Susceptibility-Weighted MRI for Predicting NF-2 Mutations and S100 Protein Expression in Meningiomas.

S100 protein expression levels and neurofibromatosis type 2 (NF-2) mutations result in different disease courses in meningiomas. This study aimed to investigate non-invasive biomarkers of NF-2 copy number loss and S100 protein expression in meningiomas using morphological, radiomics, and deep learning-based features of susceptibility-weighted MRI (SWI). This retrospective study included 99 patients with S100 protein expression data and 92 patients with NF-2 copy number loss information. Preoperative cranial MRI was conducted using a 3T clinical MR scanner. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and subsequent registration of FLAIR to high-resolution SWI was performed. First-order textural features of SWI were extracted and assessed using Pyradiomics. Morphological features, including the tumor growth pattern, peritumoral edema, sinus invasion, hyperostosis, bone destruction, and intratumoral calcification, were semi-quantitatively assessed. Mann-Whitney U tests were utilized to assess the differences in the SWI features of meningiomas with and without S100 protein expression or NF-2 copy number loss. A logistic regression analysis was used to examine the relationship between these features and the respective subgroups. Additionally, a convolutional neural network (CNN) was used to extract hierarchical features of SWI, which were subsequently employed in a light gradient boosting machine classifier to predict the NF-2 copy number loss and S100 protein expression. NF-2 copy number loss was associated with a higher risk of developing high-grade tumors. Additionally, elevated signal intensity and a decrease in entropy within the tumoral region on SWI were observed in meningiomas with S100 protein expression. On the other hand, NF-2 copy number loss was associated with lower SWI signal intensity, a growth pattern described as "en plaque", and the presence of calcification within the tumor. The logistic regression model achieved an accuracy of 0.59 for predicting NF-2 copy number loss and an accuracy of 0.70 for identifying S100 protein expression. Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

A Rare Case of BRAF-mutated Metastatic Pleomorphic Xanthoastrocytoma Patient who Developed Radiodermatitis After Receiving Anti-BRAF Treatment.

Pleomorphic xanthoastrocytoma (PXA) is a rare type of grade 2 or 3 brain tumor that usually occurs in children and young adults. The standard treatment for PXA is maximally safe resection, usually with adjuvant radiation therapy, for high-grade tumors. BRAF V600E mutation is one of the most common molecular alterations in these tumors, with nearly 70% of cases carrying this mutation. Although BRAF inhibitors have shown promise in treating progressive or refractory disease, their use has been associated with various adverse effects, including radiodermatitis, which is a relatively common complication. This paper presents a case of a 16-year-old male patient with BRAF-mutated metastatic PXA, who developed mild radiodermatitis after receiving BRAF inhibitors with concurrent radiation therapy.

The parietooccipital interhemispheric transtentorial approach for pineal tumors.

Access to the pineal region has always been a challenge for neurosurgeons. The parietooccipital interhemispheric transtentorial approach is a slight variation of the traditional occipital transtentorial approach that provides adequate exposure to the lesions of the pineal region without introducing additional risks. In this study, the modified parietooccipital interhemispheric transtentorial approach is discussed including step-by-step anatomical cadaveric dissections and operative images. 27 adult patients (age > 18) who were operated over a 30-year period (1992-2022) by the senior author (M.N.P.) at two clinics, Marmara University, Department of Neurosurgery, Istanbul, Turkey and Acibadem Mehmet Ali Aydinlar University, Department of Neurosurgery, Istanbul, Turkey were analyzed. Only pineal region tumors were included in the analysis. Falcotentorial meningiomas and vascular lesions including cavernomas were excluded. 5 cadaveric specimens were dissected step by step following the surgical approach. Each step was documented using a Canon EOS 5D Mark II camera with Canon 100 mm Macro Lens. Step by step images of the dissections were presented including comparison with surgical images. Additional illustrations were used to describe the surgical corridor. The surgical corridor is maintained anterior to the parietooccipital sulcus along the medial of the precuneus. No retraction to the calcarine sulcus resulted in no postoperative hemianopsia. The neurovascular structures along the surgical corridor along with the nuances of the tentorium incision and splenium resection are discussed. The parietooccipital interhemispheric transtentorial approach provides a wide and safe corridor for surgical resection of pineal tumors.

Whole Transcriptome Sequencing Reveals Cancer-Related, Prognostically Significant Transcripts and Tumor-Infiltrating Immunocytes in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes.

Information theory approaches to improve glioma diagnostic workflows in surgical neuropathology.

