Glioblastoma IDH wildtype and demyelination

Within the left superior temporal gyrus, there is a rim-enhancing lesion - localizing to a grey-white interface rather than the cortex. The lesion is heterogeneous on T1 and T2 weighted sequences with moderate diffusion restriction identified throughout. On susceptibility imaging, a complete hypointense rim is not identified. There is increased rCBV within the enhancing portion of the lesion.

Spectroscopy demonstrates elevated lactate peak and markedly depressed NAA within the non-enhancing central portion of the lesion. At the periphery of the lesion, there is moderate NAA reduction, but choline peak assessment is limited by a wandering baseline.

There is extensive surrounding white matter T2 hyperintensity in keeping with vasogenic edema. There is resultant mass-effect with effacement of the left temporoparietal sulci and minor effacement of the left lateral ventricle. No hydrocephalus or midline shift. The basal cisterns are preserved.

No other lesion identified.

Conclusion:

Peripherally enhancing mass within the left superior temporal gyrus with surrounding vasogenic edema. The main differential is between metastasis and GBM.

Although there is diffusion restriction of the lesion, this is not isolated to the central non-enhancing component, and the thick irregular rind favors tumor over abscess.

MICROSCOPIC DESCRIPTION:

The sections show densely hypercellular tissue fragments composed of a mixture of CD68+ monocyte macrophages and astrocytic cells which show moderate to marked nuclear and cellular pleomorphism. Both cell types are arranged in diffuse sheets. There is prominent microvascular proliferation with multilayering of endothelial cells which also show nuclear and cellular pleomorphism. Endothelial cell mitoses are noted.

There are a moderate number of Creutzfeldt astrocytes. Mitotic figures are identified in atypical atrocytic cells. A fragment of necrotic tissue is present with neutrophilic infiltration of the immediately adjacent viable tissue. Collections of CD3+ lymphocytes are noted within and adjacent to the walls of some blood vessels. Extensive loss of myelin is identified in a Luxol Fast Blue stained section and granular LFB+ material is seen in the cytoplasm of macrophages. Preservation of axons is seen in a Bodian stained section.

IMMUNOHISTOCHEMISTRY:

• GFAP positive in atypical and reactive astrocytes and
• Creutzfeldt cells.
• Nestin positive
• IDH-1 negative
• p53 positive
• p16 negative

Topoisomerase labeling index: Approximately 12%

FINAL DIAGNOSIS:

Left temporal lesion: Features favoring glioblastoma multiforme (WHO Grade IV) 

COMMENT:

These are difficult biopsies to interpret with apparent overlapping features of demyelination (loss of myelin on Luxol Fast Blue staining, axonal preservation, perivascular T lymphocyte aggregation; the presence of Creutzfeldt astrocytes) and high-grade astrocytoma (astrocyte pleomorphism, mitotic figures, microvascular proliferation and necrosis).

Note: Although this tumor is entirely consistent with IDH wild-type molecular subtype, strictly speaking, to conclusively establish this, IDH would need to be sequenced to ensure that a non-IDH1 R132H mutation was present. In practice, an IDH1 R132H negative tumor in an individual over 55-years-of-age makes the possibility of this being IDH mutant remote (<1%), and sequencing is not felt to be necessary by many institutions, and not recommended by the WHO classification of CNS tumors (2016).