MAPK pathway alterations in polymorphous low-grade neuroepithelial tumor of the young: diagnostic considerations.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently recognised tumor type with indolent behaviour with characteristic imaging and histomolecular features. We describe the clinical, imaging, histo-molecular features of 15 cases diagnosed as low-grade glioma suggestive of PLNTY, over a period of 3 years. Immunohistochemistry (IHC) and fluorescence in situ hybridisation were used to assess molecular alterations. The tumors were seen predominantly in children (range 5-65 years). Most of the patients presented with history of seizures. Imaging revealed cortical-subcortical well demarcated solid-cystic tumor with intratumoral calcification. Histopathology revealed a low-grade tumor with oligodendroglia-Iike cells admixed with astrocytic cells immunopositive for CD34. BRAF p.V600E mutations and FGFR2 breakapart were observed in six cases each, while three showed FGFR3 breakapart. FGFR2 breakapart positive PLNTY were seen in children exclusively. The majority of cases were seizure free post-surgery, except two patients who succumbed to the illness. PLNTY, needs to be considered as a prime differential diagnosis in a solid-cystic tumor in a young patient with history of seizures. Characteristic clinical features, radiology, histomorphology with an IHC panel of OLIG2, GFAP and CD34 correlates with one of the MAPK alterations in PLNTY (BRAF p.V600E, FGFR2/3 gene rearrangement). In a resource limited setting, this limited panel may be sufficient for a correlative diagnosis.

DNA Methylation in Recurrent Glioblastomas: Increased TEM8 Expression Activates the Src/PI3K/AKT/GSK-3ß/B-Catenin Pathway.

BACKGROUND/AIM: Glioblastomas (GBM) are infiltrative malignant brain tumors which mostly recur within a year's time following surgical resection and chemo-radiation therapy. Studies on glioblastoma cells following radio-chemotherapy, have been demonstrated to induce trans-differentiation, cellular plasticity, activation of DNA damage response and stemness. As glioblastomas are heterogenous tumors that develop treatment resistance and plasticity, we investigated if there exist genome-wide DNA methylation changes in recurrent tumors. MATERIALS AND METHODS: Utilizing genome-wide DNA methylation arrays, we compared the DNA methylation profile of 11 primary (first occurrence) tumors with 13 recurrent (relapsed) GBM, to delineate the contribution of epigenetic changes associated with therapy exposure, therapy resistance, and relapse of disease. RESULTS: Our data revealed 1,224 hypermethylated- and 526 hypomethylated-probes in recurrent glioblastomas compared to primary disease. We found differential methylation of solute carrier and ion channel genes, interleukin receptor/ligand genes, tumor-suppressor genes and genes associated with metastasis. We functionally characterized one such hypomethylated-up-regulated gene, namely anthrax toxin receptor 1/tumor endothelial marker 8 (ANTXR1/TEM8), whose expression was validated to be significantly up-regulated in recurrent glioblastomas compared to primary tumors and confirmed by immunohistochemistry. Using overexpression and knockdown approaches, we showed that TEM8 induces proliferation, invasion, migration, and chemo-radioresistance in glioblastoma cells. Additionally, we demonstrated a novel mechanism of ß-catenin stabilization and activation of the ß-catenin transcriptional program due to TEM8 overexpression via a Src/PI3K/AKT/GSK3ß/ß-catenin pathway. CONCLUSION: We report genome-wide DNA methylation changes in recurrent GBM and suggest involvement of the TEM8 gene in GBM recurrence and progression.

Thalamic H3K27M altered diffuse midline gliomas: Clinicopathological and outcome analysis.

