A rare MYBL1-altered pediatric-type diffuse astrocytoma with positive OLIG2 and MAP2 expression and high proliferative activity

To the Editor: Pediatric-type low-grade gliomas (pLGGs) were introduced in the fifth edition of the 2021 WHO Classification of Tumors of the CNS tumors.1 These tumors are classified into 4 types, that is, diffuse astrocytoma, MYB- or MYBL1-altered, angiocentric glioma, polymorphous low-grade neuroepithelial tumor of the young, and diffuse low-grade glioma, MAPK pathway-altered.1 Based on the current WHO CNS tumor classification, MYB- and MYBL1-altered diffuse astrocytoma is considered a grade 1 tumor. A recent single-center pediatric study showed a 10-year OS and PFS of 90% and 95%, respectively, suggesting that these lesions are indolent.2 MYB and MYBL1 are thought to act as transcriptional regulators critical for proliferation and differentiation.3,4 Nevertheless, no evidence to date has suggested that this indolent tumor demonstrates substantial proliferative activity. Here, we found a rare pediatric-type diffuse astrocytoma with MYBL1 alterations and unique characteristics. A 17-month-old female toddler presented with a 5-day history of unsteady gait. Cranial MRI showed a mass located in the left cerebellar hemisphere and the cerebellar vermis, measuring 47 × 44 × 46 mm. The mass was hypointense on T1-weighted imaging (Figure 1A) and hyperintense on T2-weighted imaging (Figure 1B) and on FLAIR sequence imaging (Figure 1C), with an indistinct margin. No significant enhancement was observed on the contrast-enhanced image (Figure 1D). Hematoxylin and eosin (H&E) staining revealed relatively monomorphic glial cell proliferation. While most tumor cells had a bland appearance, a subset of cells showed significant atypia (Figure 1E). Immunohistochemical staining of tumor cells was negative for IDH1 R132H and positive for GFAP (Figure 1F and G). In contrast to the typical features of classic diffuse astrocytoma MYB- or MYBL1-altered, OLIG2 and the neuronal marker MAP2 were expressed (Figure 1H and I). The Ki-67 index was up to 20% in some areas, indicating marked proliferative activity (Figure 1J).