Neuropathologic study of massive subcortical heterotopia / 中华病理学杂志

Objective@#To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia.@*Methods@#Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017.@*Results@#All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period.@*Conclusions@#Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

Application of ATRX in diagnosis and prognostic evaluation of glioma / 中华病理学杂志

Objective@#To investigate the diagnostic and prognostic implications of ATRX mutation and p53 mutation in patients with glioma.@*Methods@#The clinicopathologic and molecular features of Chinese adult glioma patients, including diffuse and anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss expression and p53 overexpression.@*Results@#Loss of ATRX expression was seen in 85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX expression combined with normal p53 expression survived longer(P=0.013).@*Conclusions@#ATRX mutation is a molecular marker for astrocytic tumors. ATRX mutation combined with p53 mutation can predict prognosis of patients with glioma.

Diagnostic and prognostic roles of loss of CIC protein expression in oligodendroglial tumors / 中华病理学杂志

Objective@#To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication.@*Methods@#The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed.@*Results@#The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249).@*Conclusions@#Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

Expression of autophagy-related proteins in malformations of cortical development / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of autophagy-related proteins (Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis.</p><p><b>METHODS</b>The brain tissue of 18 cases with epileptogenic foci resection, including 6 cases of tuberous sclerosis complex (TSC), 6 cases of focal cortical dysplasia type IIb (FCD IIb) and 6 cases of focal cortical dysplasia type I (FCD I), were retrieved. Immunohistochemical study for Beclin-1, LC3 and p62 proteins was performed. The degree of positivity for Beclin-1 and LC3 proteins was compared. Western blot was used to quantitatively analyze the LC3 protein in focal lesion of each disease groups.</p><p><b>RESULTS</b>Immunohistochemical study showed that the three proteins were mainly expressed in the dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb. The positivity was more intense in the dysmorphic neurons than the other cell types. Immunostaining for Beclin-1 showed granular or diffuse cytoplasmic positivity, in addition to the strong expression in axons. On the other hand, LC3 showed diffuse or perinuclear cytoplasmic expression. The staining for p62 was mainly cytoplasmic or perinuclear and sometimes nuclear. In FCD type I, only individual cells showed positive expression for the three proteins. The number of Beclin-1 and LC3-positive cells was larger in TSC group, followed by FCD IIb group and FCD I group.And there were significant differences between TSC group and FCD I group, as well as FCD IIb group and FCD I group (P<0.05). Quantitative expression of LC3 protein by Western blot showed smaller amount in TSC group, followed by FCD IIb group and FCD I group.</p><p><b>CONCLUSIONS</b>The dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb show abnormality in autophagy, resulting in intracytoplasmic protein accumulation. There are differences in molecular pathogenesis in these cell types.</p>

Clinicopathological study of non-Langerhans cell histiocytosis in central nervous system / 中华内科杂志

Objective To explore the clinicopathological features and imaging characteristics of non-Langerhans cell histiocytosis in central nerve system,thus to facilitate the diagnosis and differential diagnosis.Methods A total of ten cases were enrolled in the study,with seven cases of Rosai-Dorfman disease(RDD) and three cases of xanthoma disseminatum (XD).Data on the clinicopathological features,imaging,immunophenotype and prognosis were collected and analyzed.Results Seven patients with RDD,5 males and 2 females with the mean age of 46.7 years old,all presented as dural-based or intraparenchymal hypo-to isointense lesions on T1 and T2 with post-contrast enhancement.The polymorphous admixture of histiocytes,lymphocytes and plasma cells was observed in a fibrous stroma,with emperipolesis of some histiocytes.The immunohistostaining of CD11c,CD68,MAC387 and S-100 was positive in the histiocytes,while the staining of CD1α was negative.Five patients recovered after the operation,while one patient died of the disease.All the 3 XD patients were female,with the median age of 20.7 years old.All XD patients presented as multiple intraparenchymal hypointense lesions on T1 and hyperintense lesions on T2 with post-contrast enhancement.The infiltration of foam-like histiocytes,a few Touton giant cells,lymphocytes and eosnophils was observed in all XD patients.The immunohistostaining of CD68 and CD11c was positive in the histiocytes and that of MAC387 partly positive,while the staining of S-100 and CD1α was negative.One XD patient survived well,while another one died of the disease.Conclusions The diagnosis of RDD and XD should be based on their typical morphology and immunophenotype and should be differentiated from Langerhans cell histiocytosis and other non-Langerhans cell histiocytosis.Non-Langerhans cell histiocytosis in central nerve system often presents untypical clinical presentation and imaging features,thus the communication and cooperation between clinician and pathologist is needed.