INTRODUCTION: Diffuse midline glioma (DMG) is a relatively new entity which was introduced in the fourth edition of the WHO classification of CNS tumours in 2016 and later underwent revision in 2021. It is an infiltrative glioma arising from midline structures, viz., thalamus, spine, and brainstem. Current literature on DMG is based majorly on brainstem lesions, and DMGs arising elsewhere remain unexplored. In our study, we have discussed our experience with thalamic DMGs. METHODOLOGY: This is a retrospective observational study of all patients with histopathologically proven DMG H3K27M altered, arising in the thalamus from 2018 to 2022. Clinical, neuroimaging, and pathology were re-reviewed, and prognostic factors for 3 months, 6 months, and overall survival (OS) were analyzed for all patients. RESULTS: There were 89 patients- 64 adults and 25 pediatric patients with thalamic DMG. The median age at presentation was 24 years. Raised ICP followed by limb weakness were the most common presenting complaints. Stereotactic biopsy was performed in 64 (71.9 %) patients and surgical decompression in 25 (28.1 %) patients. CSF diversion was required in 53 (59.6 %) patients. Median survival was 8 months in adults and 7 months in pediatric (p-value: 0.51). Raised ICP and TP53 mutation were prognostic factors in pediatric population. Radiotherapy with or without chemotherapy improved survival (p-value- <0.01). CONCLUSION: Thalamic DMGs have a poor prognosis which is comparable to brainstem DMGs. Radiotherapy improves survival in these patients. However, the disease remains an enigma and further work delving into its molecular characterization should be encouraged.

Prospective Study to Evaluate the Role of Dual Point Contrast-enhanced Magnetic Resonance Imaging in Differentiation of Brain Tumoral from Nontumoral Tissue: A Magnetic Resonance/PET Study.

Background and Purpose: Follow-up imaging of gliomas is crucial to look for residual or recurrence and to differentiate them from nontumoral tissue. Positron emission tomography (PET)-magnetic resonance imaging (MRI) is the problem-solving tool in such cases. We investigated the role of dual point contrast (DPC)-enhanced MRI to discriminate tumoral from the nontumoral tissue compared to PET-MRI taken as the gold standard. Materials and Methods: The institutional ethics committee approved the study, and consent was obtained from all the patients included in the study. We prospectively did immediate and 75-min delayed contrast MRI in glioma cases who came for follow-up as a part of PET-MRI study in our institute. Subtracted images were obtained using immediate and 75-min delayed contrast images. Color-coded subtracted images were compared with PET-MRI images. 75-min delayed contrast MRI and diffusion-weighted imaging (DWI) images with Gray Scale inversion were compared with PET attenuation-corrected images. Results: We included 23 PET MRI cases done with different radiotracers in our study. Overall, we found PET-DPC correlation in (20/20 ~ 100%) cases of enhancing tumors. In two cases (DOPA and fluorodeoxyglucose), since they were nonenhancing low-grade gliomas and the other one was melanoma with intrinsic T1 hyperintensity and the DPC technique could not be used. DWI-PET correlated in 17/19 (~89.4%) cases, and perfusion-weighted imaging (PWI)-PET dynamic susceptibility contrast (DSC)/ASL correlated in 14/18 (~77.7%) cases after cases with hemorrhage were excluded. Conclusion: DPC MRI showed a good correlation with PET MRI in discriminating tumoral from the nontumoral tissue. DPC MRI can act as a potential alternative to PET MRI in peripheral hospitals where PET is not available. However, the DPC technique is limited in low-grade nonenhancing gliomas.

Safety and Efficacy of Biopsy in Patients with Diffuse Intrinsic Pontine Gliomas.

BACKGROUND: Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies. METHODS: This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques. RESULTS: A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality. CONCLUSIONS: Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy.

Prognostic Factors and Outcomes in World Health Organization Grade 1 and Grade 2 Intracranial Meningiomas-5-Year Institutional Experience.

