CNS 肿瘤伴 BCOR 内部串联重复（BCOR ITD）CNS tumor with BCOR internal tandem duplication

Definition / general

• Malignant neoplasm of the central nervous system (CNS)
• Internal tandem duplication (ITD) involving exon 15 of the BCOR gene

Essential features

• Malignant neoplasm of the CNS
• Predominantly solid growth of uniform appearing, solid to spindled tumor cells in a dense capillary network with pseudorosette formation
• BCOR ITD involving exon 15
• For unresolved lesions, DNA methylation profile of CNS tumor with BCOR ITD

Terminology

• Not recommended
  • CNS high grade neuroepithelial tumor with BCOR internal tandem duplication
  • CNS primitive neuroepithelial tumor (CNS PNET)

ICD coding

• ICD-O: 9500/3 - CNS tumor with BCOR internal tandem duplication
• ICD-11: 2A00.1Y - other specified embryonal tumors of brain

Epidemiology

• Primarily affects children (median age of 3.2 years); no sex predilection (Brain Pathol 2020;30:46, J Pathol Transl Med 2025;59:273)
• No specific environmental or genetic risk factors (J Pathol Transl Med 2025;59:273)

Sites

• Most commonly in the cerebral or cerebellar hemispheres; rarely involves the basal ganglia, brainstem or spinal cord (Cell 2016;164:1060, Brain Pathol 2020;30:46)

Pathophysiology

• BCOR (chromosome Xq26.2) is an epigenetic and transcriptional regulator (Genes Dev 2000;14:1810, Nat Cell Biol 2009;11:1002)
• Somatic heterozygous BCOR ITD, likely producing a gain of function (activating) mutation, plays an important role in tumorigenesis but cellular mechanisms remain unclear (Cell 2016;164:1060)
• WNT signaling activation is frequently observed, which may contribute to tumorigenesis (Cell 2016;164:1060)

Clinical features

• Symptoms and clinical presentation are based on tumor location and are usually related to increased intracranial pressure (e.g., headache, nausea, vomiting)
• Some patients present with focal neurologic deficits or seizures
• Reference: Brain Pathol 2020;30:46

Diagnosis

• Brain imaging, preferably MRI
• Histopathologic and molecular analyses of surgically resected tissue to arrive at final diagnosis

Radiology description

• By MRI: large, well defined, intra-axial masses, often abutting the dura, with areas of necrosis, calcification or hemorrhage (AJNR Am J Neuroradiol 2022;43:151)
  • T1 hypointense with heterogeneous enhancement
  • T2 / FLAIR hyperintense
  • Diffusion weighted imaging / apparent diffusion coefficient (DWI / ADC): reduced diffusivity

Radiology images

Contributed by Jared T. Ahrendsen, M.D., Ph.D.; Nitin Wadhwani, M.D. Additional MRI feature images hosted on other servers were not archived locally.

Prognostic factors

• Prognosis is generally poor, with many patients experiencing disease recurrence and a 5 year overall survival rate of ~50% (Brain Pathol 2020;30:46)
• One study reported a median survival of 1.7 years among 46 published cases (Pathol Res Pract 2022;236:153995)
• Rare cases of long term survival (> 10 years) have been reported (Brain Pathol 2020;30:46)

Case reports

• 18 month old boy with torticollis and vomiting (Childs Nerv Syst 2023;39:321)
• 5 year old boy with a left frontal tumor (NMC Case Rep J 2023;10:343)
• 6 year old girl and 3 year old boy with CNS tumors with BCOR ITD (Pathol Res Pract 2022;236:153995)

Treatment

• Maximal safe surgical resection followed by chemotherapy and often radiation therapy (Brain Pathol 2020;30:46)

Frozen section description

• Smear preparation: round to oval tumor cells with open chromatin, eosinophilic cytoplasm and often with delicate fibrillary cellular processes
• Frozen: compact growth, well demarcated from adjacent brain, with perivascular pseudorosettes; necrosis is common (Cytopathology 2024;35:561)

Intraoperative frozen / smear cytology images

Microscopic (histologic) description

• Well demarcated from adjacent brain with solid growth, though focal areas of infiltration can occur
• Uniform appearing, spindled to oval cells with fine chromatin
• Abundant branching capillary network
• Necrosis is common with variable mitotic activity
• Glioma-like fibrillarity and perivascular pseudorosettes are common; tumor cells occasionally form rosette-like structures
• Other features that are variably encountered: myxoid / microcystic changes, microcalcifications, hyalinized stroma and dense cellularity with brisk mitotic activity
• References: Brain Pathol 2020;30:46, Brain Pathol 2018;28:710, Acta Neuropathol Commun 2020;8:105

Microscopic (histologic) images

Cytology description

• Round to oval tumor cells with open chromatin, eosinophilic cytoplasm and often with delicate fibrillary cellular processes (Cytopathology 2024;35:561)

Cytology images

No separate images were provided in this section of the original topic.

Positive stains

• Uniformly positive for vimentin, CD56 and BCOR
• Most tumors are variably positive for Olig2 and NeuN
• Ki67: 15 - 60%
• Reference: Brain Pathol 2020;30:46

Negative stains

• GFAP and synaptophysin are predominantly negative
• EMA is either negative or faint granular cytoplasmic staining
• Reference: Brain Pathol 2020;30:46

Electron microscopy description

• Not used for routine diagnosis
• Primitive cells with abundant rough endoplasmic reticulum (Brain Pathol 2020;30:46)

Electron microscopy images

Ultrastructural feature images from the original topic were hosted on other servers and were not archived locally.

