRI classifications and imaging findings of dysembryoplastic neuroepithelial tumor(DNET). Methods MR images of 34 patients with pathologic confirmed DNET of Beijing Sanbo Brain Hospital were retrospectively reviewed in this study. The classification was made according to the number of pseudocysts, scope of involvement, morphology and location. Results MRI appearances of DNET were divided into three subtypes: cystic‐like, polycystic‐like and diffuse type. Twelve cases had cystic cortical, including front lobe (5 cases), temporal lobe (5 cases), parietal lobe (2 cases). These cases presented quasi‐circular or oval shape, with hypointense on T1WI and strongly hyperintense on T2WI. T2‐FLAIR was observed hyperintense ring sign in the tumor periphery and the cystic content was close to CSF but having the largest difference to that of CSF, which signal was higher than CSF. Twenty cases were polycystic‐like, front lobe (7 cases), temporal lobe (7 cases), parietal lobe (5 cases), occipital lobe (1 case). In these 20 cases, they had slightly hypointense on T1WI and strongly hyperintense on T2WI. Located in the cortex and subcortical matter, with wedge shape, gyriform or triangle shape.On T2‐FLAIR, internal septation and hyperintense"ring sign"were observed. Two cases were diffuse type, bilateral (1 case), unilateral (1 case). In these 2 cases, diffuse lesions involving multiple areas with hyperintense ring and internal septation on FLAIR, including subcortical white matter, deep nucleus and periventricular area. Conclusions The MR appearances of DNET are variable. Understanding the MR imaging type of DNET might improve the MR diagnosis of DNET.

Clinicopathologic features of infant dysembryoplastic neuroepithelial tumor: a case report and literature review / 北京大学学报(医学版)

Dysembryoplastic neuroepithelial tumor (DNT) has traditionally been viewed as rare benign tumors that present with seizure widely considered curable with surgery alone.Most DNTs occur in childhood and young adults.However,rare reported cases occur in infants.This paper reported an infant case of DNT and its diagnosis,differential diagnosis,treatment,molecular features and prognosis based on the review of current literatures.The age onset of this patient was only 11 months old.The clinical manifestations were partial seizures and the imaging data untypical;CT and MRI were all supportive of astrocytoma.Typical glioneuronal element histologic features could be seen,which contained oligodendrocyte-like cells attached to bundles of axons and neurons floating in a myxoid interstitial fluid.Meanwhile,some atypical regions could also be seen.These atypical regions showed a mixture of oligodendrocyte-like cells and neurons without a myxoid interstitial fluid,which were easily misdiagnosed.The BRAFV600E mutation was not detected.This patient had a good response to drug therapy.Totally surgical resection of the tumor was conducted.The patient had been seizures free for 6 months.In conclusion,DNT is a rare and well prognostic tumor (WHO grade Ⅰ),which most often arise in children in the setting of medically refractory epilepsy.The most common tumor location was temporal.Because clinical symptoms,imaging and histological features of DNT and other low-grade gliomas broadly overlap such as ganglioglioma,pilocytic astrocytomas and oligodendroglioma et al.,differential diagnosis should be made carefully.The glioneuronal element was the histopathological hallmark of DNT.In addition,some untypical regions should also be called attention.Although BRAFV600E mutation didn't exist in this case,it played a role in differential diagnosis because it has been previously recorded that BRAFV600E mutation was a common feature of DNT.Infant patients have their own characteristics.For example,drug therapy worked well and the imaging data was untypical.Doctors should improve the understanding of this disease to avoid unnecessary radiotherapy or chemotherapy.

