—  SPECIALTY CONFERENCE  —

Neuropathology

Case 1 - Chordoid Glioma

Daniel J. Brat
Emory University Hospital
Atlanta, Georgia


Click on each slide thumbnail image for an enlarged view
Clinical History:
Over a period of 6 months, a 31-year-old female developed headaches, nausea and vomiting and experienced short periods of unconsciousness. An MRI scan revealed a homogeneously contrast-enhancing tumor in the third ventricle, measuring 3 cm in greatest diameter, which appeared to arise in the hypothalamic/suprasellar region.

Diagnosis - Chordoid Glioma


Case 1 - Figure 1 - Chordoid glioma of the third ventricle. T1-weighted magnetic resonance image following contrast injection demonstrating a sharply demarcated, solid and homogeneously enhancing mass in the third ventricle.
Case 1 - Figure 2 - Chordoid glioma of the third ventricle. Cords of epithelioid tumor cells are disposed in a basophilic, myxoid matrix.


Case 1 - Figure 3 - Chordoid glioma of the third ventricle. Note conspicuous lymphoplasmacellular infiltration of the lesion - a consistent histologic feature of chordoid gliomas.
Case 1 - Figure 4 - GFAP - Chordoid glioma of the third ventricle. As demonstrated in this immunohistochemical preparation, chordoid gliomas exhibit diffuse cytoplasmic labeling for glial fibrillary acidic protein.

Discussion
Chordoid glioma is a recently recognized central nervous system (CNS) neoplasm that occurs exclusively in the region of the third ventricle and hypothalamus.1  They typically present in adulthood, between the ages of 30 and 70-years, and are more common in women. Only a single case of pediatric chordoid glioma has been described.2  Symptoms are most often due to compression of adjacent normal structures in the region and include visual disturbance and endocrine dysfunction. Headache, nausea and ataxia can follow obstructive hydrocephalus.

Histopathologically, these lesions are composed of cords and clusters of epithelioid tumor cells embedded in a mucinous matrix, giving a 'chordoid' appearance. Tumor cells are uniform, moderate in size, have abundant pink cytoplasm, and oval, bland nuclei. Nuclear atypia and mitotic activity are generally lacking. More typical are relative circumscription with regard to surrounding brain, a prominent lymphoplasmacytic infiltrate within the tumor stroma, and Russel bodies. By imuunohistochemistry, tumor cells are strongly reactive for GFAP and S-100 protein. EMA staining is usually absent or focal.

Chordoid gliomas are usually difficult to totally resect, both because of their location and their physical association with hypothalamic structures. Complete resection can be accompanied by hypothalamic injury and poor postoperative outcome. Incompletely resected tumors usually recur, even following radiation therapy.

The 2000 World Health Organization (WHO) Classification of CNS neoplasms included chordoid glioma as a distinct entity and has provisionally assigned it as WHO grade II.3  Acceptance by the WHO will certainly lead to better recognition and understanding of these uncommon lesions. Recent neuroradiologic, ultrastructural, and genetic investigations have rounded out our current conception. In the most comprehensive genetic investigation, Reifenberger et al., analyzed molecular genetic and chromosomal abnormalities in chordoid gliomas by polymerase chain reaction (PCR)-based techniques, DNA sequencing, and comparative genomic hybridization (CGH).4  No consistent chromosomal imbalances were detected in any of these tumors by CGH. Analysis of p53, p16 (CDKN2A), EGFR, CDK4, and MDM2-genes that are frequently altered in infiltrative forms of astrocytomas-did not reveal any mutations, deletions, or amplifications. The paucity of chromosomal structural abnormalities in these lesions is most likely due to their low grade, while the lack of genetic alterations typical of astrocytomas probably reflects the unique histogenesis of chordoid gliomas.

One of the most peculiar features of chordoid glioma is their predilection for the region of the third ventricle and hypothalamus. Cenacchi et al., investigated the ultrastructural features of these neoplasms and were able to hypothesize a 'cell or origin' for chordoid glioma that might explain its regional specificity.5  The authors found evidence of ependymal differentiation (microvilli and hemidesmosome-like structures) but also a cytologic zonation pattern and secretory vesicles that were more suggestive of specialized ependymal cells of the subcommisural organ. This specialized structure is more prominent during development and is located in the dorsocaudal region of the third ventricle. The specificity of chordoid glioma to the third ventricular region may be explained by the unique anatomic location of a neoplastic precursor population in the subventricular region of the third ventricle. Further evidence of ependymal or specialized-ependymal differentiation has come from a recent report which demonstrated abnormal cilia in a juxtanuclear location.6 

Lastly, the neuroimaging properties of chordoid gliomas have recently been defined.7  Lesions are typically solid, round-to-ovoid, well-circumscribed, contrast-enhancing masses of the hypothalamus and anterior third ventricle. They are generally isointense to brain on T1-weighted MRI and slightly hyperintense on T2-weighted imaging. Mass effect from the lesions is most often distributed symmetrically and causes vasogenic edema (T2-weighted hyperintensity) in compressed adjacent CNS structures. The lesions studied had physical continuity with the hypothalamus and some appeared to have an intrinsic component within this structure, suggesting a potential site of origin.

References

  1. Brat DJ, Scheithauer BW, Staugaitis SM, Cortez SC, Brecher K, Burger PC. Third ventricular "chordoid glioma": a distinct clinicopathologic entity. J. Neuropathol. Exp. Neurol. 1998;57:283-90.
  2. Castellano-Sanchez AA, Schemankewitz E, Mazewski C, Brat DJ. Pediatric chordoid glioma with chondroid metaplasia. Pediatr Dev Pathol. 2001;4:564-7.
  3. Brat DJ, Scheithauer BW, Cortez SC, Reifenberger G, Burger PC. Chordoid glioma of the third ventricle. In Kleihuis P. and Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2nd ed. Lyon: Intl. Agency for Research, 2000.
  4. Reifenberger G, Weber T, Weber RG, Wolter M, Brandis A, Kuchelmeister K, Pilz P, Reusche E, Lichter P, Wiestler OD. Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity. Brain Pathol. 1999;9:617-26.
  5. Cenacchi G, Roncaroli F, Cerasoli S, Ficarra G, Merli GA, Giangaspero F. Chordoid glioma of the third ventricle: an ultrastructural study of three cases with a histogenetic hypothesis. Am J Surg Pathol. 2001;25:401-5.
  6. Pasquier B, Peoc'h M, Morrison AL, Gay E, Pasquier D, Grand S, Sindou M, Kopp N. Chordoid glioma of the third ventricle: a report of two new cases, with further evidence supporting an ependymal differentiation, and review of the literature. Am J Surg Pathol. 2002;26:1330-42.
  7. Pomper MG, Passe TJ, Burger PC, Scheithauer BW, Brat DJ. Chordoid glioma: a neoplasm unique to the hypothalamus and anterior third ventricle. AJNR Am J Neuroradiol. 2001;22:464-9.