CNS high‐grade neuroepithelial tumor with BCOR internal tandem duplication: a comparison with its counterparts in the kidney and soft tissue

Abstract

Central nervous system high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3' end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features. In this study, we performed a clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S-100 protein and synaptophysin were observed in CNS HGNET-BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive tumors, only CNS HGNET-BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS.

Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information

“…BCOR alterations have been recognized in a growing number of tumor subtypes affecting the soft tissue, the kidney or the central nervous system [22,38,39]. Recent studies comparing the molecular and histologic phenotype in these BCOR altered tumors found overlapping features, especially between soft tissue and kidney tumors [38,40,41]. At the level of DNA-methylation, we observed a great overlap in tumors from soft tissue and the kidney carrying BCOR alteration.…”

High‐grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication—a comprehensive clinical, radiographic, pathologic, and genomic analysis

“…Only a few additional patients with HGNET BCOR ex15 ITD have been reported since the initial description of this tumor entity by Sturm et al . As such, the full spectrum of histologic features, accompanying genetic alterations, clinical outcomes, and optimal treatment for this new tumor entity remain largely undefined.…”

Expanding the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas in adults

“…14,15 ZC3H7B-BCOR and BCOR ITD define unique subsets of high-grade endometrial stromal sarcoma (ESS) mostly in adults. [16][17][18] BCOR ITD characterizes a subset of high-grade neuroepithelial tumors, mostly in children, [19][20][21] and EP300-BCOR defines a subset of pediatric glioma. 22 These various types of tumors show similar histology to the musculoskeletal counterpart, although each tumor type has distinct clinical features and/or a unique immunoprofile.…”