BACKGROUND: Meningiomas are the most frequent primary intracranial tumor. While histological grade and grade of excision are established predictors of recurrence, the predictive ability of other clinical features, such as the role of radical excision of dural attachment and postoperative radiation therapy in intermediate-risk groups, remains unknown. METHODS: Clinical and radiological features and surgical details were analyzed in 451 World Health Organization (WHO) grade 1 intracranial meningiomas and 248 WHO grade 2 meningiomas operated on between 2010 and 2015. Outcomes were assessed in 352 WHO grade 1 and 208 WHO grade 2 meningiomas, studying the effect of extent of resection and use of radiation therapy. Kaplan-Meier analysis was used to determine differences in survival by extent of resection and use of postoperative radiation therapy in the treatment of the meningiomas. RESULTS: The mean age of the cohort was 46.3 years, with a female predominance. On univariate analysis, sex, WHO grade, and Simpson grade were significant predictors of recurrence. On multivariate analysis, WHO grade and Simpson grade remained significant predictors of recurrence. Recurrence was significantly associated with poor performance status and mortality. Postoperative radiation significantly improved progression-free survival among patients with grade 2 meningiomas who underwent gross total resection, but not among patients with grade 1 and grade 2 meningiomas who underwent subtotal resection. CONCLUSIONS: WHO grade and Simpson grade are independent predictors of recurrence in meningiomas. Regardless of WHO grade, gross total resection must be performed when possible, and postoperative radiation therapy may be recommended in grade 2 meningiomas.

Evaluating the Diagnostic Efficacy of 99mTc-Methionine Single-Photon Emission Computed Tomography-Computed Tomography: A Head-to-Head Comparison with 11C-Methionine Positron Emission Tomography-Magnetic Resonance Imaging in Glioma Patients.

Background: Amino acid positron emission tomography (PET) imaging plays a significant role in the diagnosis of gliomas and in differentiating tumor recurrence from necrosis. In this study, the authors evaluated the diagnostic efficacy of [99mTc]Tc-methionine single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with [11C]methionine PET-magnetic resonance imaging (MRI) in delineating tumors. Methods: Thirty-one (primary: 16 and postoperative: 15) patients of confirmed (either MRI or histopathological proven) glioma underwent both [99mTc]Tc-methionine SPECT-CT and [11C]methionine PET-MRI. A comparative analysis was performed between SPECT, PET, and MR images to calculate the concordance between the modalities and to evaluate the diagnostic efficacy of the [99mTc]Tc-methionine SPECT. Results: [99mTc]Tc-methionine SPECT showed comparable uptake in the tumor lesions in comparison to [11C]methionine PET. A significant and strong positive correlation was observed between the volume of tumor (Vt) in PET and Vt MR (p < 0.004). Likewise, a significant and strong positive correlation was found between Vt SPECT and Vt MR. [99mTc]-methionine has a sensitivity and specificity of 91% and 75%, respectively, compared with 82% and 100% for [11C]methionine in postoperative cases to differentiate the tumor recurrence from necrosis. The sensitivity and specificity of [99mTc]Tc-methionine was 92% and 100%, respectively, compared with 92% and 67% for [11C]methionine in primary tumors. Conclusion: [99mTc]Tc-methionine SPECT-CT is as equally good as [11C]methionine for diagnosing and differentiating it from necrosis especially in high-grade glioma.

Glioblastoma with Probable Intratumoral Adenocarcinoma Metastasis: A Rare Report with Review of Literature.

"Tumor-to-tumor metastasis," an uncommon phenomenon, refers to a primary tumor metastasis into another tumor, with the most frequent donor being lung carcinoma and common recipients being renal cell carcinoma and meningioma. Tumor-to-tumor metastasis occurring in gliomas is rare with less than 20 reports described so far, and that into a glioblastoma is even rarer. We report a 54-year man, diagnosed with glioblastoma, IDH-wildtype, with metastasis of an adenocarcinoma into it. On histomorphology, the glial component was composed of astrocytic cells and showed increased mitosis, microvascular proliferation, and focal necrosis. This was intermingled with an adenocarcinomatous tumor with pleomorphic epithelial cells in glands, nests, and sheets. On immunohistochemistry, the adenocarcinomatous areas were positive for AE1/AE3 and TTF1 but negative for glial markers, ruling out adenoid glioblastoma. Further cytogenetic analysis showed EGFR amplification in the glial component but not in the adenocarcinoma component, ruling out glioblastoma with true epithelial metaplasia, and supporting the diagnosis of adenocarcinoma metastasis into glioblastoma. Glioblastomas may be susceptible to intratumoral metastasis due to the proliferating leaky vascular channels, however, the short survival of patients with glioblastoma may be responsible for the rarity of this occurrence. The documentation of these tumors is important as they may be important for clinical diagnosis and further treatment and prognosis.

