Case 1 -
Daniel J. Brat
Emory University Hospital
Click on each slide thumbnail image for an enlarged view
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
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.
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
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.
- 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.
- Castellano-Sanchez AA, Schemankewitz E, Mazewski C, Brat DJ. Pediatric chordoid glioma with
chondroid metaplasia. Pediatr Dev Pathol. 2001;4:564-7.
- 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.
- 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.
- 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.
- 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.
- 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.