CNS tumor
Ependymal tumors
RELA fusion positive ependymoma
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 19 September 2019
Minor changes: 27 June 2020
Copyright: 2019-2020, PathologyOutlines.com, Inc.
PubMed Search: RELA fusion positive ependymoma
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2Cite this page: Ahn JS, Wang SH. RELA fusion positive ependymoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorependymomarelafusion.html. Accessed August 14th, 2020.
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
Epidemiology
- 70% of pediatric supratentorial ependymomas (Nature 2014;506:451)
- Median age of 8 years (range: 0 - 69 years), with 23% in adults (Cancer Cell 2015;27:728)
- M > F (1.6:1) (Cancer Cell 2015;27:728)
Sites
- Brain, supratentorial
- Has not been described in infratentorial compartments (Cancer Cell 2015;27:728)
Pathophysiology
- C11orf95-RELA fusion is most common and is likely the principal driver of this subgroup (Cancer Cell 2015;27:728)
- Fusion secondary to chromothripsis of chromosome 11 (Nature 2014;506:451, Cancer Cell 2015;27:728)
- Fusion leads to constitutive activation of NF kappa B pathway (Nature 2014;506:451)
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
- Worst prognosis of 3 supratentorial molecular subgroups (Cancer Cell 2015;27:728)
Case reports
- 1 year old boy with left parieto-occipital anaplastic ependymoma (Brain Tumor Pathol 2018;35:41)
- 9 year old girl with parafalcine tumor (Neuropathology 2016;36:490)
- 10 year old boy with left frontoparietal anaplastic ependymoma and extracranial metastasis (J Pathol Transl Med 2017;51:588)
- 19 year old man with left frontal tumor (Surg Neurol Int 2018;9:144)
- 35 year old woman with left frontal tumor and subsequent radiation induced sarcomatous transformation (Brain Tumor Pathol 2015;32:105)
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
- GFAP, EMA (as with other ependymomas)
- L1CAM (CD171) (corresponds to presence of RELA fusion, see differential diagnosis) (Am J Surg Pathol 2019;43:56)
- p65 / RELA double immunostaining (92% positive predictive value, 100% negative predictive value) (Am J Surg Pathol 2019;43:56)
- Nestin (96%) (J Neurooncol 2018;138:29)
Negative stains
- More common types of ependymomas are predominantly negative for NeuN; insufficient evidence for RELA fused ependymomas (Histopathology 2006;48:438)
- YAP1
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+
- Balanced genome supratentorial ependymoma (good prognosis)
- Ependymoma lacking RELA fusion gene
- 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
- Olfactory neuroblastoma: arising from cribriform plate, Homer Wright rosettes, GFAP-
- Primitive neuronal tumors: Homer Wright rosettes, synaptophysin+, EMA-
- Central neurocytoma: GFAP-; synaptophysin, NeuN, neuron specific enolase strong and diffusely positive
- Ganglioglioma: temporal lobe cyst with mural nodule, chronic seizure history, combination of glial and atypical neuronal components (Nagai: Brain Tumor, 1st Edition, 1996)
Additional references
Board review style question #1
Shown in the linked image is an L1CAM immunostain in an ependymoma. Which of the following is true about this entity?
- The histologic features correspond to anaplastic ependymoma, WHO grade III
- The immunohistochemical stain is confirmed by FISH
- This immunophenotype is characteristic of posterior fossa ependymomas
- 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
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Reference: RELA fusion positive ependymoma
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Board review style question #2
Which of the following combinations of ependymoma molecular subtype and clinical characteristics is correct?
- Posterior fossa ependymoma, subtype A / supratentorial / poor
- Spinal myxopapillary ependymoma / supratentorial / good
- Supratentorial ependymoma, RELA / children / poor
- Supratentorial ependymoma, YAP1 / adults / good
Board review answer #2
C. Supratentorial ependymoma, RELA / children / poor
Reference: RELA fusion positive ependymoma
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Reference: RELA fusion positive ependymoma
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