Characterization of neurodegenerative pathologies in adult and pediatric subjects with Down syndrome.

BackgroundDown syndrome (DS) is frequently associated with Alzheimer's disease neuropathologic change (ADNC). However, studies assessing the full spectrum of neurodegenerative pathologies using modern consensus and staging criteria remain limited.ObjectiveWe aimed to elucidate the progression of neurodegenerative pathologies in DS and to explore the prevalence of comorbid pathologies across a broad age range (0-76 years), using comprehensive neuropathological assessments.

Microenhancement as a Biomarker for Cerebral Microbleed in Inflammatory Cerebral Amyloid Angiopathy: Insights From 3D T1 Black-Blood MR Imaging.

Objectives: Cerebral microbleeds (cMBs) are common imaging findings in conditions related to cerebral amyloid angiopathy (CAA). Blood-brain barrier (BBB) leakage is considered pivotal in their pathogenesis. This study investigates the potential role of cerebral microenhancement (cME) as an imaging biomarker on 3D T1 black-blood MRI (BB-MRI) for BBB rupture, predicting the formation of cMBs in inflammatory CAA variants.

Surgical Management of a Massive Frontal Bone Hemangioma: Case Report.

Intraosseous hemangiomas are rare, benign tumors that can arise from the calvarium. These lesions often invade the outer table of the skull, but typically spare the inner table and intracranial structures. En bloc surgical resection is the standard treatment for intraosseous hemangiomas.

Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management.

Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients.

Distant Pituitary Adenoma Spread: A Systematic Review and Report of 2 Cases.

Background: Distant spread of pituitary adenoma outside the sellar/suprasellar region is classified as pituitary carcinoma. Cerebrospinal fluid (CSF)-born spread of pituitary adenoma can occur after tumor cell spillage into the CSF space after surgery, irradiation, or apoplexy and is not necessarily related to intrinsic tumor biology.

Objective: To systematically review the literature and describe the clinical characteristics and treatment strategies of patients with pituitary carcinomas.

Alterations in the RB Pathway With Inactivation of RB1 Characterize Glioblastomas With a Primitive Neuronal Component.

A primitive neuronal component is a feature of some glioblastomas but defining molecular alterations of this histologic variant remains uncertain. We performed next-generation sequencing of 1500 tumor related genes on tissue from 9 patients with glioblastoma with a primitive component (G/PN) and analyzed 27 similar cases from the Cancer Genome Atlas (TCGA) dataset. Alterations in the RB pathway were identified in all of our patients' tumors and 81% of TCGA tumors with the retinoblastoma tumor suppressor gene (RB1) commonly affected.

The efficacy of immunohistochemistry in the diagnosis of molecular genetic alterations in central nervous system gliomas: Next-generation sequencing of 212 mutations in 112 patients.

Identification of molecular genetic alterations has become an important part of diagnosis and care of patients with brain tumors. Comparisons of immunohistochemistry (IHC) with DNA sequencing techniques have suggested that IHC is useful for identifying surrogates of mutations in gliomas; however, studies of the efficacy are relatively few. Our aim was to compare IHC in our neuropathology laboratory with a commercially available next-generation sequencing (NGS) platform, Tempus xT.

Extraneural metastatic anaplastic ependymoma: a systematic review and a report of metastases to bilateral parotid glands.

Background: Anaplastic ependymoma with extraneural metastases is associated with a poor clinical outcome. Metastatic spread to the parotid gland is a rare clinical entity that requires multidisciplinary intervention. Herein, we present a systematic review of anaplastic ependymoma with extraneural metastases and report on a case with metastases to both parotid glands.

Glycine by MR spectroscopy is an imaging biomarker of glioma aggressiveness.

Background: High-grade gliomas likely remodel the metabolic machinery to meet the increased demands for amino acids and nucleotides during rapid cell proliferation. Glycine, a non-essential amino acid and intermediate of nucleotide biosynthesis, may increase with proliferation. Non-invasive measurement of glycine by magnetic resonance spectroscopy (MRS) was evaluated as an imaging biomarker for assessment of tumor aggressiveness.

Mutation Status and Epithelial Differentiation Stratify Recurrence Risk in Chordoid Meningioma-A Multicenter Study with High Prognostic Relevance.

Chordoid meningioma is a rare WHO grade II histologic variant. Its molecular alterations or their impact on patient risk stratification have not been fully explored. We performed a multicenter, clinical, histological, and genomic analysis of chordoid meningiomas from 30 patients (34 tumors), representing the largest integrated study to date.

Distinct Expression Patterns of Carbonic Anhydrase IX in Clear Cell, Microcystic, and Angiomatous Meningiomas.