AIMS: Resource-strained healthcare ecosystems often struggle with the adoption of the World Health Organization (WHO) recommendations for the classification of central nervous system (CNS) tumors. The generation of robust clinical diagnostic aids and the advancement of simple solutions to inform investment strategies in surgical neuropathology would improve patient care in these settings. METHODS: We used simple information theory calculations on a brain cancer simulation model and real-world data sets to compare contributions of clinical, histologic, immunohistochemical, and molecular information. An image noise assay was generated to compare the efficiencies of different image segmentation methods in H&E and Olig2 stained images obtained from digital slides. An auto-adjustable image analysis workflow was generated and compared with neuropathologists for p53 positivity quantification. Finally, the density of extracted features of the nuclei, p53 positivity quantification, and combined ATRX/age feature was used to generate a predictive model for 1p/19q codeletion in IDH-mutant tumors. RESULTS: Information theory calculations can be performed on open access platforms and provide significant insight into linear and nonlinear associations between diagnostic biomarkers. Age, p53, and ATRX status have significant information for the diagnosis of IDH-mutant tumors. The predictive models may facilitate the reduction of false-positive 1p/19q codeletion by fluorescence in situ hybridization (FISH) testing. CONCLUSIONS: We posit that this approach provides an improvement on the cIMPACT-NOW workflow recommendations for IDH-mutant tumors and a framework for future resource and testing allocation.

Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system.

OBJECTIVE: Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS: Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS: The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS: The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

Could gas-filled pseudocyst mimick extruded disc herniation?

There are case reports and small case series in the literature reporting gas-filled pseudocysts (GFP). However, a systematic review presenting overall view of the disease and its management is still lacking. In the present study, we aimed to make a systematic review of GFP cases, and present an exemplary case of ours. Our second aim was to discuss current theories for pathogenesis of GFP. A systematic review of GFP was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two large-scaled data search engines were used. A total of 53 articles were retrieved from the literature and presented with an exemplary case of ours. Mean age of the historical cohort was 59.47 years. There were 66 male (54.1%) and 56 female (45.9%) patients. The most prevalent clinical presentation was radicular sign/symptom in lower limbs with (29.1%) or without low back pain (LBP) (67%). Gas-filled pseudocyst has most commonly been diagnosed at the lower lumbar spine (L4-L5, 45.3%; L5-S1, 37.7%). Surgery was the treatment of choice in most of the patients (80%). In the whole cohort, 79.1% of the patients had complete recovery. Gas-filled pseudocysts are rarely observed in daily practice. They present mostly in men at the age of 60s. Precise differential diagnosis determination using appropriate imaging would help clinicians treat the patients properly. Gas-filled pseudocysts should be treated similarly to other spinal pathologies causing nerve root compression.

Neurosurgical follow-up and treatment of a series of 26 WHO grade III meningiomas.

Meningiomas are the most common primary intracranial tumors. They have three pathologic grades. Surgical resection aiming Simpson I resection is the standard treatment for meningiomas. Radiotherapy and Gamma Knife radiosurgery are the main adjuvant and salvage treatments. Chemotherapy has limited use. Grade II, and III meningiomas have a higher recurrence rate, and adjuvant radiotherapy is usually the standard treatment for grade III meningiomas. In this paper, we analyzed our meningioma series of 1401 patients and presented the treatment and follow-up results of 26 grade III meningioma cases. Median follow-up of grade III meningiomas was 40.5 (range, 1-154) months. The mean age of patients was 51.7 ± 15.7 years; 12 of them were female and 14 were male (female/male ratio = 0.9). The median progression-free survival (PFS) of them was 22 months, and overall survival (OS) was 62 months. Meningiomas with gross total resection (GTR), non-skull base meningiomas, and primary grade III meningiomas had longer PFS, while meningiomas with GTR, non-skull base meningiomas, and primary meningiomas had longer OS with a statistical significance.

Treatment and follow-up results of WHO grade II meningiomas.

Meningiomas are the most common primary intracranial tumors. They have three pathologic grades. Surgical resection aiming Simpson I resection is the standard treatment for meningiomas. Radiotherapy and Gamma Knife radiosurgery are the main adjuvant and salvage treatments. Chemotherapy has limited use. Grade II, and III meningiomas have a higher recurrence rate, and adjuvant radiotherapy is usually the standard treatment for grade III meningiomas but there is not a consensus regarding grade II meningiomas. In this paper, we analyzed our meningioma series of 1401 patients and presented the treatment and follow-up results of 170 grade II meningioma cases. The median follow-up of grade II meningiomas was 61 (range = 1-231) months. The mean age of patients was 52.5 ± 15.0 years, 102 of them were female and 68 were male (female/male ratio = 1.5). The median progression-free survival (PFS) of them was 109 months, and the cumulative overall survival (OS) rate was 85% at 10 years. Meningiomas with gross total resection, non-skull base meningiomas, and primary grade II meningiomas had longer PFS with statistical significance, while non-skull base meningiomas, younger group of patients, and primary grade II meningiomas had longer OS with a statistical significance.

Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma.

BACKGROUND: In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. METHODS: The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. RESULTS: The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14-33) variants per patient was reported. There was a median of 6 (0-590) reported somatic short variants per tumor. A median of 19 (0-94) broad SCNAs and a median of 6 (0-12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). CONCLUSIONS: We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

Identification of IDH and TERTp mutation status using 1 H-MRS in 112 hemispheric diffuse gliomas.

