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Ependymoma

Definition

Well circumscribed glial tumor with primarily ependymal features (WHO grade II or III).

Clinical Features

Pathogenesis

  • Female genital tract and mediastinal cases may represent ‘lopsided’ (i.e. monodermal) teratomas
  • Controversy over role of simian virus 40 (SV40)8

Histopathology

  • Dense meshwork of fibrillary cytoplasmic processes:
    • condense, collar-like, about stromal blood vessels
    • formations are known as perivascular pseudorosettes (Fig. 1
      Ependymoma. The cytoplasmic processes of ependymal tumor cells condense about blood vessels to form pseudorosettes.

      Fig. 1: Ependymoma. The cytoplasmic processes of ependymal tumor cells condense about blood vessels to form pseudorosettes.

      )
    • accompanied in minority of cases by canals, tubules or actual rosettes lined by cells closely resembling normal ependymocytes (Fig. 2
      Ependymoma. The true ependymal rosette contains a well-defined central lumen. Clustered ciliary basal bodies (‘blepharoplasts’) are responsible for the enhanced, granular staining of tumor cell apices.

      Fig. 2: Ependymoma. The true ependymal rosette contains a well-defined central lumen. Clustered ciliary basal bodies (‘blepharoplasts’) are responsible for the enhanced, granular staining of tumor cell apices.

      )
  • Tumor cell nuclei:
    • rounded or spindled
    • characteristically evenly granular chromatin distribution
    • generally:
      • lack nucleoli
      • uniform
    • may contain invaginated cytoplasmic pseudoinclusions
    • may exhibit longitudinal nuclear grooving:10
      • optimally visualized in cytologic preparations
      • facilitates intraoperative diagnosis:
        • along with tendency of neoplastic ependymal cells to remain attached to delicate blood vessels in papillary fashion when smeared or crushed
    • occasionally:
      • scattered pleomorphic elements
      • ‘giant cells’:
        • in cranial compartment11
        • in filar region12
  • Commonly dystrophic calcification
  • Sometimes osseous or chondroid metaplasia13
  • Variants:
    • Melanotic14
    • ‘xanthomatous’ containing intracytoplasmic lipid droplets15
    • examples harboring adipocyte-like, ‘lipomatous’ elements16
    • rarely extensive gemistocytic change:
      • one report of globular, inclusion-like cytoplasmic bodies immunoreactive for GFAP17
  • Ultrastructurally:

Special Stains and Immunohistochemistry

Papillary Ependymomas

  • Label for:
    • S-100 protein
    • vimentin
    • GFAP
    • may be apical EMA (a feature potentially shared by ependymal rosettes)
    • may be cytoplasmic AE1/3 anti-keratin ‘cocktail’
  • Usually do not immunolabel for:
    • CAM 5.2
    • CK7
    • CK20
    • CK90321

Diagnosis

Cellular Ependymoma

  • Term for densely populated examples with relatively narrow pseudorosettes but little mitotic activity
  • Conveys no clinically useful information

Tanycytic Ependymomas

  • Greek tangos, to stretch
  • Subset with confounding histologic features:8
  • May be confused with schwannomas, meningiomas, and fibrillary or pilocytic astrocytomas due to:
    • spindly cytologic features
    • fascicular growth patterns
    • poorly developed, inconspicuous pseudorosettes
  • Typically at spinal levels

Clear Cell Ependymomas

  • Practically restricted to supratentorial compartment22
  • Often misconstrued as oligodendroglial
  • Frequently intratumoral calcospherules and plexiform vascular network
  • Retain identifying ependymal attributes ultrastructurally

Papillary Ependymomas

  • Neoplastic ependymal cells:
    • assume columnar configuration
    • are supported by fibrovascular cores rather than fibrillary glial ‘stroma’
  • Very rare
  • Distinguish from:
    • metastatic papillary carcinomas
    • choroid plexus papillomas
    • papillary meningiomas:
  • Differentiated immunohistochemically20,21,23,24

Differential Diagnosis

Medulloblastoma

  • Only exceptionally any appreciable mineralization
  • Usually hangs from fourth ventricular roof when midline

Epithelial Neoplasms of Choroid Plexus

  • May harbor focal ependymocytic populations with GFAP-immunoreactive elongated and tapering cytoplasmic processes (underscores shared neurocytogenesis)
  • Show:
    • more diffuse labeling for CAM 5.2 and CK7
    • transthyretin expression
    • elaboration of continuous basement membranes demonstrable by assessment for laminin25

Papillary Meningiomas

  • Some described as GFAP-immunoreactive, but:
    • extra-axial, dural-based neoplasms
    • do not show ependymal characteristics by electron microscopy

Genetics

  • Alterations of NF-2 tumor suppressor gene on chromosome 22q12 in:8
    • sporadic spinal cord examples
    • variants associated with NF-2

Management

  • Excision:
    • intramedullary examples generally curable2
    • few posterior fossa ependymomas can be completely resected due to colonization of bulbar tissues along floor of fourth ventricle

References

1 Wiestler OD, Schiffer D, Coons SW, Prayson RA, Rosenblum MK. Ependymal tumors. Kleihues P, Cavenee WK editor. World Health Organization classification of tumours. Pathology and genetics-tumours of the nervous system. Lyon: IARC Press; 2000.

