CNS tumor
Ependymal tumors
RELA fusion positive ependymoma


Topic Completed: 19 September 2019

Revised: 19 September 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: RELA fusion positive ependymoma

Janice Seulgy Ahn, M.D.
Shih-Hsiu
Page views in 2019 to date: 988
Cite this page: Ahn JS, Wang SH. RELA fusion positive ependymoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumorependymomarelafusion.html. Accessed December 10th, 2019.
Definition / general
  • Supratentorial ependymomas without specific histopathologic features, defined by presence of a RELA fusion gene
  • 1 of 3 molecular subtypes of supratentorial ependymomas (Cancer Cell 2015;27:728)
  • WHO grades II - III, depending on histology
Essential features
  • Most common supratentorial ependymoma subtype in children (Nature 2014;506:451)
  • Detection of RELA fusion gene with FISH is diagnostic
  • Poor prognosis
ICD coding
Epidemiology
Sites
Pathophysiology
Diagnosis
  • MRI, biopsy
Radiology description
  • Well circumscribed supratentorial masses (most in lateral or third ventricles but may not have obvious connection to a ventricle) with various degrees of contrast enhancement on gadolinium enhanced MRI
  • Intratumoral hemorrhage, calcification or cystic components may be present
Radiology images

Images hosted on other servers:

Diffusion restriction and 
hyperdensity

T1, T2, FLAIR and DWI

Cystic mass with seeding and metastasis

Prognostic factors
Case reports
Treatment
  • Surgical resection is the mainstay (Neuro Oncol 2016;18:902)
  • Postoperative radiation is a possible effective adjuvant therapy for grade III ependymomas or low grade tumors not amenable to complete resection (Neuro Oncol 2016;18:902)
Gross description
  • Well circumscribed, tan, spongy, occasionally with gritty calcium deposits
Microscopic (histologic) description
  • Monomorphic cells with ovoid nuclei and speckled nuclear chromatin
  • Perivascular pseudorosettes and ependymal true rosettes
  • May have prominent branching capillaries or clear cell change
  • Uncommon variants of ependymoma, such as tanycytic ependymoma, are less likely to harbor RELA fusion
Microscopic (histologic) images

Images hosted on other servers:

Sheets of monomorphic
cells and microvascular
proliferation, L1CAM+

Metastatic RELA fused ependymoma to the liver

Pseudorosettes,
mitoses, necrosis 
and
microvasculature,
L1CAM+

Perivascular pseudorosettes

Monomorphic cells
with perivascular
pseudorosettes,
L1CAM+

Positive stains
Negative stains
Molecular / cytogenetics description
  • Interphase FISH with break apart probes flanking RELA gene reveals split signals; also detected by PCR
  • Associated with homozygous CDKN2A deletions (Cancer Cell 2015;27:728)
Sample pathology report
  • Brain, left frontal tumor, resection:
    • Ependymoma, RELA fusion positive (see comment)
    • Comment: The neoplasm is characterized by perivascular pseudorosettes, prominent branching capillaries and clear cell change. The neoplastic cells are positive for GFAP, EMA and L1CAM. RELA fusion is detected by FISH with break apart probes (see separate cytogenetics report for details). These findings support the diagnosis of a RELA fusion positive ependymoma, a recently described molecular subgroup of supratentorial ependymomas associated with poor prognosis.
Differential diagnosis
  • Supratentorial
    • Ependymoma lacking RELA fusion gene
      • Balanced genome supratentorial ependymoma (good prognosis)
        • Papillary: finger-like projections lined by ependyma
        • Clear cell: prominent perinuclear haloes (RELA fused ependymomas can have focal clear cell change)
        • Tanycytic: ependymal cells arranged in elongated fascicles
      • YAP1 fusion positive supratentorial ependymomas (good prognosis): YAP1+
  • Infratentorial compartment / posterior fossa
    • Posterior fossa ependymoma type A (poor prognosis): location in the posterior fossa, absence of C11orf95-RELA fusion, diffuse loss of H3K27me3 by immunohistochemistry (Acta Neuropathol 2017;134:705)
    • Posterior fossa ependymoma type B (good prognosis): location in the posterior fossa, absence of C11orf95-RELA fusion, intact H3K27me3 by immunohistochemistry (Acta Neuropathol 2017;134:705)
  • Spinal cord
    • Myxopapillary ependymoma (good prognosis): location in the posterior fossa, particularly in the conus medullaris, cauda equina and filum terminale region; grossly gelatinous, histologically demonstrating cells with elongated, fibrillary processes arranged around vessels in an Alcian blue+ myxoid cystic background
  • Other reportedly L1CAM+ central nervous system tumors
Board review question #1
Shown in the linked image is an L1CAM immunostain in an ependymoma. Which of the following is true about this entity?



  1. The histologic features correspond to anaplastic ependymoma, WHO grade III
  2. The immunohistochemical stain is confirmed by FISH
  3. This immunophenotype is characteristic of posterior fossa ependymomas
  4. This immunophenotype may also be seen in central neurocytoma, anaplastic astrocytoma and primitive neuronal tumors
Board review answer #1
B. The immunohistochemical stain is confirmed by FISH

Reference: RELA fusion positive ependymoma

Comment Here
Board review question #2
Which of the following combinations of ependymoma molecular subtype and clinical characteristics is correct?

  1. Posterior fossa ependymoma, subtype A / supratentorial / poor
  2. Spinal myxopapillary ependymoma / supratentorial / good
  3. Supratentorial ependymoma, RELA / children / poor
  4. Supratentorial ependymoma, YAP1 / adults / good
Board review answer #2
C. Supratentorial ependymoma, RELA / children / poor

Reference: RELA fusion positive ependymoma

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