Isomorphic diffuse glioma is an indolent low-grade diffuse glioma, often considered one of the long-term epilepsy-associated tumors (LEATs), closely related to pediatric diffuse astrocytoma MYB or MYBL1 altered but demonstrating distinct DNA-methylation profile 1. It is critical that these tumors are recognized rather than interpreted as an IDH-wildtype diffuse astrocytoma (the majority of which will be glioblastomas with commensurately poor prognosis).
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Terminology
Isomorphic diffuse gliomas, at times also referred to as isomorphic neuroepithelial tumors, are not yet included in the current (2021) WHO classification of CNS tumors and are currently loosely contained within the diagnosis of diffuse astrocytoma MYB or MYBL1 altered despite different epidemiology and DNA-methylation profile 1,2.
Epidemiology
Isomorphic diffuse gliomas tend to arise in children and young adults 1,2.
Clinical presentation
Although most isomorphic diffuse gliomas have historically been diagnosed in young adults, they typically present with seizures in childhood 1,2.
Pathology
Microscopic appearance
Generally, isomorphic diffuse gliomas appear as well-differentiated, low to moderately cellular glial neoplasms. They are comprised of astrocytes with infrequent or absent mitoses. The neoplastic cells have small, round nuclei with regular chromatin 1.
Immunohistochemisty
GFAP: positive 2
IDH R132H: negative
MAP2: negative
OLIG2: negative
CD34: negative
ATRX-expression: retained
Genetics
MYBL1 alterations (e.g. gene fusions) 2; or
MYB alternation (less common)
IDH wildtype 2
distinct DNA-methylation profile closely related to diffuse astrocytoma MYB or MYBL1 altered and angiocentric gliomas 1
Grading
Although these tumors are not yet formally included in WHO classification of CNS tumors (2021) they generally behave in an indolent fashion, similar to other WHO CNS grade 1 tumors 1.
Radiographic features
MRI
MRI is the modality of choice for assessing tumors in the setting of refractory epilepsy. The features are relatively non-specific 2. Typically located in the supratentorial brain and appear as quite well circumscribed lesions a few centimeters in diameter 1,2.
T1: hypointense
T1 C+: no enhancement
T2/FLAIR: hyperintense
Treatment and prognosis
Surgical resection is curative and the vast majority of patients (89%) becoming seizure-free after surgery 2.