Molecular characteristics of incidental lower-grade glioma for treatment decision-making.

OBJECTIVE: Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the "wait-and-see" strategy or immediate treatment. Therefore, in this study the authors explored iLGG's clinical and molecular landscape to improve its management. METHODS: The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed. RESULTS: There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation-related, cell migration-related, epithelial-to-mesenchymal transition-related, and negative regulation of cell death-related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide. CONCLUSIONS: The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.

Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NLRC4 Inflammasome.

Tim-3/Gal-9 and the NLRC4 inflammasome contribute to glioma progression. However, the underlying mechanisms involved are unclear. Here, we observed that Tim-3/Gal-9 expression increased with glioma malignancy and found that Tim-3/Gal-9 regulate NLRC4 inflammasome formation and activation. Tim-3/Gal-9 and NLRC4 inflammasome-related molecule expression levels increased with WHO glioma grade, and this association was correlated with low survival. We investigated NLRC4 inflammasome formation by genetically regulating Tim-3 and its ligand Gal-9. Tim-3/Gal-9 regulation was positively correlated with the NLRC4 inflammasome, NLRC4, and caspase-1 expression. Tim-3/Gal-9 did not trigger IL-1ß secretion but were strongly positively correlated with caspase-1 activity as they induced programmed cell death in glioma cells. A protein-protein interaction analysis revealed that the FYN-JAK1-ZNF384 pathways are bridges in NLRC4 inflammasome regulation by Tim-3/Gal-9. The present study showed that Tim-3/Gal-9 are associated with poor prognosis in glioma patients and induce NLRC4 inflammasome formation and activation. We proposed that a Tim-3/Gal-9 blockade could be beneficial in glioma therapy as it would reduce the inflammatory microenvironment by downregulating the NLRC4 inflammasome.

Novalis Stereotactic Radiosurgery for Spinal Dural Arteriovenous Fistula.

The spinal dural arteriovenous fistula (SDAVF) is rare, presenting with progressive, insidious symptoms, and inducing spinal cord ischemia and myelopathy, resulting in severe neurological deficits. If physicians have accurate and enough information about vascular anatomy and hemodynamics, they achieve the good results though the surgery or endovascular embolization. However, when selective spinal angiography is unsuccessful due to neurological deficits, surgery and endovascular embolization might be failed because of inadequate information. We describe a patient with a history of vasospasm during spinal angiography, who was successfully treated by spinal stereotactic radiosurgery using Novalis system.

Pleomorphic Adenoma with Sarcomatous Change in a Lacrimal Gland.

A 69-year-old man was referred with left exophthalmos. Computed tomographic (CT) findings detected a well-circumscribed mass in the left side of the intraorbital cavity. At that time, he refused the further evaluation and treatment. About three years later, the size of the mass had enlarged, and the patient's symptoms were getting worse. The mass was completely removed with frontotemporal craniotomy and superolateral orbitotomy. In operative findings, the mass had originated in the lacrimal gland and was well-encapsulated without invasion to the surrounding tissue. In the pathologic findings, the tumor consisted of pleomorphic adenoma with osteosarcomatous change of stromal components. Postoperatively, the adjuvant radiotherapy was done four weeks later. The patient's symptoms were improved. The pleomorphic adenoma with osteosarcomatous change is extremely rare and appropriate treatment is not clearly established. We would like to report this rare case with a review of the literature.

Neurocutaneous melanosis in association with dandy-walker complex with extensive intracerebral and spinal cord involvement.

Neurocutaneous melanosis (NCM) is a rare congenital syndrome consisting of benign or malignant melanotic tumors of the central nervous system with large or numerous cutaneous melanocytic nevi. The Dandy-Walker complex (DWC) is characterized by an enlarged posterior fossa with high insertion of the tentorium, hypoplasia or aplasia of the cerebellar vermis, and cystic dilatation of the fourth ventricle. These each two conditions are rare, but NCM associated with DWC is even more rare. Most patients of NCM with DWC present neurological symptoms early in life such as intracranial hemorrhage, hydrocephalus, and malignant transformation of the melanocytes. We report a 14-year-old male patient who was finally diagnosed as NCM in association with DWC with extensive intracerebral and spinal cord involvement.