LETTER TO THE EDITOR Heterogeneous Pattern of Differentiation With BCAS1/NABC1 Expression in a Case of Oligodendroglioma Mar  ıa Jos e Ulloa-Navas, MSc 1 , Luis Rubio, PhD 2 , Anna Teruel-Sanchis, MSc 1 , Jorge Pe~ na-Pe~ na, BSc 1 , Jos e Manuel Garc  ıa-Verdugo, PhD 1 , Vicente Herranz-P erez, PhD 1,3 , and Jaime Ferrer-Lozano, MD Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, Universitat de Va- le `ncia, CIBERNED, Valencia, Spain Department of Pathology, Hospital Universitari i Polite `cnic La Fe, Valencia, Spain Predepartamental Unit of Medicine, Faculty of Health Sciences, Universitat Jaume I, Castell o de la Plana, Spain Correspondence to: Vicente Herranz-P erez, Institute Cavanilles of Biodiversity and Evolutionary Biology, Laboratory of Com- parative Neurobiology, C/ Catedr atico Jos e Beltr an Mart  ınez, 2, 46980 Paterna, Valencia, Spain; E-mail: vicente.herran- z@uv.es To the Editor: Oligodendrogliomas (ODGs) have been defined as IDH-mutant, 1p/19q-codeleted diffuse gliomas by the 2016 WHO Classification of Tumours of the Central Nervous Sys- tem (1–3). The histogenesis underlying gliomas is still elu- sive, and the cell of origin for gliomas has not been clearly defined. However, glial progenitors have been suggested as possible candidates for malignant glioma generation (4). Moreover, NG2-glia and PDGFRa-expressing oligodendro- cyte progenitors (OPCs) have been identified in some astro- cytomas and ODGs as a direct evidence of tumorigenesis originating from these cell types (5, 6). More recent research based on genetic evidence indicates that ODGs may not have a unique cell of origin, but that they can arise from ventricular-subventricular zone-like stem cells, oligodendro- cyte or astrocyte progenitor cells (7). The study of ODG cellular heterogeneity may offer fur- ther insight into the complexity of tumor constituents and how they might influence the malignant behavior. To better under- stand this aspect, state-of-the-art multi-omics studies (8, 9) have subclassified 1p/19q-codeleted diffuse gliomas into dif- ferent inter and intratumoral populations, according to the ge- nomic features they display, or the common markers that tumor cells share with immature ventricular-subventricular zone cells (i.e. oligodendrocytes, OPCs, neuronal precursors, or stem cells). These analyses show that in anaplastic ODGs there is a subpopulation of cells that express OPC markers and exhibit more aggressive behavior due to MYC upregulation (8). Therefore, to improve our current understanding of the histogenesis and diversity of ODG biology, new markers of differentiation should be studied. Herein, we describe a re- markable case of an ODG presenting diverse histologic fea- tures and phenotypic heterogeneity labeled with the novel marker BCAS1/NABC1 (brain enriched myelin associated protein 1, encoded by BCAS1 gene located on 20q13.2). BCAS1 expression has been recently proposed as a marker that defines a discrete maturation stage of oligodendrocytes in the human brain (10). BCAS1-positive cells or premyeli- nating oligodendrocytes have been studied in the white matter of nonpathologic brains and in the brain of multiple sclerosis patients, but not as a marker of a specific population within an ODG. Therefore, to our knowledge, this is the first report of discrete, clustered BCAS1-positive nodules in a glioma. A casual finding was made in a neurologically asymp- tomatic 65-year-old woman, who underwent MRI examina- tion prior to oral surgery. Clinical history revealed a thalamic stroke. The patient presented a T2-hyperintense, noncontrast- enhancing mass in her right frontal lobe, measuring 55 mm in greatest dimension, surrounded by edema. A complete en bloc surgical resection was performed. The patient has been free of disease for 2 years following adjuvant chemoradiotherapy. Histopathologic analysis disclosed a heterogeneous pic- ture (Fig. 1A), with a main component of classical ODG, growing diffusely in sheets of tightly packed uniform tumor cells with scant cytoplasm, round nuclei, and perinuclear clear halos. The tumor harbored very few mitotic figures. Rounded microcalcifications were seen within the tumor sheets. These cells diffusely invaded the adjacent cortex, showing perineuronal and perivascular satellitosis. On the other hand, small, relatively well-defined nodules were seen in the superficial white matter. These nodules were in direct transition with the diffuse, sheet-like cortical tumor growth. They displayed a loosely cohesive tumor cell population, em- bedded in a microvacuolated background. These cells showed more abundant and vacuolated cytoplasm, and moderately pleomorphic nuclei with irregular contour and rare mitoses. Together with the previous patterns, tumor cells invaded the subcortical white matter forming rows or ill-defined columns, as well as vague rosettes. Immunohistochemical assessment showed expression of mutant IDH1 (R132H) protein in all tumor areas (Fig. 1B), 379 V C 2020 American Association of Neuropathologists, Inc. All rights reserved. J Neuropathol Exp Neurol Vol. 80, No. 4, April 2021, pp. 379–383 doi: 10.1093/jnen/nlaa144 Downloaded from https://academic.oup.com/jnen/article/80/4/379/6129327 by guest on 29 September 2022