Recent work has demonstrated that nearly all diffuse
gliomas display nuclear immunoreactivity for the
bHLH transcription factor OLIG2, and the R132H mutant
isocitrate dehydrogenase 1 (IDH1)
protein is expressed in the majority of diffuse
gliomas other than primary
glioblastoma. However, these
antibodies have not been widely applied to rarer
glioblastoma variants, which can be diagnostically challenging when the astrocytic features are subtle. We therefore surveyed the expression patterns of OLIG2 and IDH1 in 167 non-conventional
glioblastomas, including 45 small cell
glioblastomas, 45
gliosarcomas, 34
glioblastomas with
primitive neuroectodermal tumor-like foci (
PNET-like foci), 23 with an oligodendroglial component, 11 granular cell
glioblastomas, and 9
giant cell glioblastomas. OLIG2 was strongly expressed in all
glioblastomas with oligodendroglial component, 98% of small cell
glioblastomas, and all granular cell
glioblastomas, the latter being particularly helpful in ruling out macrophage-rich lesions. In 74% of
glioblastomas with
PNET-like foci, OLIG2 expression was retained in the
PNET-like foci, providing a useful distinction from central nervous system
PNETs. The glial component of
gliosarcomas was OLIG2 positive in 93% of cases, but only 14% retained focal expression in the sarcomatous component; as such this marker would not reliably distinguish these from pure
sarcoma in most cases. OLIG2 was expressed in 67% of
giant cell glioblastomas. IDH1 was expressed in 55% of
glioblastomas with oligodendroglial component, 15% of
glioblastomas with
PNET-like foci, 7% of
gliosarcomas, and none of the small cell, granular cell, or
giant cell glioblastomas. This provides further support for the notion that most
glioblastomas with oligodendroglial component are secondary, while small cell
glioblastomas, granular cell
glioblastomas, and
giant cell glioblastomas are primary variants. Therefore, in one of the most challenging differential diagnoses, IDH1 positivity could provide strong support for
glioblastoma with oligodendroglial component, while essentially excluding small cell
glioblastoma.