Evaluation of 3.0T 1H-MR spectroscopy imaging in the diagnosis and grading of gliomas / 肿瘤研究与临床

Objective To investigate the value in MR spectrum of diagnosis and grading of gliomas.Methods 36 cases of patient with gliomas who confirmed by histopathologic findings or clinical follow-up were collected. Using a GE Signa EXCITE HD 3.0T super conduct MR unit, all the cases of patients were performed conventional MR scan and multi-voxel with 2-D multi-voxel PRESS 144 ms. Functool software was used for post-processing of spectrum. The ratios of NAA/Cr, NAA/Cho, Cho/Cr were measured in the solid part of masses, circum of tumors and contralateral parenchyma respectively. The result was processed by the statistical method. Results The statistical analysis was exacted by SAS 8.2 software. In the solid part of masses, there were significant differences between low-grade gliomas and high-grade gliomas in the ratios of Cho/Cr, Cho/NAA、NAA/Cr and MI (P ＜0.05), but in peritumoral edema, there were significant differences in the ratios of Cho/Cr, NAA/Cr (P ＜0.05), and no significant differences in the ratios of MI (P ＜0.05).Conclusion 1H-MRS is very important and useful in the evaluation of gliomas. It has made it possible to exactly evaluate the grade of gliomas combined with other imagings.

Clinical and neuroimaging features of gliomatosis cerebri confirmed by neuropathology / 中华神经科杂志

Objective To study the clinical and neuroimaging features of gliomatosis cerebri(GC)so as to enhance the accuracy of diagnosis. Methods The clinical manifestations and cranial MRI characteristics of 10 cases of GC confirmed by neuropathology of brain biopsy were analyzed. Results Main clinical features of the 10 patients were not so severe and varied with headache, dizziness, dementia,aphasia, epilepsy, etc. Cranial MRI scan showed diffuse long T2 signals in frontal lobes, temporal lobes,parietal lobes, occipital lobes bilaterally, as well as corpus collosum, thalamus, paraventricular white matter, caudate nucleus and putamen. Brain stem and cerebellum were also involved. The borders of the lesions were unclear and no obvious mass effect was found. Contrast enhancement was positive only in 3 patients after Gd-DTPA injection. The lesions were always bilateral without cystic formation or hemorrhage.DWI signals of 8 cases were in accordance with pathological grades. Cho/Cr and Cho/NAA ratio increased in all 7 cases with MRS imaging. Cho/Cr in tumor area versus normal area was 1.28 ±0. 15 vs 0. 92 ±0. 17(t=4.201,P=0.0012,95% CI:0.17-0.57).The value of Cho/NAA was 3.21 ± 1.19 vs 0.61 ±0.18(t = 5.716,P=0.0001,95 % CI:1.61-3.59).Biopsy pathological examination showed diffuse infiltrative growth of astroglioma cells of 8 cases with low-grade while 2 cases with high-grade. Conclusions Mismatch between relatively slight clinical manifestations and heavy diffuse imaging features are important in the diagnosis of GC, with the aid of brain biopsy. MRS would contribute to diagnosis and DWI signal may be correlated with GC grade and help judging prognosis.

Diagnostic value of apparent diffusion coefficient value in prediction of grade for neuroepithelial tumors / 中华放射学杂志

Objective To investigate the predictive value of ADC value in grading of neuroepithelial tumors. Methods The clinical data and images of 70 patients with neuroepithelial tumors pathologically proven were collected and analyzed restrospectively. All the patients were classified into low(WHOⅠ or Ⅱ)and high(WHO Ⅲ or Ⅳ)grade groups which included 40 and 30 cases respectively accroding to the 2007 WHO classification of tumours of the central nervous system. All the patients underwent plain and contrast-enhanced MR scan and DWI before surgery. The minimum ADC(MinADC)value was measured postoperatively on ADC maps. The Ki-67 labeling index(Ki-67 LI)of tumor tissue was determined by immunohistochemistry.MinADC values for two groups were analyzed using student t test, while the age and Ki-67 LI for the two groups was analyzed using Mann-Whitney test(P＜0.05 considered to be significant＝.Also the MinADC valHe and Ki-67 LI were analyzed with Pearson correlation. The receiver operating characteristic analysis was used for evaluation for grading neuroepithelial tumors of the patients using MinADC. Results The mean MinADC value[(1.08±0.31)×10~(-3) mm~2/s]of the low grade group was significantly higher than that[(0.74±0.18)×10~(-3) mm~2/s]of the high grade group(t=5.42,P＜0.05＝,and the Ki-67 LI of the low grade group[0-50%,median 4%]was significantly lower than that[0-75%,median 25%]of the high grade group(U=325.50,P＜0.05＝.There was a negative correlation between MinADC value and Ki-67 LI(r=-0.30,P＜0.05＝.The area under the ROC curve was 0.85,and the cutoff MinADC value of 0.86×10~(-3) mm~2/s for the differentiation between high and low grade neuroepithelial tumors provided the best combination of sensitivity(90.0%)and specificity(77.5%)(receiver operatingcharacteristic analysis).Conclusion MinADC value is helpful for prediction of neuroepithelial tumor grade.