BACKGROUND: There is a growing interest in noninvasively defining molecular subsets of hemispheric diffuse gliomas based on the isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutation status, which correspond to distinct tumor entities, and differ in demographics, natural history, treatment response, recurrence, and survival patterns. PURPOSE: To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (1 H-MRS) at 3T can be used for noninvasive molecular classification of IDH and TERTp mutation-based subsets of gliomas. STUDY TYPE: Retrospective. SUBJECTS: In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years). FIELD STRENGTH/SEQUENCE: Short-TE 1 H-MRS (repetition time (TR) = 2000 msec, TE = 30 msec, number of signal averages = 192) and routine clinical brain tumor MR protocols were acquired at 3T. ASSESSMENT: 1 H-MRS data were quantified using LCModel software. TERTp and IDH1 or IDH2 (IDH1/2) mutations in the tissue were determined by either minisequencing or Sanger sequencing. STATISTICAL TESTS: Metabolic differences between IDH mutant and IDH wildtype gliomas were assessed by a Mann-Whitney U-test. A Kruskal-Wallis test followed by a Tukey-Kramer test was used to analyze metabolic differences between IDH and TERTp mutational molecular subsets of gliomas. A Spearman rank correlation coefficient was used to assess the correlations of metabolite intensities with the Ki-67 index. Furthermore, machine learning was employed to classify the IDH and TERTp mutational status of gliomas, and the accuracy, sensitivity, and specificity values were estimated. RESULTS: Short-TE 1 H-MRS classified the presence of an IDH mutation with 88.39% accuracy, 76.92% sensitivity, and 94.52% specificity, and a TERTp mutation within primary IDH wildtype gliomas with 92.59% accuracy, 83.33% sensitivity, and 95.24% specificity. DATA CONCLUSION: Short-TE 1 H-MRS could be used to identify molecular subsets of hemispheric diffuse gliomas corresponding to IDH and TERTp mutations. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1799-1809.

Elderly Patients with Intracranial Meningioma: Surgical Considerations in 228 Patients with a Comprehensive Analysis of the Literature.

BACKGROUND: Improved life expectancy and advanced diagnostic tools including computed tomography and magnetic resonance imaging have increased the awareness and diagnosis of intracranial meningiomas in the elderly population. The risk/benefit ratio of surgery in elderly patients with intracranial meningioma has not been clearly defined because of the lack of objective measurement tools. We aimed to understand the risk factors associated with postsurgical outcomes and how these risk factors affected postsurgical outcomes in elderly patients with intracranial meningioma. METHODS: We retrospectively evaluated 1372 patients, who were operated on for intracranial meningioma, using our prospectively collected database. The same senior author operated on all patients at 2 different tertiary clinics. Patients' clinical charts, presurgical postcontrast T1-weighted magnetic resonance images, operative reports, and pathology reports were reviewed. The relevant literature was also reviewed. RESULTS: Higher age, higher American Society of Anesthesiologists class, presence of comorbidities, tumor location, larger initial tumor size, and presence of peritumoral edema were all associated with postsurgical complications in elderly patients with intracranial meningioma. Age ≥50 years was the strongest predictor of postsurgical systemic complications, whereas higher American Society of Anesthesiologists class was the strongest predictor of postsurgical neurologic complications. A literature review showed higher morbidity and mortality of elderly patients with intracranial meningioma. Initial tumor size and postsurgical MIB-1 labeling index were higher in the elderly patients, both of which were predictors of tumor growth. CONCLUSIONS: Even though elderly patients operated on for intracranial meningioma had higher morbidity and mortality compared with younger patients, surgery is still much more beneficial than wait-and-see strategy in elderly patients.

Prognostic Factors in Elderly Patients with Diffuse Large B-Cell Lymphoma and Their Treatment Results

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.

Detection of the differences in the apparent diffusion coefficient values in different histopathological types of malignant breast lesions and comparison of cellular region/ stroma ratio and histopathological results

Background/aim: This study aimed to compare the apparent diffusion coefficient (ADC) values of malignant breast lesions with different histopathological types on diffusion-weighted imaging (DWI) and the cellular region/stroma (CR/S) ratio and histopathological results. Materials and methods: Breast diffusion-weighted magnetic resonance findings of 59 patients were retrospectively analyzed for malignant breast lesions. The CR/S ratio was calculated using breast wide-excisional biopsy or mastectomy specimens. Results: Receiver operating characteristic analysis was performed for malignant lesions and subtypes. An ADC threshold of 1.260 × 10 ­3 mm 2 /s was set to detect invasive ductal carcinoma with 80.8% sensitivity and 81.4% specificity. An ADC threshold of 1.391 × 10 ­3 mm 2 /s was set to detect invasive lobular carcinoma lesions with 88.2% sensitivity and 79.5% specificity. The ADC value for lesions with low CR/S ratio (n = 21) was 1.135 ± 0.429 × 10 ­3 mm 2 /s and it was 1.155 ± 0.429 × 10 ­3 mm 2 /s in the high CR/S ratio group (n = 18). Conclusion: ADC value calculation does not seem to be used as an alternative for histopathological detection, which is the gold standard for the differentiation of subtypes of malignant breast cancer. In addition, since there is a positive correlation between CR/S ratio and ADC values, it may be a strong marker to evaluate the stromal component of lesions.