Abstract
BACKGROUNDGangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, particularly serine–threonine protein kinase B-RAF alterations. Fusions involving neurotrophin tyrosine receptor kinase (NTRK) genes have rarely been reported in ganglioglioma. Similarly, echinoderm microtubule-associated protein-like (EML) 4 gene fusion has been described in lung cancer, but none has been reported in ganglioglioma.OBSERVATIONSThis report discusses the care of a 72-year-old man presenting with medication-refractory, left-sided focal seizures who was found to have a nongadolinium-enhancing, T2-hyperintense, right frontoparietal lesion. The patient received resection, and histological analysis found a World Health Organization grade I ganglioglioma, with genetic analysis demonstrating an EML4-NTRK3 gene fusion protein.LESSONSTo our knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3, in an adult ganglioglioma, which is otherwise mostly associated with BRAF alterations and activation of the mitogen-activated protein kinase signaling pathway. Further studies are needed to elucidate the function of the resultant fusion protein and determine whether it may serve as a future therapeutic target.
Highlights
Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, serine–threonine protein kinase B-RAF alterations
The TRK Family neurotrophin tyrosine receptor kinase (NTRK) genes (NTRK 1, 2, and 3) encode tropomyosin receptor kinase (TRK) proteins, including TRKA, TRKB, and TRKC proteins, which are membrane-bound proteins that dimerize, phosphorylate, and activate downstream signaling cascades via phospholipase C-gamma (PLC-g), phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein (MAP) kinase, and protein kinase C pathways when bound with neurotrophins; this leads to activation of downstream effectors responsible for neuronal survival and differentiation.[10,11]
TRK activation in cancer has been identified to occur via mutations, splice variants, TRK overexpression, and, most commonly, NTRK fusions.[11]
Summary
Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, serine–threonine protein kinase B-RAF alterations. Gangliogliomas have been described in the literature as early as 19471 and are classically described as well-differentiated, slow-growing glioneuronal neoplasms composed of dysplastic ganglion cells and neoplastic glial cells They are the most common epilepsy-associated neoplasm and account for 2% of all primary tumors.[2] they are typically histologically low grade, anaplastic transformation of the glial component can rarely occur.[3] They can present at any age, most are diagnosed in children and young adults before 30 years of age, with a slight male preponderance.[4] They vary radiographically, histologically, and geographically within the central nervous system (CNS), including supratentorial, infratentorial, and spinal intramedullary lesions. To the authors’ knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3, in an adult ganglioglioma, further expanding the known genetic profile of these CNS tumors
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