High-grade astrocytoma with piloid features

High-grade astrocytoma with piloid features
Diagnosis in short
High-grade astrocytoma with piloid features. H&E stain.
LM DDx	astrocytoma, PXA, glioblastoma
Stains	PAS-D +ve (eosinophilic granular bodies)
IHC	GFAP +ve
Gross	usually cerebellar
Site	brain - usu. cerebellum
Prevalence	very rare - esp. in children
Prognosis	poor (analog to WHO Grade III)

High-grade astrocytoma with piloid features (HGAP) is a rare glial tumor which often requires methylation analyis to secure diagnosis. There is currently no definitive grading, but clinical behaviour suggests WHO CNS grade 3.

Clinical

• Rare (1-3% of all brain tumor in adults).
• Usu. posterior fossa (75%).
• Supratentorial or spinal locations possible.
• Imaging may be similiar to Glioblastoma.
• 5-year OS: 50%.
• De novo cases in the setting of neurofibromatosis 1 reported.
• Tumors may have history of previous radiation.

Histology

• Often so variable, so molecular testing is essential to secure diagnosis.
• Astrocytic nature of tumor cells.
• Frequent mitoses.
• Elongated glial tumor cell processes ("piloid").
• Rosenthal fibers or eosinophilic granular bodies.
• Perivascular lymphocytic cuffing.
• Necrosis may be present.

Images

• 

  HGAP, FFPE specimen, HE (WC).

• 

  Vacular proliferations and necrosis in HGAP mimicking GBM (WC).

IHC

• GFAP+ve.
• ATRX: nuclear loss in approx. 40%.

Molecular

• DNA Methylation profile of high-grade astrocytoma with piloid features is essential for diagnosis.
• MAPK genes often altered (NF1, BRAF fusion, FGFR1, KRAS).
• CDKN2A/B homozygous deletion.
• CDK4 amplification.
• TERT promotor mutations are rare.
• Absence of IDH1/2 hotspot mutation.

Prognosis

• Poor, but better than conventional glioblastoma.
• Prognostic unfavourable paramters include: Necrosis, Mitoses and previous radiation.

DDx:

• Glioblastoma
• Pleomorphic xanthoastrocytoma

See also

• Astrocytoma.
• Neuropathology_tumours#Infiltrative_astrocytomas