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Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk‐factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH‐wildtype than in IDH‐mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high‐risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression‐free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta‐analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH‐mutant subtype. Moreover, we found that 1p/19qCodel/TP73low subgroup shared the most favorable OS, 1p/19qNon−codel/TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73‐related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT‐PCR, which was consistent with the previous analytical result, and TP73 high‐expression subgroup suffered worse PFS than TP73 low‐expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma., TP73 mRNA expression and DNA methylation profile can be a risk factor impacting the prognosis of WHO grade II/III glioma independently, or combining with current glioma molecular classification. Our work showed the significant potential of TP73 gene as a molecular characteristic for evaluating the malignancy and survival outcome of WHO grade II/III glioma.

Meningiomas are among the most common primary brain tumors. There is a growing need for novel ways of differentiating between benign (World Health Organization [WHO] grade I) and atypical (WHO grade II) meningiomas as well as for novel markers of the tumor's future behavior. A difference between glucose metabolism in atypical and benign meningiomas is well known. However, a significant correlation between the systemic metabolic status of the patient and the meningioma WHO grade has not yet been established. Our aim was to compare the WHO grades of intracranial meningiomas with the patient's HbA1c levels as a more reliable marker of the chronic systemic metabolic status than the fasting blood glucose value, which is usually looked at. We retrospectively analyzed 15 patients and compared their meningioma WHO grade with their preoperative HbA1c values. Our results show that patients with benign intracranial meningiomas have significantly lower HbA1c value. Conversely, patients with atypical intracranial meningiomas have higher HbA1c values. Furthermore, we showed that the proliferation factor Ki67 was statistically strongly correlated with the HbA1c value (p

We describe a case of WHO grade I transitional meningioma with rosettes in a 68-year-old woman. The rosettes were composed of meningothelial cells arranged around dense collagenous cores. Even though the presence of rosettes in tumors of the brain and spinal cord is an indication of neuronal or ependymal differentiation, they are also known to occur in tumors of other lineages. Rosette is an uncommon morphological pattern in meningiomas, with only few cases reported in the literature.

Tanycytic ependymoma is a rare variant of ependymoma which has a predilection for the spinal cord. It is a WHO grade II tumour with favourable outcome. Although squash cytology of ependymoma is well described, there is sparse literature available on squash cytomorphology of tanycytic variant. Here we present two cases of squash cytology of tanycytic ependymoma. In the first case the diagnosis of tanycytic ependymoma was considered. However, in the second case a diagnosis of usual ependymoma was offered. Subsequently histopathology confirmed tanycytic nature in both the cases. In this article we discuss the squash cytological features of tanycytic ependymoma along with its differential diagnosis. Diagn. Cytopathol. 2017;45:270-273. © 2016 Wiley Periodicals, Inc.

Purpose To determine whether the chemical shift of residual N-acetylaspartate (NAA) signal in pilocytic astrocytomas (PA) is consistent with the position of the NAA peak in controls. Methods MR spectra from 27 pediatric World Health Organization (WHO) grade I pilocytic astrocytoma patients, fifteen patients with WHO grade II and high-grade (III–IV) astrocytomas, and 36 controls were analyzed. All spectra were acquired with a short echo time (35 ms), single voxel point-resolved spectroscopy sequence on clinical 3 tesla scanners. Fully automated LCModel software was used for processing, which included the fitting of peak positions for NAA and creatine (Cr). Results The chemical shift difference between the NAA and Cr peaks was significantly smaller (by 0.016 ± 0.005 parts per million, P

We present two cases of atypical meningioma WHO grade II with a history of multiple local recurrences and late pulmonary metastases. Comparative cytogenetic analyses on 1p and 22q confirmed clonal origin of the primary intracranial meningiomas and the pulmonary metastases in both cases. These cases illustrate the importance of close neuroradiological follow-up to detect tumor recurrence in patients with atypical meningiomas WHO grade II even with clinically stable disease and should sensitize clinicians to late extracranial metastases of these tumors, especially to the lung. In an effort to elucidate common clinical features of metastatic meningiomas, especially to the lung, the literature was reviewed from 1995 to 2014, identifying a total of 45 published cases.

