Chenoweth David, Syed Hashim, Teferi Nahom, Challa Meron, Persons Jane E, Eschbacher Kathryn L, Seblani Maggie, Dlouhy Brian J
1Department of Neurosurgery, University of Iowa Hospital and Clinics, Iowa City, Iowa.
2Carver College of Medicine, University of Iowa, Iowa City, Iowa.
J Neurosurg Case Lessons. 2024 Mar 4;7(10). doi: 10.3171/CASE23638.
Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group.
A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as "glioneuronal tumor kinase-fused" (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib.
This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.
神经胶质神经元肿瘤（GNTs）是一类罕见的中枢神经系统（CNS）肿瘤，具有不同程度的神经元和神经胶质分化，主要影响儿童和年轻人。在2021年世界卫生组织（WHO）当前的CNS肿瘤分类中，GNTs包括14种不同的肿瘤类型。最近，全基因组DNA甲基化谱分析的应用使该肿瘤组的分类更加精确。
一名3岁男性，有3个月头围增大、发育里程碑倒退和语言发育迟缓的病史。脑部磁共振成像显示左大脑半球有一个大的多房性肿块，有明显的占位效应和中线移位，接受了近全切除治疗。组织学和分子评估显示为一种含有MYO5A::NTRK3融合的神经胶质神经元肿瘤。通过DNA甲基化谱分析，该肿瘤与一种称为“神经胶质神经元肿瘤激酶融合”（GNT激酶融合）的临时甲基化类别相匹配。该患者后来开始接受拉罗替尼的靶向治疗。
这是小儿GNT中MYO5A::NTRK3融合的首次报告。GNT激酶融合是一种临时甲基化类别，目前未包括在WHO的CNS肿瘤分类中。该病例突出了CNS肿瘤全面分子特征分析的影响，特别是随着新型基因靶向治疗的可用性不断增加。
