Academic literature on the topic 'Multiple Multifocal Glioma High-Grade'

A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, sleep apnea, alcohol use disorder in remission, renal cell carcinoma, and mucinous adenocarcinoma of the lung sought care for evaluation of presumed limbic encephalitis. Six months before evaluation, he had development of anxiety, fatigue, and blurry vision. He was diagnosed with renal cell carcinoma, which was resected. Subsequently, worsening depression developed, which required self-admitted psychiatric hospitalization for suicidal ideation. After discharge he had subacute development of aphasia, inability to recognize family members, and delusions for which he was hospitalized. Brain magnetic resonance imaging demonstrated a large, partly expansile, T2/fluid-attenuated inversion recovery–hyperintense lesion involving the left hippocampus and parahippocampal gyrus, as well as temporal neocortex and white matter, which was interpreted as limbic encephalitis. Spinal fluid analysis showed 66 total nucleated cells/μ‎L with 93% lymphocytes, normal cytologic findings, protein concentration of 66 mg/dL, and 15 erythrocytes/μ‎L. The Kokmen short test of mental status indicated mainly an amnestic profile without delirium, with a total score of 31 of 38. Given the patient’s neuroimaging findings for limbic encephalitis and lack of clear encephalopathy, the initial focus was confirming or ruling out the diagnosis of limbic encephalitis. He underwent repeated cerebrospinal fluid analysis, which showed 3 total nucleated cells/μ‎L with a protein concentration of 67 mg/dL. Serum autoantibody testing showed a low-titer glutamic acid decarboxylase 65-kDa isoform antibody value of 0.17 nmol/L. Brain magnetic resonance imaging 3 months after his initial magnetic resonance imaging showed slight progression of the expansile, left temporal lobe, T2-hyperintense lesion, further involving the left parietal lobe white matter, temporal lobe neocortex, and splenium of the corpus callosum, without clear gadolinium enhancement. A diagnosis of anaplastic astrocytoma (World Health Organization grade III) was made. He was treated with temozolomide and radiotherapy, with radiographic improvement. However, he had development of medically refractory focal seizures with secondary generalization. Approximately 3 years after his initial diagnosis, the patient experienced functional decline, with brain magnetic resonance imaging demonstrating multiple new, bihemispheric, T2-hyperintense lesions concerning for multifocal glioma. Given his poor prognosis and functional status, the patient was transitioned to comfort care. The presentation of disease in this patient highlights the importance of neuroimaging interpretation in the context of clinical history. Although this case patient had some features that could suggest a paraneoplastic limbic encephalitis—including behavioral changes, seizure, systemic malignancy, and apparent clinical response to immunosuppression—several features were inconsistent with this diagnosis.

High-grade glioma (HGG) such as glioblastoma multiforme (GBM) is an aggressive brain tumor that is still associated with poor prognosis. With the discovery and advancement in understanding of cancer stem cells (CSC) in glioma, these cells have emerged as seed cells for tumor growth and recurrence and appear as a potential target for therapeutics. Glioma stem cells (GSCs) demonstrate capacity of self-renewal, proliferation, and differentiation into multiple cell types and can contribute to tumor heterogeneity. Their role is established in tumorigenesis, metastasis, chemo- and radio-resistance and appears as a major cause for tumor recurrence. Thus, targeting GSCs by various therapeutics may improve effectiveness of the drugs in use alone or in combination to significantly improve patient survival outcome in GBM cases. In this chapter, we have discussed various mechanisms that drive GSC including signaling pathways and tumor microenvironment. We have also discussed the mechanism behind resistance of GSCs toward therapeutics and the pathways that can be targeted to improve the outcome of the patients.

A 48-year-old woman sought care for progressive right arm and hand pain with radial nerve–distribution sensory loss. She had a past history of multiple prior athletics-associated, musculoskeletal, upper cervical spine injuries. Her symptoms were initially attributed to a right C6 radiculopathy. Over the next several months, the sensory loss spread to involve the entire right hand and subsequently the entire left hand. She had development of diffuse right hand weakness and a sense of imbalance that was particularly prominent while in the dark. Finally, she experienced progressive constipation and urinary retention. Magnetic resonance imaging of the cervical spine showed an expanded cervical spinal cord from C3 through C7-T1 with diffuse T2-hyperintense changes and heterogeneous gadolinium enhancement most prominent at C5-6. In combination with a congenitally small central canal, severe central canal narrowing was seen at C5-6 and moderate narrowing at C4-5. Magnetic resonance imaging of the brain and thoracic spine were normal, and magnetic resonance imaging of the lumbar spine indicated only mild lumbar spondylosis. On suspicion of a spinal cord neoplasm with a secondary compressive myelopathy, C3 through C7 laminectomy and posterior instrumented fusion from C2 through T1 was performed, with a biopsy obtained at the C5-6 level. Postoperatively, her gait and right upper extremity pain improved. The biopsy showed atypical glial cells. Neurofilament staining demonstrated an infiltrative pattern. Atypical cells were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, and a Lys27Met sequence variation of histone H3, with overexpression of p53 on immunohistochemical staining. There was loss of H3 K27-trimethylation on the infiltrating cells, corresponding to the presence of Lys27Met sequence variation of histone H3. These findings were diagnostic for diffuse midline glioma with Lys27Met sequence variation of histone H3 (World Health Organization grade IV). A total of 5,400 cGy of photon radiation was delivered in 30 fractions over 42 days. She was subsequently treated with an oral histone deacetylase inhibitor, panobinostat, for 12 months. During this time, she had clinical response to treatment and reported improvement in balance and numbness. Follow-up magnetic resonance imaging at 3 months showed a slight decrease in the size of the mass, and this response was sustained 1 year post radiotherapy. Diffuse midline gliomas that contain Lys27Met sequence variation of histone H3are incurable, often inoperable, midline brain tumors that are most commonly seen in the pediatric population. These tumors can also occur in adult patients and are considered high grade, even in the absence of features such as necrosis or microvascular proliferation.