Clear cell, microcytic, and angiomatous meningiomas are 3 vasculature-rich variants with overlapping morphological features but different prognostic and treatment implications. Distinction between them is not always straightforward. We compared the expression patterns of the hypoxia marker carbonic anhydrase IX (CA-IX) in meningiomas with predominant clear cell (n = 15), microcystic (n = 9), or angiomatous (n = 11) morphologies, as well as 117 cases of other World Health Organization recognized histological meningioma variants.

Intracranial anaplastic hemangiopericytoma presenting with simultaneous extra-cranial metastases: A case report and review of the literature.

Background: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare mesenchymal tumor with a propensity to recur and metastasize extracranially years after treatment. Accordingly, there are no reported cases of a patient presenting with a simultaneous intracranial primary and extracranial metastases. We present the case of a patient presenting with an intracranial SFT/HPC and simultaneous liver metastases and propose a treatment paradigm.

Stem cell injections for axial back pain: a systematic review of associated risks and complications with a case illustration of diffuse hyperplastic gliosis resulting in cauda equina syndrome.

Objective: Axial low-back pain is a disease of epidemic proportions that exerts a heavy global toll on the active workforce and results in more than half a trillion dollars in annual costs. Stem cell injections are being increasingly advertised as a restorative solution for various degenerative diseases and are becoming more affordable and attainable by the public. There have been multiple reports in the media of these injections being easily available abroad outside of clinical trials, but scientific evidence supporting them remains scarce.

Genome-Wide Analysis of Glioblastoma Patients with Unexpectedly Long Survival.

Glioblastoma (GBM), representing WHO grade IV astrocytoma, is a relatively common primary brain tumor in adults with an exceptionally dismal prognosis. With an incidence rate of over 10 000 cases in the United States annually, the median survival rate ranges from 10-15 months in IDH1/2-wildtype tumors and 24-31 months in IDH1/2-mutant tumors, with further variation depending on factors such as age, MGMT methylation status, and treatment regimen. We present a cohort of 4 patients, aged 37-60 at initial diagnosis, with IDH1-mutant GBMs that were associated with unusually long survival intervals after the initial diagnosis, currently ranging from 90 to 154 months (all still alive).

Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis.

Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing.

H3 K27M Mutations in Thalamic Pilocytic Astrocytomas with Anaplasia.

Background: The revised World Health Organization classification of central nervous system tumors, published in 2016, has recognized the H3 K27M mutation as a critical genetic signature defining a new group of infiltrative astrocytomas designated as diffuse midline glioma, H3 K27M mutant. Although most H3 K27M mutations arise in the setting of diffusely infiltrative tumors, there are rare reports of compact tumors with low-grade histologic features harboring this mutation. The prevalence and clinical significance of this mutation in pilocytic astrocytomas remain unclear.

Successful Novel Treatment of a Paraspinal Primitive Neuroectodermal Tumor with Predominantly Glial Differentiation: A 3-Year Follow-Up After Surgery, Intensity-Modulated Radiation Therapy and Oral Temozolomide.

Background: Paraspinal masses are a relatively uncommon but diverse group of lesions that can be neoplastic or non-neoplastic. Peripheral primitive neuroectodermal tumors of the lumbar paraspinal region with diffuse and strong glial differentiation have never been reported before.

Case Description: We report a primary paraspinal primitive neuroectodermal tumor with overwhelming glial differentiation in a 23-year-old female patient who presented with intractable right lower extremity pain.

BRAF mutation leading to central nervous system rosai-dorfman disease.

Rosai-Dorfman disease (RDD) is an uncommon histiocytic proliferative disorder that can present in nodal, extranodal, or, extremely rarely, in central nervous system (CNS)-restricted form. RDD is characterized histologically as a non-Langerhans cell histiocytosis composed of atypical CD68 /S-100 /CD1a macrophages demonstrating prominent emperipolesis and effacement of the surrounding tissue. Previously thought to represent a reactive process, recent studies have raised the possibility that RDD and other histiocytic lesions, including Erdheim-Chester and Langerhans cell histiocytosis, are clonal processes linked to somatic mutations in the mitogen-activated protein (MAP) kinase pathway.

Epithelial differentiation with microlumen formation in meningioma: diagnostic utility of NHERF1/EBP50 immunohistochemistry.

Meningioma is a primary brain tumor arising from the neoplastic transformation of meningothelial cells. Several histological variants of meningioma have been described. Here we show that NHERF1/EBP50, an adaptor protein required for structuring specialized polarized epithelia, can distinguish meningioma variants with epithelial differentiation.

Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration.

Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator in response to hypoxia and its transcriptional activity is crucial for cancer cell mobility. Here we present evidence for a novel epigenetic mechanism that regulates HIF-1 transcriptional activity and HIF-1-dependent migration of glioblastoma cells. The lysine methyltransferases G9a and GLP directly bound to the α subunit of HIF-1 (HIF-1α) and catalyzed mono- and di-methylation of HIF-1α at lysine (K) 674 in vitro and in vivo.

Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis.

Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults.