CNS & pituitary tumors

Other tumors

Cauda equina neuroendocrine tumor


Editorial Board Member: P.J. Cimino, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Eman Abdelzaher, M.D., Ph.D.

Last author update: 2 May 2024
Last staff update: 2 May 2024

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

PubMed Search: Paraganglioma CNS

Eman Abdelzaher, M.D., Ph.D.
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Cite this page: Abdelzaher E. Cauda equina neuroendocrine tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorparaganglioma.html. Accessed May 19th, 2024.
Definition / general
  • Low grade, well circumscribed neuroendocrine neoplasm of cauda equina / filum terminale region
  • CNS WHO grade 1
  • Distinct from paragangliomas and pheochromocytomas outside the central nervous system (CNS) (Acta Neuropathol 2020;140:907)
Essential features
  • Grade 1, slow growing neuroendocrine neoplasm of cauda equina / filum terminale region
  • Rare entity with a benign clinical course (J Neurooncol 2015;122:539)
  • Generally affects adults
  • Distinct from paragangliomas and pheochromocytomas outside the CNS (Acta Neuropathol 2020;140:907)
Terminology
ICD coding
  • ICD-O: 8693/3 - cauda equina neuroendocrine tumor (previously paraganglioma)
  • ICD-11
    • 2A02.0Y & XH1X68 - other specified gliomas of spinal cord, cranial nerves or other parts of the central nervous system & paraganglioma, benign
    • 2A02.0Y & XH0EW6 - other specified gliomas of spinal cord, cranial nerves or other parts of the central nervous system & paraganglioma, NOS
Epidemiology
Sites
Pathophysiology
  • Histogenetically, biologically and molecularly distinct from paragangliomas and pheochromocytomas outside the CNS (Acta Neuropathol 2020;140:907)
  • Arises from specialized neural crest cells in the cauda equina / filum terminale region
  • mRNA analyses revealed that cauda equina paragangliomas overexpress the transcription factor HOXB13 (which is developmentally expressed in the caudal extent of the spinal cord) as opposed to pheochromocytomas / paragangliomas of other regions of the body; this provides circumstantial evidence of their cellular origin (Neuropathol Appl Neurobiol 2021;47:889)
  • Molecular alterations that drive tumorigenesis in cauda equina neuroendocrine tumors are unknown
Etiology
Clinical features
Diagnosis
  • Rarely a clinical or radiological diagnosis
  • Neuroimaging: magnetic resonance imaging (MRI) (modality of choice) and computed tomography (CT) (Neurosurg Rev 2022;45:103)
  • Biopsy
  • WHO essential and desirable diagnostic criteria
    • Essential
      • Well demarcated tumor with zellballen architecture
      • Synaptophysin or chromogranin immunoreactivity in chief cells
      • Cauda equina location
      • Methylation profile of cauda equina neuroendocrine tumor (for unresolved lesions)
    • Desirable
      • S100 positive sustentacular cells
      • Cytokeratin positive chief cells
      • Reticulin silver stain showing typical architecture
Laboratory
Radiology description
  • MRI
    • Well circumscribed, intradural extramedullary, sausage shaped mass at cauda equina / filum terminale region (Radiol Case Rep 2019;14:1185)
    • Solid, occasionally partly cystic
    • Generally T1 hypointense to isointense and T2 isointense to hyperintense, with intense post contrast enhancement (Neurosurg Rev 2022;45:103)
    • Although MRI findings are nonspecific and indistinguishable from other solid tumors in cauda equina region, certain characteristic MRI findings could suggest the diagnosis, including a salt and pepper appearance on T2 weighted images related to the hypervascular nature (42.1%), a peripheral hypointense rim (cap sign) on T2 weighted images caused by subcapsular hemosiderin (47.3%) and serpiginous flow voids on all sequences (78.9%) (J Neurooncol 2015;122:539)
    • Perfusion weighted MR images show increased blood flow, consistent with hypervascular tumor (Radiol Case Rep 2019;14:1185)
    • Polar sign may be seen in T1 contrast enhanced and T2 weighted MR images, representing subacute to chronic polar intratumoral hematomas (J Spine Neurosurg 2014;3:4)
  • Spinal angiography reveals a well defined hypervascular lesion with intense early blush that persists well into the arterial and venous phases (silk cocoon appearance), which helps presurgical planning and differentiates CEPs from other spinal tumors (Radiol Case Rep 2019;14:1185, Neurosurg Focus 2015;39:E16)
  • CT: may show scalloping of the vertebral bodies (J Surg Tech Case Rep 2012;4:46)
Radiology images

Images hosted on other servers:
Cauda equina paraganglioma

MRI

Intradural enhancing lesion

Intradural enhancing lesion

Spinal angiography

Spinal angiography

Scalloping of lumbar vertebrae

Scalloping of lumbar vertebrae

Prognostic factors
Case reports
Treatment
Clinical images

Images hosted on other servers:
Cauda equina paragangliomas

Intraoperative

Lesion after durotomy

Lesion after durotomy

Hypervascular well marginated mass

Hypervascular well marginated mass

Gross description
  • Well circumscribed, delicately encapsulated, oval to sausage shaped vascular mass
  • Smooth surfaced, soft, red-brown and bleeds freely (Histopathology 1997;31:167)
  • Size ranges from 10 mm to 112 mm in greatest dimension
  • May show capsular calcification or cystic change
  • Gross appearance resembles myxopapillary ependymoma
  • If submitted with attached filum terminale, proximal and distal ends should be sampled as surgical margins
Gross images

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Lesion after en block removal

Lesion after en block removal

Hemorrhagic cystic change

Hemorrhagic cystic change

Frozen section description
Frozen section images

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Intraoperative frozen section

Ependymoma-like features

Microscopic (histologic) description
  • Well differentiated, encapsulated and richly vascular tumor
  • Organoid (zellballen) architecture: nests or lobules of chief (type I) cells surrounded by sustentacular (type II) cells with intervening delicate capillary and reticulin networks (J Neurooncol 2015;122:539)
  • Chief cells
    • Uniform round or polygonal epithelioid cells
    • Round to oval nuclei with salt and pepper chromatin pattern and inconspicuous nucleoli (J Surg Tech Case Rep 2012;4:46)
    • Finely granular eosinophilic cytoplasm, may be amphophilic or clear (Acta Neuropathol 2020;140:907)
    • Sharp cell borders, particularly around vessels
    • No or mild degenerative nuclear pleomorphism (endocrine atypia), of no prognostic significance
  • Sustentacular cells
    • Spindle shaped cells with attenuated long processes
    • Perilobular; surround chief cell lobules
    • Inconspicuous by routine light microscopy (visible by IHC for S100)
  • Mitotic activity is highly variable (0 - 5/10 high power fields), of no prognostic significance (Acta Neuropathol 2020;140:893)
  • Other common features
  • Less common features
Microscopic (histologic) images

Contributed by Eman Abdelzaher, M.D., Ph.D.
Encapsulated lesion Encapsulated lesion

Encapsulated lesion

Zellballen architecture Zellballen architecture

Zellballen architecture

Zellballen architecture

Zellballen architecture

Salt and pepper chromatin

Salt and pepper chromatin


Focal sclerosis

Focal sclerosis

Reticulin

Reticulin

Synaptophysin Synaptophysin

Synaptophysin

S100 positive sustentacular cells

S100 positive sustentacular cells

S100 positive chief and sustentacular cells

S100 positive chief and sustentacular cells


GFAP negative

GFAP negative

GFAP positive sustentacular cells

GFAP positive sustentacular cells

EMA

EMA

Low Ki67

Low Ki67

Cytology description
Positive stains
Negative stains
Electron microscopy description
  • Chief cells
  • Sustentacular cells
    • Electron dense with elongated processes
    • Contain some intermediate filaments
    • Lack neurosecretory granules
Electron microscopy images

