CNS embryonal tumors (CET) other than medulloblastomas (MB) and atypical teratoid/rhabdoid tumors (AT/RTs), previously designated as \'central nervous system primitive neuroectodermal tumors\' (\'CNS PNETs\'), are a heterogenous subset of tumors with poorly defined diagnostic criteria. Other than the subset of embryonal tumor with multilayered rosettes (ETMR) defined by C19MC amplification, most CETs are diagnosed by exclusion of other molecularly defined entities and histological mimics including MB, AT/RTs, and high-grade gliomas, and termed as CET, not otherwise specified (NOS) in the 2016 WHO classification.
To reclassify \'CNS PNETs\' as per WHO 2016, and estimate the true proportion of CET, NOS in a tertiary healthcare setting, and to evaluate the diagnostic utility of C19MC amplification, Lin28A and Olig2 expression in the subclassification of CETs.
Previously diagnosed cases of \'CNS PNETs\' (2002-2016) were first evaluated by immunohistochemistry (IHC) for MIC2, RelaA, L1CAM, IDH1R132H, H3K27M, H3G34R, H3G34V, INI1, and BRG1 proteins and by fluorescence in-situ hybridization (FISH) for EWSR1 translocation to exclude histological mimics. The selected CETs (case cohort) and 79 histological mimics (comparison cohort) comprising of MB, AT/RT, pineal parenchymal tumors, Ewing sarcoma, esthesioneuroblastoma, intraocular medulloepithelioma, and H3G34R mutant high-grade glioma were subject to IHC for Olig2 and Lin28A, and FISH for C19MC amplification.
Twenty-two cases of \'CNS PNETs\' were retrieved, all of which were negative for the first panel of markers and showed retained INI-1/BRG1 expression. Three of them (3/22, 13.6%) showed C19MC amplification (ETMR, C19MC-altered) with ETMR histology, Lin28A positivity, and Olig2 negativity. Among the remaining 19 CETs, one showed medulloepithelioma histology (Medulloepithelioma, NOS) and remaining were non-descript small round cell tumors (CET, NOS), all negative for Lin28A. Olig2 was positive in only 3 CETs (13.6%), all being CET, NOS. All tumors in the comparison cohort were negative for C19MC amplification, Lin28A and Olig2 except for 27% of ATRTs that were Lin28A positive.
ETMR, C19MC-altered constitute less than 14% of CETs, with majority remaining uncharacterized as CET, NOS. Lin28A is 100% sensitive for the detection of C19MC amplification; however, its specificity is limited by its expression in ATRTs. Olig2 expression is seen only in a small subset of CET, NOS and is of limited diagnostic utility.

OBJECTIVE: We aimed to evaluate the usefulness of dynamic contrast-enhanced T1-weighted perfusion magnetic resonance imaging (DCE-pMRI) to predict certain immunohistochemical (IHC) biomarkers of glioblastoma (GB) in this pilot study.
METHODS: We retrospectively reviewed 36 patients (male/female, 25:11; mean age, 53 years; age range, 29-85 years) who had pretreatment DCE-pMRI with IHC analysis of their excised GBs. Regions of interest of the enhancing tumor (ER) and nonenhancing peritumoral region (NER) were used to calculate DCE-pMRI parameters of volume transfer constant, back flux constant, volume of the extravascular extracellular space, initial area under enhancement curve, and maximum slope. IHC biomarkers including Ki-67 labeling index, epidermal growth factor receptor (EGFR), oligodendrocyte transcription factor 2 (OLIG2), isocitrate dehydrogenase 1 (IDH1), and p53 mutation status were determined. The imaging metrics of GB with IHC markers were compared using the Kruskal-Wallis test and Spearman correlation analysis.
RESULTS: Among 30 patients with available IDH1 status, 14 patients (46.6%) had IDH1 mutation. EGFR amplification was present in 24/36 (66.6%) patients. Mean Ki-67 labeling index was 29% (range, 1.5%-80%). p53 mutation was present in 20/36 GBs (55%), whereas OLIG2 expression was positive in 29/36 GBs (80.5%). Various DCE-pMRI parameters gathered from the ER and NER were significantly correlated with IDH1 mutation, EGFR amplification, and OLIG2 expression (P < 0.05). Ki-67 labeling index showed a strong positive correlation with initial area under enhancement curve (r = 0.619; P < 0.001).
CONCLUSIONS: DCE-pMRI could determine surrogate IHC biomarkers in GB via tumoral and peritumoral approach, potential targets for individualized treatment protocols.

Circumventricular organs are specialized brain structures that are located mainly at the midsagittal line, around the third and fourth ventricles, often protruding into the lumen. They are positioned at the interface between the neuroparenchyma and the ventricular system of the brain. These highly vascularized nervous tissue structures differ from the brain parenchyma, as they lack a blood-brain barrier. Circumventricular organs have specialized sensory and secretory functions. It is essential for any pathologist who evaluates brain sections to have a solid knowledge of microscopic neuroanatomy and to recognize these numerous specialized structures within the nervous system as normal and not mistake them for pathological changes. The purpose of this study was to provide, for the first time, a detailed and complete histological description of the healthy canine area postrema and to determine its resemblance to that of other mammalian species. Anatomical dissections with routine histological and immunohistochemical techniques were carried out on ten canine brains. The cellular composition of area postrema proved to be largely comparable to that of other mammal species.

Glioblastomas (GBs) are the most common and lethal primary brain tumors in the adults. Glioblastomas originates either from astrocytes that have accumulated mutations and de-differentiated or from neural stem cells within the subventricular zone (SVZ) in close contact with the vasculature. Recently, several studies have hypothesized that gliomagenesis occurs in perivascular niches with highly invasive peripheral proliferating zones. The purpose of our study was to investigate the pathological and clinical significance of Olig2 and YKL40 immunoexpression in 152 GBs in relationship to the SVZ II and III. Olig2 expressions were successfully detected in 12 (15.58%) of 77 SVZ type II GBs and 16 (21.3%) of 75 SVZ type III GBs, respectively. YKL-40 expression was observed in 45 (58.4%) of 77 SVZ type II GBs and in 17 (22.6%) of 75 SVZ type III GBs, respectively. Stepwise multivariate Cox proportional hazards models were used, and the prognostic factors to significantly impact OS were: PFS < 54 weeks (HR: 5.86; CI: 3.02-11.33; p = 0.00); radiotherapy (HR: 0.34; CI: 0.18-0.60; p = 0.00); radio- and chemotherapy (HR: 0.05; CI: 0.03-0.10; p = 0.0), and YKL-40+ GBs (HR: 1.61; CI: 1.28-2.31; p = 0.01).

SOX10 belongs to the family of transcription factors essential for the development of neural crest, peripheral nervous system and melanocytes. It is presently used in histopathology as a marker of melanocytic differentiation. SOX10 is expressed in normal brain tissue in oligodendrocytes, but the information about SOX10 expression in primary tumors of the central nervous system is quite limited. In this study, we examined the expression of SOX10 and Olig2 by immunohistochemistry in a series of 98 glial tumors and explored their specificity and sensitivity for differential diagnosis of ependymal vs non-ependymal tumors. In addition, we examined the expression of EMA and CD99 in ependymal tumors. SOX10 and Olig2 staining were scored as negative if no positive cells or only a few positive cells (typically up to 1-3%) were found. In all other instances, SOX10 or Olig2 staining was scored as positive. Out of 44 examined ependymal tumors none was found to express SOX10 and 7 specimens showed only a few SOX10-positive cells that likely corresponded to entrapped non-neoplastic oligodendrocytes. In contrast, non-ependymal tumors expressed SOX10 in 26/54 (48%) specimens. Olig2 was positive in 5 out of 44 ependymomas (11%) and 50 out of 54 (93%) non-ependymal tumors (astrocytomas and oligodendrogliomas). EMA and CD99 expression was found in 33/44 (75%) and 11/44 (25%) of ependymomas, respectively. SOX10-positivity rules out the diagnosis of ependymoma among other glial tumors with high confidence.

BACKGROUND: Oligodendrocyte transcription factor 2 (OLIG2) is primarily concentrated in the brain and spinal cord ventricular zone, where this protein stimulates oligodendrocytes and specific neurons, determines motor neuron and oligodendrocyte differentiation, and sustains replication in early development. Recent studies have demonstrated that OLIG2 gene is associated with mental disorders, such as schizophrenia, mood disorder, and obsessive-compulsive disorder (OCD).
METHODS: The aim of the present study was to explore whether OLIG2 gene is associated with OCD in a Chinese Han population through the assessment and analysis of three single nucleotide polymorphisms (SNPs), namely, rs762178, rs1059004, and rs9653711, selected from OLIG2 gene sequences from 400 OCD samples and 459 healthy controls in a case-controlled association study.
RESULTS: We demonstrated three principal results. First, SNP rs762178 was associated with OCD, female OCD, and early-onset OCD; rs1059004 was associated with OCD and early-onset OCD; and rs9653711 was also associated with OCD and early-onset OCD. Second, the pairs of loci rs762178 and rs1059004, rs1059004 and rs9653711, and rs762178 and rs9653711 exhibited linkage disequilibrium. Third, the three-locus A-C-G haplotype was associated with early-onset OCD.
CONCLUSIONS: The present study is the first to verify the associations of SNPs rs762178, rs1059004, and rs9653711 of the OLIG2 gene with OCD in a Chinese Han population. Thus, OLIG2 might serve as a potential target for OCD treatment in future studies. Further studies should verify the current findings.

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

OBJECTIVE: To study the clinicopathologic features, immunophenotype and histogenesis of dysembryoplastic neuroepithelial tumor (DNT).
METHODS: Fourteen cases of DNT were retrieved from the archival files of the Department. The histopathologic features and immunohistochemical findings were retrospectively studied. The long-term follow-up data were analyzed.
RESULTS: Eleven of the 14 cases studied were located in the temporal lobe. Histologically, the tumor consisted of a heterogeneous admixture of neuronal and glial cells (including 1 simple form case, 8 complex form cases and 5 non-specific form cases). The specific glioneuronal element was seen in 9 cases. Variable degrees of cortical dysplasia (CD) were found in 10 out of the 11 cases which had sufficient tissue samples for thorough histologic examination. The morphologic appearance of CD included the presence of heterotopic neurons in molecular layer and/or white matter (7 cases), persistent subpial granular cell layer (4 cases), dyslamination (10 cases) and cellular abnormalities. Immunohistochemically, the oligodendroglial-like cells expressed Olig2. Some of which were positive for nestin, MAP-2, neurofilament and glial fibrillary acidic protein, but negative for NeuN. Long-term follow up revealed that 12 patients had class I postoperative seizure and 2 patients had class II seizure. No tumor recurrence was detected.
CONCLUSIONS: DNT is frequently associated with CD. The morphologic diagnosis can be confirmed by immunohistochemical study using a panel of antibodies.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD.
OBJECTIVE: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone.
METHODS: Family-based association candidate gene study.
METHODS: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics.
METHODS: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD.
METHODS: Genotypes of single nucleotide polymorphism markers and related haplotypes.
RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008).
CONCLUSIONS: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.