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.

Keywords: BCOR ITD; clear cell sarcoma of the kidney; high-grade neuroepithelial tumor.

Figure 1

Radiological images of central nervous system high‐grade neuroepithelial tumors with BCOR alteration (CNS HGNET‐BCOR); A–C: case 2, D–F: case 3. The tumors presented as similar well‐demarcated masses located in the cerebellar or cerebral hemispheres, hypo‐intense on T1‐weighted images (A, D), hyper‐intense on T2‐weighted images (B, E), hyper‐intense on diffusion‐weighted images (F) and with slight to moderate contrast enhancement (C). Partial cystic changes and intratumoral hemorrhage were also observed (D–F).

Figure 2

Microscopic appearance of CNS HGNET‐BCOR. A. A compact growth of tumor cells with delicate branching vessels exhibiting a chicken‐wire appearance (case 3). B. A solid growth of spindle‐shaped cells in bundles (case 5). C. Microcystic formation in a myxoid and edematous background (case 1). D, E. Ependymoma‐like perivascular pseudorosettes in cases 2 and 3, respectively. E. A perivascular anuclear zone formed by the cell processes. F. A sharp interface between the tumor and normal brain parenchyma (case 1). G. Minimal infiltration of isolated tumor cells into the surrounding brain parenchyma (case 2). H, I. High magnification of tumor cells. H. Tumor cells with monotonous round to oval nuclei containing fine chromatin and indistinct to small nucleoli (case 3). I. Mild nuclear size variation and some cells with slightly prominent nucleoli (case 6). J. Tumor cells with small, round nuclei and clear cytoplasm resembling oligodendroglioma cells and neurocytes (case 3). K. Palisading necrosis (case 2). L. A recurrent tumor from subcutaneous seeding (case 2). Original magnification: A, C, F, K, ×100; B, D, G, L, ×200; E, J, ×400; H, I, ×600.

Figure 3

Immunohistochemistry of CNS HGNET‐BCOR. A. Diffuse and strong positivity for vimentin (case 1). B. Patchy positivity for GFAP in the cytoplasm and fibrillary processes of tumor cells (case 1). C. Patchy positivity for S‐100 protein in the cytoplasm and fibrillary processes of tumor cells (case 1). D. Diffuse nuclear immunoreactivity for Olig2 with a mixture of varying degrees of intensity (case 3). E. Scattered immunoreactivity for synaptophysin (case 1). F. Diffuse immunopositivity for neurofilament protein (case 1). G. Diffuse nuclear BCOR staining (case 3). H. BCOR expression highlighted isolated tumor cells infiltrating into the surrounding brain parenchyma (same area as Fig 2G; case 2). Nuclear BCOR immunopositivity was observed in the external granular layer cells in the cerebellum, but was absent in the internal granular layer cells I. Original magnification: A–C, E–I, ×200; D, I inset, ×400.

Figure 4

Histological and immunohistochemical findings of clear cell sarcomas of the kidney (CCSK) and undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI) (A, C, E: CCSK, B, D, F: URCS/PMMTI). A. The classic pattern of CCSK composed of round, oval and polygonal cells, and arborizing capillary vasculature. B. URCS/PMMTI case composed of stellate tumor cells with microcystic formation in a myxoid background. C, D. Diffuse nuclear immunoreactivity for BCOR. E. Focal immunopositivity for neurofilament protein in CCSK. F. Diffuse immunopositivity for neurofilament protein in URCS/PMMTI. Original magnification: A–F, ×200.

Figure 5

BCOR exon 15 aberrations in BCOR ITD‐positive tumors. A. An example of the duplicated coding sequence of CNS HGNET‐BCOR in case 3. The 2‐bp insertion and 88‐bp tandem duplication are illustrated. The nucleotide position is relative to the sequence used as the reference (NM_001123385.1). B. Predicted protein sequences of duplicated regions and genetic changes in the CNS HGNET, CCSK and URCS/PMMTI. At the top, the wild‐type BCOR amino acid sequence from positions 1695 to 1755 is presented (NP_001116857).