CNS & pituitary tumors

Embryonal tumors

Other embryonal tumors

CNS neuroblastoma, FOXR2 activated


Editorial Board Member: P.J. Cimino, M.D., Ph.D.
Deputy Editors-in-Chief: Debra L. Zynger, M.D., Chunyu Cai, M.D., Ph.D.
Sarah A. Anderson, D.O.
Nirupama Singh, M.D., Ph.D.

Last author update: 28 September 2023
Last staff update: 13 October 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: CNS neuroblastoma, FOXR2 activated

Sarah A. Anderson, D.O.
Nirupama Singh, M.D., Ph.D.
Page views in 2024 to date: 1,810
Cite this page: Anderson SA, Singh N. CNS neuroblastoma, FOXR2 activated. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnsneuroblastoma.html. Accessed July 13th, 2024.
Definition / general
  • CNS neuroblastoma, FOXR2 activated (CNS NB FOXR2) tumors are embryonal neoplasms characterized by poorly differentiated neuroblastic or neuronal differentiation with variable neuropil rich stroma and ganglion cells
  • Characterized by the activation of FOXR2 by structural rearrangements
Essential features
  • Embryonal tumor with neuronal or neuroblastic differentiation and activation of FOXR2 rearrangement and fusion or a DNA methylation profile aligned with CNS neuroblastoma, FOXR2 activated
Terminology
  • CNS neuroblastoma, FOXR2 activated
  • Formerly recognized as one of the primitive neuroectodermal tumors of CNS (CNS PNETs)
ICD coding
  • ICD-O: 9500/3 - neuroblastoma, NOS
  • ICD-10: C71 - malignant neoplasm of brain
  • ICD-11: 2A00.1Y & XH85Z0 - other specified embryonal tumors of brain & neuroblastoma, NOS
Epidemiology
Sites
  • Supratentorial
Pathophysiology
  • Thought to arise from neuroectodermal cells, although the exact cell of origin is not known (J Neuropathol Exp Neurol 2021;80:52)
  • Most frequent genetic alterations are on the transcription factor gene FOXR2 (Cell 2016;164:1060)
  • Although FOXR2 plays a causative role in the formation of CNS embryonal tumors, the exact underlying mechanisms have yet to be determined (Neuro Oncol 2019;21:993)
Etiology
  • Risk factors have not been reported
Clinical features
Diagnosis
  • Embryonal tumor with neuronal or neuroblastic differentiation and activation of FOXR2 rearrangement and fusion or a DNA methylation profile aligned with CNS neuroblastoma, FOXR2 activated
Laboratory
  • No specific laboratory findings for this entity
Radiology description
Radiology images

Images hosted on other servers:
T2 weighted and postcontrast T1 weighted axial

T2 weighted and postcontrast T1 weighted axial

Prognostic factors
  • Favorable survival for patients with CNS NB FOXR2; higher rate of recurrences in nonirradiated and locally irradiated patients (Neuro Oncol 2021;23:1597)
Case reports
Treatment
Gross description
  • CNS embryonal tumors are often pink, soft, well circumscribed masses; if a prominent desmoplastic component is present, it is often tan-white and firm
Microscopic (histologic) description
  • Poorly differentiated neuroepithelial cells and neurocytic cells (Cell 2016;164:1060)
    • Uniform small cells with high N:C ratio, oval to round with hyperchromatic nuclei
    • Cells have little to no apparent cytoplasm in a background of neuropil with or without Homer Wright rosettes (J Neuropathol Exp Neurol 2021;80:52)
  • Background of neuropil rich stroma
  • Abundant mitotic activity
  • Palisading necrosis can be present
  • Infiltration of adjacent parenchyma is variable
Microscopic (histologic) images

Contributed by Nirupama Singh, M.D., Ph.D., Carmen Perrino, M.D. and P.J. Cimino, M.D., Ph.D.
Neuroblasts with no cytoplasm

Neuroblasts with no cytoplasm

Homer Wright rosettes

Homer Wright rosettes

Small tumor cells

Small tumor cells

High power pseudorosettes

Pseudorosettes


Embryonal cells

Embryonal cells

Neurocytic cells

Neurocytic cells

Focal ganglion cells

Focal ganglion cells

Necrosis

Necrosis

MVP

MVP

Cytology description
  • Evaluation of cerebrospinal fluid (CSF) for the presence of tumor cells is required for staging (Radiology 1969;93:1351)
Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
  • Interchromosomal and intrachromosomal rearrangements in forkhead box R2, leading to increased FOXR2 gene expression
    • FOXR2 locus on chromosome Xp11.21
    • Common fusion partner is JMJD1C locus on chromosome 10q21.3
  • Gain of chromosome 1q is present in most cases (Neuro Oncol 2021;23:1597)
  • High FOXR2 expression can occur in a subset of high grade gliomas and medulloblastomas; however, DNA methylation profiling can distinguish these entities (Cell 2016;164:1060)
Molecular / cytogenetics images

Images hosted on other servers:
Recurrent molecular alterations

Recurrent molecular alterations

Videos

Case presentation of CNS NB FOXR2

Sample pathology report
  • Brain, suprasellar mass, resection:
    • CNS neuroblastoma, FOXR2 activated, CNS WHO grade 4 (see comment)
    • Comment: Sections of the suprasellar tumor demonstrate small, round, embryonic appearing cells with scant cytoplasm. Necrosis and abundant mitotic activity are appreciated. Immunohistochemical stains for synaptophysin and Ki67 were performed. Synaptophysin is patchy positive. Ki67 proliferation index is ~25%.
    • Molecular pathology findings
      • FOXR2 fusion
      • Gain of chromosome 1q
Differential diagnosis
Board review style question #1
A 2 year old boy presents with seizures. MRI reveals a well circumscribed supratentorial mass with a mixed solid and cystic appearance. Which of the following is the most likely diagnosis?

  1. Ewing sarcoma
  2. Lymphoma
  3. Neuroblastoma
  4. Testicular germ cell tumor
Board review style answer #1
C. Neuroblastoma. In this age group, neuroblastoma is the most common of these tumors. Answers A, B and D are incorrect because these diagnoses are less likely in this age group.

Comment Here

Reference: Neuroblastoma
Board review style question #2

This supratentorial mass is composed of small, round, embryonic appearing cells and Homer Wright rosettes. Whole genome analysis demonstrated a FOXR2 fusion. What is the most likely diagnosis?

  1. CNS neuroblastoma, FOXR2 activated
  2. Embryonal tumors with multilayered rosettes
  3. Ependymoma
  4. Medulloblastoma
Board review style answer #2
A. CNS neuroblastoma, FOXR2 activated. This histology along with the molecular findings are consistent with a CNS neuroblastoma, FOXR2 activated. Answers B, C and D are incorrect because although they might be similar morphologically, they will not have a FOXR2 fusion.

Comment Here

Reference: Neuroblastoma
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