Distinct epigenetic and transcriptional profiles of Epstein-Barr virus (EBV) positive and negative primary CNS lymphomas.

Background: Epstein-Barr virus (EBV)+ and EBV- primary CNS lymphomas (PCNSL) carry distinct mutational landscapes, but their transcriptional and epigenetic profiles have not been integrated and compared. This precludes further insights into pathobiology and molecular differences, relevant for classification and targeted therapy.

Methods: 23 EBV- and 15 EBV+ PCNSL, histologically classified as diffuse large B-cell lymphomas, were subjected to RNA-Sequencing and EPIC methylation arrays.

Factors influencing timely diagnosis in neurolymphomatosis.

Background: Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in neurolymphomatosis and factors delaying diagnosis have not been evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort.

Clinical Presentation, Management, and Outcome in Neurolymphomatosis: A Systematic Review.

Background And Objectives: Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts, and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL.

Favorable Radiographic Response in a Patient With an Oligodendroglioma Treated With Azacitidine and Venetoclax for Acute Myeloid Leukemia.

The standard chemotherapy for treating oligodendrogliomas consists of a combination of procarbazine, lomustine, and vincristine (PCV). The combination of hypomethylating agents like azacitidine and BCL2 inhibitors like venetoclax has not been formally studied in the treatment of glial tumors. The combination of these two drugs is commonly used to treat acute myeloid leukemia (AML), with IDH-mutant disease being a particularly sensitive subtype.

Integrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas.

Immunodeficiency-associated primary CNS lymphoma (PCNSL) represents a distinct clinicopathological entity, which is typically Epstein-Barr virus-positive (EBV) and carries an inferior prognosis. Genetic alterations that characterize EBV-related CNS lymphomagenesis remain unclear precluding molecular classification and targeted therapies. In this study, a comprehensive genetic analysis of 22 EBV PCNSL, therefore, integrated clinical and pathological information with exome and RNA sequencing (RNASeq) data.

Myasthenia Gravis in the Setting of Immune Checkpoint Inhibitor Therapy: Practical Considerations and Opinion-Based Approach to Acute Management.

Use of immune checkpoint inhibitors (ICI) is increasing in patients with oncologic disease. Three classes of checkpoint inhibitors exist: anti-PD1 (nivolumab, pembrolizumab), anti-CTLA4 (ipilimumab), and anti-PDL1 (atezolizumab, avelumab, durvalumab). ICI therapy has been used in multiple malignancies including renal cell cancer, non-small-cell lung cancer, and melanoma.

Treatment Options for Recurrent Primary CNS Lymphoma.

Primary CNS lymphoma (PCNSL) constitutes a rare extranodal variant of non-Hodgkin lymphoma (NHL) with an annual incidence of 0.45/100,000. Given the paucity of large prospective clinical trials, there is no consensus treatment for refractory or relapsed (r/r) PCNSL, and available strategies are largely based on retrospective analyses.

Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors.

Background: Phase 1/2 dose-escalation and expansion study evaluating varlilumab, a fully human agonist anti-CD27 mAb, with nivolumab in anti-PD-1/L1 naïve, refractory solid tumors.

Methods: Phase 1 evaluated the safety of varlilumab (0.1-10 mg/kg) with nivolumab (3 mg/kg) administered once every 2 weeks.

Clinical Reasoning: A 73-Year-Old Woman With Episodic Dysarthria and Horizontal Binocular Diplopia.

A 73-year-old woman presented with transient episodes of dysarthria and horizontal diplopia. She had stereotactic radiosurgery 18 years prior for a retroclival meningioma. Neurologic examination was notable for right-sided tongue deviation, tongue fasciculations, and intermittent impaired abduction of the right eye.

Clinical Reasoning: A 64-Year-Old Man With History of Meningitis Presenting With Proximal Weakness of the Arms.

A 64-year-old man presented for evaluation of proximally pronounced weakness of the arms with preserved facial and lower extremity strength. Symptoms slowly developed over the last 2 years, and the patient's history was notable for severe meningitis 4 years before presentation, which was adequately treated with antibiotics. On examination, symptoms clinically reassembled man-in-the-barrel syndrome and localized to the cervicothoracic central cord.

Hemorrhage Into a Subependymal Giant Cell Astrocytoma in an Adult With Tuberous Sclerosis: Case Report.