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Purpose To assess the value of combining susceptibility-weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted MRI (PWI) in assessing World Health Organization (WHO) grade for brain astrocytoma. Materials and Methods A total of 94 patients with pathologically confirmed astrocytomas underwent SWI and DSC scans. The evaluation included intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max. The receiver operating characteristic curve (ROC) was used to assess the efficacy of combining two sequences in astrocytoma grading. Results ITSS within astrocytomas showed significant correlations with rCBV max (r = 0.72; P < 0.01) and with tumor grades (r = 0.92; P < 0.01), and there was also a significant correlation between rCBV and tumor grade (r = 0.77; P < 0.001). The area under the ROC, SWI, PWI, SWI, and PWI, in differentiation of the grades II and III astrocytomas were 0.995, 0.942, and 1.000, respectively; identifying grades III and IV were 0.773, 0.919, and 0.978, respectively; and identifying high and low-grade astrocytomas were 0.999, 0.992, 1.000, respectively. Conclusion ITSS was useful for assessing the WHO tumor grade in this cohort of patients with astrocytoma. The combination of SWI and PWI may improve the diagnostic accuracy of astrocytoma grading. J. Magn. Reson. Imaging 2014;39:1569–1574. © 2013 Wiley Periodicals, Inc.

BACKGROUND: The use of crossmatch-compatible platelets (PLTs) improves posttransfusion corrected count increments (CCIs) in patients with alloimmune PLT refractoriness. However, few reports address the efficacy of utilizing this strategy for patients requiring intensive PLT transfusion therapy lasting several weeks to months. STUDY DESIGN AND METHODS: Medical records of patients with two or more PLT crossmatch assays performed between 2002 and 2010 were reviewed. All patients were refractory to random single-donor apheresis PLT units, defined as two consecutive 1-hour posttransfusion CCIs of less than 7500. A commercial solid-phase adherence assay was used for crossmatching. RESULTS: Seventy-one patients were included. A median of four crossmatch assays were performed per patient (range, 2-17). Mean percent reactivity in initial (58.6%) versus last (55.3%) crossmatch assay for each patient demonstrated no trend toward progressive alloimmunization (p = NS). A total of 738 crossmatched PLT units were administered with a mean ± standard deviation CCI of 7000 ± 7900 (n = 443 units with adequate 1-hr posttransfusion counts), a significant improvement over random PLTs (p

Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present a case of CCM with histologically aggressive appearance and clinically aggressive behavior. The tumor demonstrated rapid regrowth and brain metastasis. The histological progression from the ordinal CCM to the atypical area and higher MIB-1 index was observed. We assume that the short time of recurrence and metastasis may result from atypical histological features in our case. If the CCM has a histologically aggressive appearance as in our case, we suggest that postoperative adjuvant radiotherapy should be performed despite total resection of the tumor.

Gangliogliomas are rare CNS neoplasms mostly occuring in young adults and are usually assigned to WHO grade I. The few cases of WHO grade IV gangliogliomas were either primarily malignant glio-neuronal tumors or underwent malignant progression from other WHO grades after radiotherapy. Herein, we present the case of a now 47-year-old female patient presenting with a benign ganglioglioma and showing a tumor recurrence 2 years later with an anaplastic ganglioglioma, assigned to WHO grade IV, with malignant transformation in both glial and neuronal components. The presented case is the first reported low-grade ganglioglioma rapidly progressing to a WHO grade IV glio-neuronal tumor not being associated with radiotherapy and showing malignant transformation in both astroglial and neuronal tumor cell components.

Some WHO grade I intracranial meningiomas resected from the same sites and with the same quality of resection (Simpson's grading scale) recur, while others do not. The reasons for this variability in occurrence of recurrence have not yet been determined. We therefore investigated the prognostic recurrence value of seven biological markers on a series of completely resected WHO grade I meningiomas. For this purpose, we analysed a series of 33 WHO grade I meningiomas totally resected between 1980 and 1990 (a follow-up of 10 years), including 14 cases of recurrence. The fixed tumour material from each meningioma was submitted to histochemical analyses targeting galectin-3 and its binding sites, the S100A5, S100A6 and S100B proteins, and cathepsin-B and -D. The levels of expression were assessed semi-quantitatively (in terms of the staining intensity and the labelling index) and submitted to uni- and multivariate analyses. Of all the markers investigated, only S100A5 expression can be associated with any significant prognostic value in the matter of recurrence. More particularly, the meningiomas with high levels of S100A5 staining intensity either did not recur, or recurred later than those with a low immunopositive S100A5 intensity (P = 0.004). Cox regression analyses demonstrated that this latter marker was associated with significant prognostic values independent of the patients' ages. Furthermore, the combination of the patients' ages and S100A5 staining intensity permitted the identification of a group with a particularly high risk of recurrence, that is, the patients younger than 55 and with meningiomas exhibiting low S100A5 intensities (P = 0.001). In conclusion, the S100A5 protein could play a role in the recurrence of totally resected WHO grade I meningiomas.