Glioma arising in the setting of mismatch repair deficiency-rare or are we missing it?

Germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) can be mono-allelic or biallelic, resulting in a Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD) syndrome respectively. Glioma arising in the setting of MMR deficiency is uncommon. We describe two pediatric patients with high-grade glioma (HGG) and associated MMR protein deficiency. On histomorphology both cases showed HGG with astrocytic morphology and prominent multinucleated tumor cells. On immunohistochemistry, the first case was negative for IDH1 p.R132H showed loss of ATRX and p53 positivity. The second case was positive for IDH1 p.R132H and p53, but showed retained expression of ATRX. The histomorphology in both cases and additionally IDH mutation with retained ATRX in the second case, prompted us to test for MMR protein deficiency which was carried out by immunohistochemistry (IHC). One case revealed an immunostaining pattern suggestive of CMMRD while the other was suggestive of LS. Both the cases showed good response to surgery and radio-chemotherapy in the follow-up available. Our cases highlight the importance of testing for MMR proteins by simple IHC, in the setting of appropriate clinical scenario, histopathological and immunohistochemical findings. The recognition of these tumors is extremely important to guide further treatment and prompt family screening.

MYCN amplification in spinal ependymoma: A five-year retrospective study.

Spinal ependymoma with MYCN amplification is a newly recognized type of spinal ependymoma that is known to be associated with poor prognosis. Available studies on this relatively rare tumor type have observed that these tumors tend to disseminate along the spinal cord and behave aggressively with worse overall and progression-free survival compared to the other types of ependymoma. In this study, we describe the clinical and histopathological features of spinal ependymomas in a single institution cohort with emphasis on those with MYCN amplification.

IRX1 is a novel gene, overexpressed in high-grade IDH-mutant astrocytomas.

BACKGROUND: IDH-mutant astrocytomas include CNS WHO grade 2 (A2), grade 3 (A3) and grade 4 (A4), of which A3 and A4 are high-grade. A3 has a heterogenous clinical outcome that cannot be explained entirely by the existing molecular biomarkers. We comprehensively studied the transcriptome profile of A3 to determine clinical significance. METHODS: TCGA mRNA-sequencing data of A3 was analyzed to derive differentially expressed genes (DEG), which were short-listed using various approaches. mRNA expression of the short-listed genes was validated using NanoString platform on a uniformly treated and molecularly characterized A3 cohort. Protein expression of one prognostically significant gene, Iroquois-class homeodomain (IRX1) was assessed by immunohistochemistry and correlated with patient survival and tumor recurrence. IRX1 expression was also studied in different grades of astrocytoma. Since DNA methyltransferase 3 alpha (DNMT3A) influences IRX1 expression, its mutations were evaluated in a subset of tumors. RESULTS: TCGA analysis identified 96 DEG in A3 tumours. 57 genes were short-listed and finally narrowed down to 14 genes. mRNA values of 12/14 genes validated in our cohort. On multiple-variable analysis, IRX1 was the most prognostically relevant gene, with respect to progression free survival of patients. Further, IRX1 immunoexpression was significantly higher in A3 and A4 when compared to A2 and glioblastoma. Higher IRX1 immunoexpression correlated with poor prognosis in patients with A3 tumours. Also, a higher IRX1 expression was associated with DNMT3A mutation. CONCLUSION: Our study identifies IRX1 as a novel biomarker overexpressed in high-grade IDH-mutant astrocytomas with prognostic significance in A3. DNMT3A mutation probably modulates IRX1 expression.

