Temporal lobe myxoid glioneuronal tumor, PDGFRA p.K385L‐mutant with DNA methylation confirmation

Myxoid glioneuronal tumor (MGNT) is a newly recognized tumor type in the fifth edition of the WHO Classification of CNS tumors (CNS WHO 2021) (1). Histologically similar to dysembryoplastic neuroepithelial tumor (DNT) or, less commonly, to rosette-forming glioneuronal tumor, MGNT is currently defined by the presence of specific mutation in the platelet-derived growth factor receptor α (PDGFRA) gene, namely, p.K385 mutation (changing K385 from a basic amino acid to a hydrophobic amino acid, usually L or I). MGNT was initially described in the septum pellucidum, septal nuclei, corpus callosum and lateral ventricle/ periventricular white matter (2–4), but has recently been reported in the midbrain tectum by our group (5). We now add to the literature a second example of a non-septum pellucidum location for this tumor in the temporal lobe, with both the mutation and confirmation by DNA methylation testing. This 10-year-old female was managed for seizures for 9 months before presenting to our pediatric specialty hospital. Magnetic resonance imaging demonstrated a nonenhancing T2-hyperintense lesion in the anterior right temporal lobe measuring up to 2.0 2.7 1.5 cm (Figures 1A and S1). The tumor was cortically based, extending anteriorly to the periphery of the anterior mesial temporal cortex and superiorly into the amygdala. The tumor extended superficially into the periventricular white matter with thin septations pointing toward the ventricle but showed no intraventricular extension and did not involve the septum verum. The tumor manifested no surrounding edema or mass effect. Radiologic features were considered classic for DNT, although the multicystic/ bubbly appearance that is often seen in DNT was not present. The lesion was stable on serial imaging over the next several months. However, seizure frequency and intensity increased despite antiepileptic drug treatment, prompting the decision to resect the tumor. A right temporal lobectomy was performed. Histologic examination showed a mucin-rich tumor containing columns of uniform small round oligodendroglia-like cells with delicate chromatin (Figure 1B,C). Scant floating neurons were present (Figure 1C, inset), with typical larger nuclei, prominent nucleoli, and modest cytoplasm; neuronal origin of the floating neurons was confirmed on NeuN immunohistochemical stain (Millipore) (Figure 1D). Mitotic activity was absent and MIB1 was less than 1%. Although diagnostic consideration was given to several low-grade epilepsy associated tumors, CD34 immunohistochemical stain (Ventana) was negative, Rosenthal fibers or eosinophilic granular bodies were absent, and dysmorphic neurons/ ganglion cells were not present, ruling out polymorphous low-grade neuroepithelial tumor of the young (PLNTY), pilocytic astrocytoma or ganglioglioma, respectively. Given the histology, tumor location and the radiologic findings, the initial histologic diagnosis was DNT. Location within the temporal lobe allowed assessment for possible focal cortical dysplasia in the adjacent cortex of this seizure-producing lesion. The associated cortical resection specimen showed abnormal cortical architecture with disruption of tangential neuronal lamination on hematoxylin and eosin (Figure 1E), with better appreciation on NeuN immunostain (Figure 1F). There were no radial architectural abnormality, dysmorphic neurons, or balloon cells. Next-generation sequencing (NGS) mutation panel demonstrated a dinucleotide PDGFRA somatic mutation, resulting in PDGFRA p.K385L alteration. The tumor was negative for clinically significant mutations or gene fusions reported in diffuse gliomas, including IDH1/2, histone genes H3F3A, H3F3B, HIST1H1C, HIST1H3B, or HIST1H3C. NGS was further negative for alterations in BRAF, FGFR1, 2, 3, NF1, PIK3CA, and PIK3R1, genetic alterations often found in low-grade glial or glioneuronal tumors such as pilocytic astrocytoma, ganglioglioma, PLNTY or DNT; the complete list of genes covered in our 300+ gene fusion and mutation panels have been reported in our previous publication (5). PDGFRA p.K385L alteration was the sole genetic alteration identified and is likely to result in an oncogenic, gain-of-function mutation that causes constitutive activation of the kinase domain in the absence of ligand (4,6). Global DNA methylation has been shown to reduce interobserver variability and improve diagnostic precision in CNS tumor diagnosis (7,8). We, therefore, performed DNA methylation profiling using standard methods, described in detail in our prior publication (5). The output . idat files were uploaded to the German Cancer Research Center (DKFZ) web interface (https://www.molecularneuropathology. org/ Received: 13 January 2022 Accepted: 25 April 2022