Diffuse low-grade glioma, MAPK pathway-altered

View Details

Status

Done

Definition

Essential:

Diffuse glioma with absent or minimal mitotic activity and neither microvascular proliferation nor necrosis AND
Genetic alteration in the МАРК pathway AND
IDH-wildtype and H3-wildtype AND
Absence of homozygous deletion of CDKN2A

Desirable:

Onset in childhood, adolescence, or early adulthood
Absence of morphological features or DNA methylation profile suggestive of an alternative tumour type in which FGFR or BRAF abnormalities occur

Numbers

Rare

Molecular marker

IDH wildtype

H3 wildtype

Without homozygous deletion of CDKN2A

Numbers

Typically occur in the paediatric population

Localisation

Throughout the craniospinal axis

Esp cerebral hemisphere

Among paediatric low-grade gliomas, specific alterations are more common in specific locations

Pathology/Genetic

Genetics Subtypes

FGFR1 tyrosine kinase domain (TDK)-duplicated AND FGFR1-mutant

Morphological features of an oligodendroglioma
Mitotic activity is rare or absent, and there is no microvascular proliferation or necrosis
Immunopositive for OLIG2 and show variable expression of GFAP
Differential diagnosis

Dysembryoplastic neuroepithelial tumour

Dysembryoplastic neuroepithelial tumours can only be distinguished by the presence of their defining specific giioneuronal element and, in complex cases, glial nodules.

PLNTY

Distinctive cytology and show widespread strong expression of CD34.

Adult-type IDH-mutant oligodendroglioma

Distinguished by the presence of an IDH mutation combined with 1p/19q codeletion

BRAF p.V600E-mutant

Composed of well-differentiated glial cells with bland, ovoid to spindle-shaped nuclei and fine fibrillary processes

Neither Rosenthal fibres nor eosinophilic granular bodies are typically found

Mitotic figures are or absent, and there is no microvascular proliferation or necrosis

Immuno-positive for

OLIG2 and GFAP, which highlights the fine cell processes
BRAF p.V600E illustrates the BRAF mutation

Differential diagnosis

Pilocytic astrocytoma,
Ganglioglioma,
Pleomorphic xanthoastrocytoma
Important to exclude IDH-mutant and H3 K27-altered diffuse midline gliomas, which can have histopathological features identical to those of a BRAF p.V600E-mutant diffuse low-grade glioma

A collage of images of cells AI-generated content may be incorrect. — Diffuse low-grade glioma, MAPK pathway-altered. A low-grade diffuse glioma of moderate cellularity (A) entrapping normal neurons (B) and showing subpial aggregation (C), typical of diffuse gliomas. The tumour cells have a bland appearance and are mildly atypical (B, D).

Clinical presentation

Epilepsy

Radiology

May have a more diffuse picture with T2-FLAIR than do pilocytic astrocytomas

A close-up of a brain AI-generated content may be incorrect. — Diffuse low-grade glioma, MAPK pathway-altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with low T1 signal (A), high T2 signal (B), and heterogeneous enhancement with a cystic element on postcontrast T1-weighted imaging (C).

Outcome

The underlying mutation is likely to have an impact on outcome.

Bag et al. showed that diffuse low-grade glioma, FGFR1 TKD duplicated has a better outcome compared with diffuse low-grade glioma FGFR1-mutant with 5-year progression-free survival rates of

FGFR1 TKD duplicated: 69%
FGFR1-mutant: 53%

Currently, it is not known to which extent this group will be categorised into further discrete tumour types and prognostic factors related to the group will most likely elucidated as the molecular classification of this group is further studied.

Made with Bullet