Primary Intracranial Alveolar Soft Part Sarcoma: A Report of 3 Cases.

Alveolar soft part sarcoma (ASPS) commonly involves extremities and head and neck regions. Primary intracranial ASPS is rare. We report a series of 3 primary intracranial ASPS. These were not suspected clinically and histopathology with immunohistochemistry proved to be diagnostic in all 3 tumors.

Chitinase 3-Like 2.

OBJECTIVES: We aimed to evaluate the expression pattern of chitinase 3-like 2 (CHI3L2) in the tumor core and peritumoral brain zone (PBZ) of newly diagnosed glioblastoma (GBM) in recurrent tumors and its association with patient prognosis. METHODS: The study was conducted on three sample sets derived from different patient cohorts. Messenger RNA (mRNA) expression of CHI3L2 in the tumor core and PBZ (n = 34) compared with control (n = 20) tissues was studied by quantitative polymerase chain reaction in sample set 1. Sample set 2 included 19 paired, primary-recurrent GBM tissues. Sample set 3 comprised 82 GBM tissues of patients with treatment and follow-up information. Immunohistochemistry (IHC) was performed on all three sample sets. RESULTS: mRNA expression of CHI3L2 was significantly higher in the tumor core and PBZ compared with control (P < .0001). By IHC, CHI3L2 showed strong cytoplasmic staining in tumor cells. Recurrent tumors had a higher expression of CHI3L2 compared with primary tumors (P = .007). Survival analysis showed CHI3L2 expression was associated with shorter overall survival (P = .034) and progression-free survival (P = .010), which was in line with The Cancer Genome Atlas cohort (P = .043). CONCLUSIONS: High expression of CHI3L2 in the tumor core and PBZ, as well as its association with tumor recurrence and poor patient prognosis, suggests it might be contributing to tumor spread and recurrence.

Gamut of Orbital Lesions in a Tertiary Neurocenter-A Clinicopathological Study of Lesions Seen Over a Period of One Decade.

Background: The orbital region is an anatomically complex area comprising crucial contiguous/adjacent structures. Since the eye has a neuroectodermal basis of embryogenesis, many of the lesions may be similar to those arising in the central nervous system. Objective: To record and describe the clinicopathological spectrum of orbital lesions presenting to a neurology center. Study Setting: The retrospective study included biopsy/resected specimens of patients with orbital/ophthalmic lesions referred to the Department of Neuropathology, between February 2007 and February 2018. Materials and Methods: : The demographic, clinical, and radiological details were retrieved from the departmental archives and the slides were reviewed. Results: There were 99 cases in the period of the study (2007-2018) with a peak in fourth and fifth decades (age range: 5 months to 68 years; mean: 37.2 years; M: F =1.06: 1). Eighty-six (86.8%) cases had epicenter in the orbit, whereas 13 (13.13%) cases were extraorbital with orbital extension. The benign neoplasms predominated (50/99, 50.5%) followed by malignant neoplasms (24/99, 24.24%), infective conditions (11/99, 11.11%) and tumor like conditions (7/99, 7.07%). The most common benign tumor was vascular tumor (17/50, 34%) followed by meningioma (12/50, 24%), while epithelial malignant tumor (6/24, 25%) was the most common malignancy. Fungal infection was the most frequent infective condition (6/11, 54.5%). Conclusion: The spectrum of ocular-orbital lesions varies with the geographic area and the nature of the institute catering to the needs of patients. The spectrum of lesions that we encountered from a neurological institute was vastly different from that reported from ophthalmic centers with very low frequency of retinoblastomas.