Molecular / cytogenetics description

• Defined by the presence of heterozygous ITD in exon 15 of BCOR (Cell 2016;164:1060)
  • This is the same alteration seen in clear cell sarcoma of kidney and primitive myxoid mesenchymal tumor of infancy (Nat Genet 2015;47:861, Am J Surg Pathol 2016;40:1009)
• Additional genetic alterations are uncommon but there are rare cases with co-occurring TP53, ATRX or CDKN2A / CDKN2B alterations (Brain Pathol 2020;30:46)
• Demonstrates a DNA methylation profile that aligns with CNS tumor with BCOR ITD (Nature 2018;555:469)

Sample pathology report

• Brain, left frontal tumor, resection:
  • CNS tumor with BCOR internal tandem duplication, CNS WHO grade 4 (see comment)
  • Comment: Histology reveals an embryonal neoplasm with solid growth, uniform oval nuclei and branching capillary network. Necrosis and elevated mitotic activity are observed and there are occasional perivascular pseudorosettes. The tumor cells are variably positive for Olig2 and negative for GFAP and synaptophysin. Molecular studies reveal an internal tandem duplication involving exon 15 of the BCOR gene and DNA methylation profiling matched with high confidence to methylation class CNS tumor with BCOR ITD.

Differential diagnosis

Ependymoma

• Located along / near ventricle
• IHC positive for GFAP (diffuse) and EMA (perinuclear dot-like)
• IHC predominantly negative for Olig2
• Distinct molecular pathology, including gene fusions for supratentorial tumors and epigenetic signature for posterior fossa tumors (posterior fossa ependymoma group A / group B)

Atypical teratoid / rhabdoid tumor (AT / RT)

• Malignant embryonal neoplasm generally encountered in infancy
• Poorly differentiated tumor cells with variably present rhabdoid morphology
• Loss of INI1 expression by immunohistochemistry
• Biallelic inactivation of SMARCB1 or (rarely) SMARCA4

Medulloblastoma

• Occur in the cerebellum / fourth ventricle
• Prototypical small round blue cell tumor of the CNS
• Tumor cells are positive for synaptophysin and (variably) GFAP

Embryonal tumor with multilayered rosettes (ETMR)

• Multilayered rosettes of malignant embryonal cells
• Strong, diffuse cytoplasmic reactivity for LIN28
• C19MC genetic alteration or (rarely) DICER1 mutation

Pediatric type high grade glioma

• Diffusely infiltrative growth pattern
• Usually positive for both GFAP and Olig2
• Hemispheric tumors in children may harbor H3 G34 alteration
• DNA methylation profile aligns with diffuse pediatric type high grade glioma or other high grade glioma classes

• References: Am J Surg Pathol 2017;41:1254, Brain Pathol 2020;30:46, Acta Neuropathol Commun 2020;8:105

Additional references

No entries listed in this section of the original topic.

Practice question #1

A 4 year old child presented with a large brain mass located in the superficial right frontal lobe. The tumor was resected and histology findings are shown in the image above. Molecular testing reveals an internal tandem duplication (ITD) of exon 15 in the BCOR gene. What is the most likely immunophenotype of this tumor?

1. GFAP negative, Olig2 negative, NeuN negative
2. GFAP negative, Olig2 positive, NeuN positive
3. GFAP positive, Olig2 negative, NeuN positive
4. GFAP positive, Olig2 positive, NeuN negative
5. GFAP positive, Olig2 positive, NeuN positive

Practice answer #1

B. GFAP negative, Olig2 positive, NeuN positive. The clinical vignette describes a CNS tumor with BCOR ITD. The typical immunophenotype for this tumor is positive expression for Olig2 and NeuN and negative expression for GFAP and synaptophysin. Answers A, C, D and E are incorrect because they are not the immunophenotype for CNS tumor with BCOR ITD.

Practice question #2

A 3 year old child presented with a large brain mass located in the cerebellum. The mass was resected and histopathologic evaluation reveals a malignant neoplasm with compact growth pattern, uniform appearing oval cells with occasional pseudorosettes in a capillary rich background and areas of necrosis. By immunohistochemistry, the tumor cells are variably positive for Olig2 and positive for NeuN, ATRX and INI1; the tumor cells are negative for GFAP, synaptophysin, IDH1 R132H and H3 K27M. Which molecular alteration is most likely present in this tumor?

1. BCOR exon 15 internal tandem duplication (ITD)
2. Biallelic loss of SMARCB1
3. EGFR gene amplification
4. H3 G34R mutation
5. KIAA1549::BRAF fusion

Practice answer #2

A.BCOR exon 15 internal tandem duplication (ITD). The vignette describes classic histology and immunophenotype of CNS tumor with BCOR ITD. The malignant CNS tumor is defined by the presence of ITD of exon 15 in the BCOR gene. Answer B is incorrect because biallelic loss of SMARCB1 is characteristic of atypical teratoid / rhabdoid tumor; however, the tumor here has retained INI1. Answers C and D are incorrect because EGFR gene amplification and H3 G34R mutation are more commonly observed in high grade gliomas, such as glioblastoma or diffuse hemispheric glioma, respectively. Answer E is incorrect because KIAA1549::BRAF gene fusion is characteristic of pilocytic astrocytoma (especially those in the cerebellum), which is a low grade glial neoplasm.

Cite this page: Ahrendsen JT. CNS tumor with BCOR internal tandem duplication. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorbcor.html. Accessed September 15th, 2026.

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