Summary A cohort of 148 patients with papillary Ta-T1 transitional cell carcinomas (TCCs) was followed up for over 10 years and flow cytometric (DNAploidy, S phase fraction) and morphometric variables (5 nuclear factors, volume corrected mitotic index) were related to prognosis during this period. Recurrence-free survival was significantly related to DNAploidy, S phase fraction and M/V index. Progression in T-category was predicted by M/V index, S phase fraction, DNA ploidy and WHO grade. The same variables predicted progression in N- and M-categories. In a multivariate analysis only M/V index and S phase fraction were independent predictors of progression. Univariate analysis showed that M/V index, SPF, DNA ploidy and WHO grade predicted survival. In a multivariate survival analysis only M/V index and SPF were independent predictors. The results showed that proliferation indices had independent prognostic value in papillary Ta-T1 TCCs and the grading of these tumours could be based on the proliferation indices. Papillary Ta-T1 tumours with a M/V index value 10/mm2 or SPF 10% had a favourable prognosis whereas tumours with M/V index > 10/mm2 or SPF > 10% had a high malignant potential.

Combined tumors showing histologic features of both ependymoma and subependymoma have been described. In this report we present a case of combined tanycytic ependymoma with foci of subependymoma (WHO grade II), occurring in a 40 year-old male, which arose in the wall of the lateral ventricle. The tanycytic ependymoma component showed elongated fibrillary cells with a fascicular pattern of growth, while the subependymoma component showed clustered cell bodies surrounded by a fibrillary stroma with a microcystic appearance.We consider the present case to be an unusual example of tanycytic ependymoma; which to the best of our knowledge has not been associated with a subependymoma.

In most cases, theallelic losses involve loci along the entire chromosome, afinding in line with monosomy 10. LOH on chromosome 10may also be detected in anaplastic astrocytomas (WHO GradeIII) and diffuse astrocytomas (WHO Grade II), but is lesscommon than in glioblastomas and more frequently restrictedto partial losses.

Aim To evaluate methods to collect bleeding outcomes in thrombocytopenic patients, including by patient self-assessment, and to investigate the association between platelet count and bleeding. Methods Consecutive patients with haematological malignancies were enrolled in a study of bleeding data collection, platelet counts and transfusions during the period of thrombocytopenia. An educational session and information sheet was designed for patient self-assessment. Results A total of 19 patients were included in the study. 410 days of thrombocytopenia were eligible for assessment of bleeds. Self-assessment was deemed feasible, as self-assessment was successfully completed on 288/410 (70%) of thrombocytopenic days. There was 86% agreement between bleeding data collected by both self-assessment and medical examination, using a structured assessment form. Examples of discrepancies included the duration of petechiae/bruises and the reporting of minor bleeding. There was no evidence for an association between patients’ morning platelet count and daily WHO bleeding grade. Bleeding events were compared for platelet counts of ≤10 × 109 L−1, 11–20 × 109 L−1, and >20 × 109 L−1. The incidence of WHO Grade one and two bleeds were similar and did not reveal higher rates of bleeding at lower counts1. Conclusion Patient self-assessment can help support comprehensive daily prospective monitoring of bleeding, specifically facilitating data collection following hospital discharge. Exact definitions for bleeding events remains problematic. The association between platelet count, risk of bleeding and role of prophylactic platelet transfusions needs further evaluating in larger prospective trials. Reference 1Stanworth S.J., Dyer C, Casbard A & Murphy M. (2006) Vox Sang. 91 63–9