A review of adult-type diffuse gliomas in the WHO CNS5 classification with special reference to Astrocytoma, IDH-mutant and Oligodendroglioma, IDH-mutant and 1p/19q codeleted.

The fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5) features several changes in the classification, diagnostic criteria, nomenclature, and grading of diffuse gliomas. Adult-type diffuse gliomas are genetically defined and include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype. This review briefly discusses two tumor types: astrocytoma, IDH-mutant, and oligodendroglioma, IDH-mutant and 1p/19q codeleted, with emphasis on relevant changes in their classification and defining molecular genetic alterations. A simplified approach to the diagnosis of these tumors is provided.

Diffuse intrinsic pontine gliomas in adults: A retrospective study.

Background: Brainstem gliomas (BSG) constitutes very small proportion in adults brain tumors with pons as most common location. There is significant paucity in literature for adult diffuse intrinsic pontine gliomas (DIPG). Objective: In this study, we attempt to review the outcomes of DIPG in single institute. Methods: We performed a retrospective chart review of adult DIPG from last 8 years (2010-2018) in a tertiary institute. DIPG was defined as expansile lesions involving more than 50% of the greatest diameter in the pons. Results: We found a total 46 patients with the diagnosis of adult BSG. Based on the definition, 23 patients with adult DIPG qualified to be included in the study. The median age was 32 years (IQR: 22-41), with a sex ratio of 16/7 (M/F). Cranial palsies were found in 17 (73%) patients. The median duration of symptoms was 6 months. On magnetic resonance imaging (MRI), contrast enhancement was found in seven (30%) patients. Biopsy was done in five patients. Median follow up was 11 months (IQR: 7-15). Median overall survival (OS) was 15 months (95%, CI 8.3-21.6). Fourteen patients had succumbed to death at the latest follow-up, and seven patients were alive. Median OS for the patients with age less than 40 years and more than 40 years was 7 and 22 months, respectively (p = 0.016). Rest of the variables did not effect OS significantly. Conclusion: Adult DIPG's significantly differs from pediatric counterparts in clinical characteristics, as well as OS. Age was the only factor which was significantly associated with survival in our study. Long-term studies with molecular profiling may help in further characterizing these lesions.

Pathological Spectrum of Dura-Based Nonmeningothelial Lesions: 5 Years' Experience from a Tertiary Care Centre.

Introduction Nonmeningothelial lesions arising from the dura comprise a wide spectrum of pathologies ranging from neoplastic to infective etiologies. They have overlapping clinical and radiologic findings necessitating histopathological evaluation for the final diagnosis which in turn dictates management and prognosis. Therapeutic strategies are different for each of the lesion. There is scarcity of large case series detailing clinicopathological spectrum of dura-based nonmeningothelial lesions. Materials and Methods In this study, we analyzed the neuropathological spectrum of dura-based nonmeningothelial lesions diagnosed over a period of 5 years in our tertiary care center. Results There were 79 cases of dura-based nonmeningothelial lesions constituting 7.3% of all dura-based lesions (age range: 2-75 years; M:F = 2:3). Basal region was more frequently involved than the convexities. On histopathology, neoplastic lesions predominated (92.4%) and included in order of frequency solitary fibrous tumor/hemangiopericytoma (35.6%), gliomas (27.4%), metastasis (27.4%), mesenchymal tumors (4%), primitive neuroectodermal tumor (2.73%), and medulloblastoma (2.73%). Infective lesions were less frequent (7.6%), included fungal infections and Rosai-Dorfman disease. Conclusion Awareness of the spectrum of nonmeningothelial dural lesions is useful for pathologists as well as the treating surgeon.

Spinal astroblastoma: a rare tumour in an unusual location.

Astroblastomas are central nervous system tumours with unknown cell of origin and clinical behaviour. These tumours occur most commonly in cerebral hemispheres with spinal astroblastomas being very rare. We report a case of spinal astroblastoma which harboured MN1 alteration.