Background: We present an uncommon cause of intracranial hemorrhage in a young adult. Tuberous sclerosis complex is a rare genetic disorder characterized by skin changes, benign systemic or central nervous system tumors [subependymal giant cell astrocytoma (SEGA)], mental retardation, or epilepsy. Hemorrhage into SEGA is exceedingly rare.

ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response.

Exome sequencing identifies SLIT2 variants in primary CNS lymphoma.

SLIT2 constitutes a known tumour suppressor gene, which has not yet been implicated in the pathogenesis of primary central nervous system lymphoma (PCNSL). Performing exome sequencing on paired blood and tumour DNA samples from six treatment-naïve PCNSL patients, we identified novel SLIT2 variants (p.N63S, p.

Neurotoxicities associated with immune checkpoint inhibitor therapy.

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as a promising class of cancer immunotherapies. Neurotoxicities are uncommon, but often severe, and potentially fatal complications of ICIs, and clinical experience is limited. The aim of this study is to further define the clinical spectrum and outcome of ICI-mediated neurotoxicities.

Extent and prognostic value of MGMT promotor methylation in glioma WHO grade II.

MGMT promotor methylation is associated with favourable outcome in high-grade glioma. In glioma WHO grade II, it is unclear whether the extent of MGMT promotor methylation and its prognostic role is independent from other molecular markers. We performed a retrospective analysis of 155 patients with glioma WHO grade II.

Autoimmune disease-related primary CNS lymphoma: systematic review and meta-analysis.

Background: Recent studies suggest a relatively high prevalence of autoimmune disorders (AD) among primary CNS lymphoma (PCNSL) patients, however, the literature is limited to case reports. To gain a better understanding of AD-PCNSL we reviewed and analyzed all cases described in the literature.

Methods: We searched the MEDLINE database using the search terms 'central nervous system lymphoma' or 'CNS lymphoma' along with AD-related terms.

Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases.

Purpose: Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare pre-treatment patient characteristics and outcomes between the two treatment options.

Methods: Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018.

Leptomeningeal dissemination of low-grade neuroepithelial CNS tumors in adults: a 15-year experience.

Background: Leptomeningeal dissemination (LD) in adults is an exceedingly rare complication of low-grade neuroepithelial CNS tumors (LGNs). We aimed to determine relative incidence, clinical presentation, and predictors of outcome.

Methods: We searched the quality control database of the Section of Neuro-Oncology, Yale Cancer Center, for patients with LGN (WHO grade I/II) seen between 2002 and 2017.

Primary dural lymphomas: Clinical presentation, management, and outcome.

Background: Clinical experience is limited for primary central nervous system (CNS) lymphoma that arises from the dura mater, which is denoted with the term primary dural lymphoma (PDL). This study was aimed at determining the relative incidence, presentation, and outcomes of PDL.

Methods: The institutional databases of the Divisions of Neuro-Oncology at the Massachusetts General Hospital and the Yale School of Medicine were retrospectively searched for patients with primary CNS lymphoma.

Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report.

Background: Atrial myxomas are generally considered benign neoplasms. The majority of tumors are sporadic and less than 10% are associated with an autosomal dominant condition known as the Carney complex, which is most often caused by germline mutation in the gene PRKAR1A. Whether this gene plays a role in the development of sporadic myxomas has been an area of debate, although recent studies have suggested that some fraction of sporadic tumors also carry mutations in PRKARIA.

Prognostic markers for immunodeficiency-associated primary central nervous system lymphoma.

Background: Immunodeficiency is a major risk factor for primary central nervous system lymphoma (PCNSL), but data on the disease in immunocompromised hosts are scarce. We aimed to define clinical and imaging features and determine prognostic factors for immunodeficiency-associated PCNSL.

Methods: All PCNSL cases seen at Yale-New Haven Hospital between 2002 and 2017 were retrospectively screened for immunodeficiency.

Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells.

Chimeric antigen receptor (CAR) T cells have emerged as a promising class of cell-based immunotherapy in refractory malignancies. Neurotoxicity represents a common and potentially life-threatening adverse effect of CAR T cells, and clinical experience is limited. Here, we describe the clinical presentation and management of 25 adult patients who presented with neurotoxic syndromes after CAR T-cell therapy at the Massachusetts General Hospital.

Paraneoplastic neurological syndromes: a single institution 10-year case series.

Background: Given its rare incidence, there are few epidemiological case series on paraneoplastic neurologic syndromes (PNS).

Methods: We present a 10-year series compiled in the Section of Neuro-Oncology, Yale Cancer Center between 2002 and 2012.

Results: Twenty-five cases met the PNS Euro-network criteria for definitive PNS.