2 Epstein FJ, Farmer JP, Freed D. Adult intramedullary spinal cord ependymomas. The result of surgery in 38 patients. J Neurosurg. 1993;79:204–209.

3 Little NS, Morgan MK, Eckstein RP. Primary ependymoma of a cranial nerve. Case report. J Neurosurg. 1994;81:792–794.

4 Guerrieri C, Jarlsfelt I. Ependymoma of the ovary. A case report with immunohistochemical, ultrastructural, and DNA cytometric findings, as well as histogenetic considerations. Am J Surg Pathol. 1993;17:623–632.

5 Duggan MA, Hugh J, Nation JG, Robertson DI, Stuart GC. Ependymoma of the uterosacral ligament. Cancer. 1989;64:2565–2571.

6 Nobles E, Lee R, Kircher T. Mediastinal ependymoma. Hum Pathol. 1991;22:94–96.

7 Crotty TB, Hooker RP, Swensen SJ, Scheithauer BW, Myers JL. Primary malignant ependymoma of the lung. Mayo Clin Proc. 1992;67:373–378.

8 Wiestler OD, Schiffer D, Coons SW, Prayson RA, Rosenblum MK. Ependymal tumors. Kleihues P, Cavenee WK editor. World Health Organization classification of tumours. Pathology and genetics-tumours of the nervous system. Lyon: IARC Press; 2000.

9 Afra D, Muller W, Slowik F, Wilcke O, Budka H, Turoczy L. Supratentorial lobar ependymomas. Reports on the grading and survival periods in 80 cases, including 46 recurrences. Acta Neurochir (Wien). 1983;69:243–251.

10 Craver RD, McGarry P. Delicate longitudinal nuclear grooves in childhood ependymomas. Arch Pathol Lab Med. 1994;118:919–921.

11 Brown DF, Chason DP, Schwartz LF, Coimbra CP, Rushing EJ. Supratentorial giant cell ependymoma. A case report. Mod Pathol. 1998;11:398–403.

12 Zec N, De Girolami U, Schofield DE, Scott RM, Anthony DC. Giant cell ependymoma of the filum terminale. A report of two cases. Am J Surg Pathol. 1996;20:1091–1101.

13 Mathews T, Moossy J. Gliomas containing bone and cartilage. J Neuropathol Exp Neurol. 1974;33:456–471.

14 Rosenblum MK, Erlandson RA, Aleksic SN, Budzilovich GN. Melanotic ependymoma and subependymoma. Am J Surg Pathol. 1990;14:729–736.

15 Takahashi H, Goto J, Emura I, Honma T, Hasegawa K, Uchiyama S. Lipidized (foamy) tumor cells in a spinal cord ependymoma with collagenous metaplasia. Acta Neuropathol (Berl). 1998;95:421–425.

16 Ruchoux MM, Kepes JJ, Dhellemmes P, Hamon M, Maurage CA, Lecomte M, et al. Lipomatous differentiation in ependymomas. A report of three cases and comparison with similar changes reported in other central nervous system neoplasms of neuroectodermal origin. Am J Surg Pathol. 1998;22:338–346.

17 Twiss JL, Anderson LJ, Horoupian DS. Globular glial fibrillary acidic protein-reactive cytoplasmic inclusions in ependymoma. An immunoelectron-microscopic study. Acta Neuropathol (Berl). 1993;85:658–662.

18 Sara A, Bruner JM, Mackay B. Ultrastructure of ependymoma. Ultrastruct Pathol. 1994;18:33–42.

19 Zuppan CW, Mierau GW, Weeks DA. Ependymoma with signet-ring cells. Ultrastruct Pathol. 1994;18:43–46.

20 Miettinen M, Clark R, Virtanen I. Intermediate filament proteins in choroid plexus and ependyma and their tumors. Am J Pathol. 1986;123:231–240.

21 Vege KD, Giannini C, Scheithauer BW. The immunophenotype of ependymomas. Appl Immunohistochem Mol Morphol. 2000;8:25–31.

22 Min KW, Scheithauer BW. Clear cell ependymoma. A mimic of oligodendroglioma. Clinicopathologic and ultrastructural considerations. Am J Surg Pathol. 1997;21:820–826.

23 Ang LC, Taylor AR, Bergin D, Kaufmann JC. An immunohistochemical study of papillary tumors in the central nervous system. Cancer. 1990;65:2712–2719.

24 Mannoji H, Becker LE. Ependymal and choroid plexus tumors. Cytokeratin and GFAP expression. Cancer. 1988;61:1377–1385.

25 Furness PN, Lowe J, Tarrant GS. Subepithelial basement membrane deposition and intermediate filament expression in choroid plexus neoplasms and ependymomas. Histopathology. 1990;16:251–255.

26 Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, et al. Prognostic factors in intracranial ependymomas in children. J Neurosurg. 2000;93:605–613.

27 Horn B, Heideman R, Geyer R, Pollack I, Packer R, Goldwein J, et al. A multi-institutional retrospective study of intracranial ependymoma in children. Identification of risk factors. J Pediatr Hematol Oncol. 1999;21:203–211.

28 Robertson PL, Zeltzer PM, Boyett JM, Rorke LB, Allen JC, Geyer JR, et al. Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children. A report of the Children's Cancer Group. J Neurosurg. 1998;88:695–703.

29 Prayson RA. Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. Ann Diagn Pathol. 1999;3:11–18.

Last updated: 11 Feb 2006

Ependymoma

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