Diffusion and perfusion imaging biomarkers of H3 K27M mutation status in diffuse midline gliomas.

PURPOSE: H3K27M-mutant diffuse midline gliomas (M-DMGs) exhibit a clinically aggressive course. We studied diffusion-weighted imaging (DWI) and perfusion (PWI) MRI features of DMG with the hypothesis that DWI-PWI metrics can serve as biomarkers for the prediction of the H3K27M mutation status in DMGs. METHODS: A retrospective review of the institutional database (imaging and histopathology) of patients with DMG (July 2016 to July 2020) was performed. Tumoral apparent diffusion coefficient (ADC) and peritumoral ADC (PT ADC) values and their normalized values (nADC and nPT ADC) were computed. Perfusion data were analyzed with manual arterial input function (AIF) and leakage correction (LC) Boxerman-Weiskoff models. Normalized maximum relative CBV (rCBV) was evaluated. Intergroup analysis of the imaging variables was done between M-DMGs and wild-type (WT-DMGs) groups. RESULTS: Ninety-four cases (M-DMGs-n = 48 (51%) and WT-DMGs-n = 46(49%)) were included. Significantly lower PT ADC (mutant-1.1 ± 0.33, WT-1.23 ± 0.34; P = 0.033) and nPT ADC (mutant-1.64 ± 0.48, WT-1.83 ± 0.54; P = 0.040) were noted in the M-DMGs. The rCBV (mutant-25.17 ± 27.76, WT-13.73 ± 14.83; P = 0.018) and nrCBV (mutant-3.44 ± 2.16, WT-2.39 ± 1.25; P = 0.049) were significantly higher in the M-DMGs group. Among thalamic DMGs, the min ADC, PT ADC, and nADC and nPT ADC were lower in M-DMGs while nrCBV (corrected and uncorrected) was significantly higher. Receiver operator characteristic curve analysis demonstrated that PT ADC (cut-off-1.245), nPT ADC (cut-off-1.853), and nrCBV (cut-off-1.83) were significant independent predictors of H3K27M mutational status in DMGs. CONCLUSION: DWI and PWI features hold value in preoperative prediction of H3K27M-mutation status in DMGs.

Granular Cell Tumor and Spindle Cell Oncocytoma of the Pituitary Gland: Imaging and Intraoperative Cytology Diagnostic Dilemmas and Management Challenges.

BACKGROUND: Tumors arising from the posterior pituitary gland are rare and closely resemble pituitary adenoma in presentation and imaging. Most of them come as a histopathologic surprise. We have analyzed the posterior pituitary tumors managed in our institute and have discussed the dilemmas in imaging, challenges in intraoperative squash cytology, and surgical management. METHODS: We retrospectively reviewed our operative database of pituitary tumors over the past 10 years, which included five posterior pituitary tumors (three granular cell tumors [GCTs] and two spindle cell oncocytomas [SCOs]). Clinical, imaging, and endocrine characteristics; intraoperative details; histopathologic features; and postoperative outcomes were collected and analyzed. RESULTS: The mean age of the patients was 47 years. All patients presented with varying degrees of vision loss. Radiology revealed a sellar / suprasellar lesion with the pituitary gland seen separately in two of three GCTs, whereas a separate pituitary gland could not be identified in both the SCOs. Pituitary adenoma was a radiologic diagnosis in only two of five cases. Three patients underwent a transsphenoidal surgery, whereas two underwent surgery by the transcranial approach. Intraoperative cytology was challenging, though a possibility of posterior pituitary tumor was considered in three of four cases, whereas one was considered meningioma. All the tumors were very vascular and influenced the extent of resection. CONCLUSIONS: GCTs and SCOs are relatively uncommon tumors that are difficult to diagnose on preoperative imaging. Intraoperative squash cytology too can pose challenges. A preoperative suspicion can prepare the surgeon for surgery of these hypervascular tumors. The transcranial approach may be necessary in cases of uncertainty in imaging.