Nerve growth factor and its receptors in tumors of nervous system / 国际肿瘤学杂志

Nerve growth factor (NGF) and its high affinity receptor tyrosine kinase (TrkA)are indis-pensable for the development of nervous system. Latest researches reveal that over-expression of NGF and TrkA is related to better outcome in neuroblastoma and medulloblastoma. While in glioma, the over-expression and nuclear translocation of NGF and TrkA are indicators of malignant degree. Study of the expression and sub-cel-lular cocalization of NGF and TrkA can provide new way for the diagnosis and therapy of nervous system tumors.

Astroblastoma: A Case Report

Astroblastoma is one of the very unusual type of tumors, whose histogenesis has not been clarified. It occurs mainly among children or young adults. Astroblastoma is grossly well-demarcated, and shows histologically characteristic perivascular pseudorosettes with frequent vascular hyalinization. Perivascular pseudorosettes in astroblastoma have short and thick cytoplasmic processes and blunt-ended foot plates. A 15-yr-old girl presented with headache and diplopia for one and a half year. A welldemarcated mass, 9.7 cm in diameter, was found in the right frontal lobe in brain MRI, and it was a well-enhanced inhomogenous mass. Cystic changes of various sizes were observed inside the tumor mass as well as in the posterior part of the mass, but no peritumoral edema was found. Histologically, this mass belongs to a typical astroblastoma, and no sign of anaplastic astrocytoma, gemistocytic astrocytoma or glioblastoma was found in any part of the tumor. Immunohistochemically, the tumor cells showed diffuse strong positivity for glial fibrillary acidic protein, S-100 protein, vimentin and neuron specific enolase, and focal positivity for epithelial membrane antigen and CAM 5.2, while showing negativity for synaptophysin, neurofilament protein, pan-cytokeratin and high molecular weight keratin.

Ganglion Cell Tumors

BACKGROUND: In ganglion cell tumos, immunohistochemical characteristics and malignant changes of neuronal cells and the usefulness of the MIB-1 (Ki67) indices for granding ganglion cell tumors and abnormalities of the adjacent nonneoplastic cortex have been issued. METHODS: The clinicopathologic features of 34 surgically resected ganglion cell tumors (32 gangliogliomas and 2 gangliocytomas) were retrospectively analysed, and immunohistochemical characteristics and malignant changes of neuronal cells and the usefulness of the MIB-1 (Ki67) indices for grading ganglion cell tumors and abnormalities of the adjacent normal cortex were investigated using various immunohistochemical studies. RESULTS: According to the Daumas-Duport grading system, there were 24 (70.6%) grade II, 8 (23.5%) grade III, and two (5.9%) grade IV cases. Malignant transformation was present only in the glial (7 cases) or both glial and neuronal (3 cases) components. The MIB-1 indices were statistically significant (p<0.001): grade II was 0.0-1.05% (0.27+/-0.3%), grade III was 0.8-8.02% (2.8+/-3.2%), and grade IV was 3.0-4.99% (3.99+/-1.0). Anaplasia and MIB-1 positivity was observed among the neurons in the three cases. Perikaryal cytoplasmic expression or surface punctate accentuation of synaptophysin were noted only in the neoplastic neurons in some cases. Fifteen out of 20 cases, which included the nonneoplastic cerebral cortex, displayed mild cortical dysplasia (microdysgenesis). CONCLUSIONS: The neuronal component also showed malignant transformations with proliferating activity. In our study, synaptophysin-immunoreactive patterns of neoplastic neurons were unique. The MIB-1 indices were helpful for grading ganglion cell tumos. Only mild cortical dysplasia was present in the normal cortex adjacent to the tumor.