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Numerous perinuclear dense core granules

Numerous perinuclear dense core granules

Prominent, rough endoplasmic reticulum

Prominent rough endoplasmic reticulum and Golgi apparatus

Molecular / cytogenetics description
  • Distinct DNA methylation and chromosomal copy number profiles as opposed to those of paragangliomas arising from other locations (Acta Neuropathol 2020;140:907)
  • DNA methylation profiling and clustering analysis showed that CEPs are epigenetically distinct from extraspinal paragangliomas, pheochromocytomas, other neuroendocrine tumors and glial or ependymal neoplasms of the spinal cord (Acta Neuropathol 2020;140:907)
  • Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3 and 11, none of which were present in the cohort of CEP (Acta Neuropathol 2020;140:907)
  • RNA and DNA exome sequencing revealed that SDH mutations are absent in cauda equina paragangliomas (Acta Neuropathol 2020;140:893)
  • CEPs are not driven by recurrent oncogenic gene fusions; fusion genes known to be relevant in paragangliomas / pheochromocytomas and associated with poor prognosis (e.g., MAML3 fusions) were not observed in CEPs (Acta Neuropathol 2020;140:893)
Molecular / cytogenetics images

Images hosted on other servers:
DNA methylation cluster analysis of CEPs and other tumors

DNA methylation cluster analysis of CEPs and other tumors

Chromosomal copy number analysis

Chromosomal copy number analysis

Videos

Case 8: paraganglioma of the filum terminale

Sample pathology report
  • Cauda equina mass, total resection:
    • Cauda equina neuroendocrine tumor (cauda equina paraganglioma), CNS WHO grade 1 (see comment)
    • Comment: Encapsulated tumor with zellballen architecture highlighted by reticulin histochemical stain. The tumor is composed of chief cells (synaptophysin positive) arranged in nests surrounded by S100 positive sustentacular cells.
    • Molecular genetics: methylation profile of cauda equina neuroendocrine tumor
Differential diagnosis
Board review style question #1

A 49 year old man presented with lower back pain and sciatica for a duration of 3 months. MRI showed cauda equina intradural extramedullary enhancing vascular mass. The received gross specimen was a delicately encapsulated oval mass with a red-brown cut section. The images shown above depict the histological features of the lesion and synaptophysin immunostain. What is the most likely diagnosis?

  1. Cauda equina paraganglioma
  2. Hemangioblastoma
  3. Myxopapillary ependymoma
  4. Schwannoma
Board review style answer #1
A. Cauda equina paraganglioma. The location of the tumor at the cauda equina region together with the histologically distinctive zellballen architecture and synaptophysin positive chief cells are diagnostic of cauda equina paraganglioma. Answer B is incorrect because hemangioblastomas have vacuolated stromal cells and are synaptophysin negative. Answer C is incorrect because myxopapillary ependymomas show characteristic perivascular myxoid change and are synaptophysin negative. Answer D is incorrect because schwannomas do not have a zellballen architecture and are synaptophysin negative.

Comment Here

Reference: Cauda equina neuroendocrine tumor
Board review style question #2
Which of the following statements about cauda equina paraganglioma is correct?

  1. Encapsulated tumors with zellballen architecture and synaptophysin immunoreactivity
  2. It is commonly functioning with clinical features of catecholamine hypersecretion
  3. It shares common genetic profile with extraspinal paragangliomas and pheochromocytomas
  4. Recurrence rate after total resection is high
Board review style answer #2
A. Encapsulated tumors with zellballen architecture and synaptophysin immunoreactivity. Zellballen architecture and synaptophysin positive chief cells are characteristic of cauda equina paraganglioma. Answer B is incorrect because functional activity is extremely rare in cauda equina paraganglioma. Answer D is incorrect because recurrence rate after total resection is low (around 7%). Answer C is incorrect because cauda equina paragangliomas are molecularly distinct from paragangliomas and pheochromocytomas outside the CNS.

Comment Here

Reference: Cauda equina neuroendocrine tumor
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