Neuroradiologic and clinicopathologic features of dysembryoplastic neuroepithelial tumor / 中华放射学杂志

Objective To evaluate MRI or CT appearance and clinicopathologic features of dysembryoplastic neuroepithelial tumor (DNT). Methods MRI or CT appearance and clinicopathologic features in 12 cases of histopathology confirmed DNT were retrospectively studied. Results There were 6 men and 6 women, and the age ranged from 12 to 68 years with the average age of 36.7 years. Most patients had partial seizures, but the neurological deficits were absent. All lesions were located in the supratentorial region and involved the cerebral cortex on MRI scan. Localization of lesions was predominantly in the frontal (n=4) and temporal (n=3) lobes. The maximum lesion diameter ranged in size from 2 cm to 5 cm, and the lesion showed round, lobular- or irregular-shaped. The white matter was involved in 2 cases, and 7 were with cystic change (58.3%). All lesions were hypointense on T1-weighted images and hyperintense on T2-weighted images as well as devoid of peritumoral edema or mass effect. MRI signal intensity of cystic lesions was homogeneous on T1-weighted images which was equal to or slightly higher than that of cerebrospinal fluid. CT scan of 6 cases disclosed moderately hypodense lesion, 2 of which were markedly hypodense cystic-lobular shaped, and foci of calcification was observed in 1 case. Contrast enhancement was absent in 4 cases and only 1 case showed slight enhancement unevenly. Histologically, the DNT were classified into three subtypes: simple form (n=4), complex form (n=6), and non-specific variant (n=2). All patients experienced lesion gross total or subtotal surgical removal, and had received no chemo- or radiotherapy postoperatively. Conclusion DNT is a benign lesion, and its characterization is better disclosed by MRI compared to CT scan.

Imaging diagnosis of dysembryoplastic neuroepithelial tumors / 中华放射学杂志

Objective To study the imaging characteristics of intracranial dysembryoplastic neuroepithelial tumors(DNT),and to evaluate the role of CT and MRI in their diagnosis.Methods We presented 8 DNTs cases confirmed histopathologically after operation.CT and MRI features were retrospectively analyzed(3 cases received MR scan only and 5 had both studies),compared with the surgical findings and pathological appearance.Results Eight patients had totally 11 tumors with multifoci in 2 cases.Six DNTs were located in the temporal lobe,1 lesion involved the parietal lobe,1 in the frontal lobe,1 in the brain stem,1 in the cerebellum,and 1 in the frontal and temporal lobe simultaneously.All lesions were observed intracortically,and partial of them extended into the subcortical location.On 5 non-contrast CT scans,3 DNTs were homogeneously hypodense;1 case contained isodense nodules within the hypodense focus.Peripheral spotty calcification was found in 1 case.On pre-contrast MR images,all lesions showed hypointense on T_1-weighted images,moreover,multicystic change with more markedly decreased signal intensity was observed.The DNT had a well-demarcated,multinodular gyriform configuration,or a soap bubble appearance at the cortical margin.On T_2-weighted images,high signal intensity of the tumors was seen except for hypointense calcification.The bone remodeling of the adjacent calvaria was noticed in(1 case.) The tumors had slightly increased signal intensity on FLAIR(fluid attenuated inversion recovery) in 2 cases,and homogeneously mild hyperintense on PDW(proton density weighted imaging),while the isointense focus was observed in one case on DWI(diffusion weighted imaging).No obvious enhancement was identified except 1 lesion with mild enhancement following intravenous administration of contrast material.3 tumors had ill-defined contours,whereas the others showed well-demarcated margins.No surrounding vasogenic edema was present except 2 foci with slight edema.Conclusion DNT usually shows characteristic radiologic findings,in combination with the clinical presentation and history,the diagnostic accuracy should be improved,and,as such,unnecessary radiation and/or chemotherapy may be avoided.