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High-grade astrocytoma with piloid features (HGAP)

High-grade astrocytoma with piloid features (HGAP) is a rare, aggressive circumscribed astrocytic glioma that typically occurs in middle-aged to elderly adults, often in the posterior fossa (especially cerebellum), with strong association to neurofibromatosis type 1 and DNA-methylation profiling required for definitive WHO diagnosis.

Key Images

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(A) image of a 44-year-old man with midback pain shows a well-defined enhancing lesion involving the dorsal aspect of thoracic cord at the T9–T10 level (arrow). Postcontrast T1-weighted axial image in a 42-year-old man (B) shows tumor with peripheral irregular enhancement at the level of thalamus (arrow) with infratentorial pontomesencephalic and cerebellar involvement (not shown) along with diffuse intraventricular tumor seeding (arrowhead). Postcontrast T1-weighted sagittal (C) image of a 74-year-old-man with weakness and difficulty walking shows an intramedullary heterogeneously enhancing tumor involving nearly the entire cord C5–T1 (arrow) along with cord expansion. Postcontrast T1-weighted-axial (D) image in a 38-year-old man demonstrates a large multicystic lesion with peripheral enhancement in the left cerebellum (arrow).

44-year-old man (A) with dyspnea and vocal cord paralysis shows an expansile hyperintense lesion in the pontomedullary region with patchy ill-defined enhancement (not shown). Postcontrast T1-weighted axial MR images (not images). B, A 32-year-old woman presenting with hearing loss demonstrates a large, right pontine tumor extending into the right cerebellopontine angle, internal auditory canal, and prepontine cistern. Postcontrast T1-weighted axial MR images (C and D) demonstrate a midline, diencephalic/thalamic region tumor with rim enhancement in a 19-year-old man (C) and a 71-year-old woman (D).

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Look For First

Heterogeneously or peripherally enhancing posterior fossa/cerebellar mass in an adult, particularly with NF1 history
T1 hypo-/isointense and T2/FLAIR hyperintense signal with relatively circumscribed appearance
Absence of restricted diffusion (unusual for a high-grade glioma) is a key distinguishing feature

Key Image Findings

MRI signal: T1 hypo-/isointense, T2/FLAIR hyperintense with heterogeneous appearance and peripheral or heterogeneous enhancement pattern
Cystic and necrotic areas may be present with variable surrounding edema, but unlike most high-grade tumors, restricted diffusion is often absent or not dominant
Location predilection: 74% posterior fossa (especially cerebellum), with NF1-associated cases favoring midline structures including thalami
Spinal cord involvement (when present): intramedullary tumors often with exophytic components, typically affecting dorsal cord over long segments (>3 vertebral bodies)
Leptomeningeal and intraventricular dissemination can occur
No specific radiographic signature distinguishes HGAP from glioblastoma, high-grade pilocytic astrocytoma transformation, or diffuse midline glioma on imaging alone

Differential Diagnosis

Glioblastoma IDH-wildtype: typically shows more restricted diffusion and more aggressive enhancement; diagnosis confirmed by absence of HGAP methylation profile
Diffuse midline glioma: location and molecular profile differ; methylation class testing is mandatory to distinguish
High-grade transformation of pilocytic astrocytoma: prior benign pilocytic astrocytoma may precede HGAP, but HGAP defined by specific DNA-methylation class
Posterior fossa metastasis: clinical history and imaging location help distinguish; lack of restriction may be atypical for metastasis
Anaplastic pilocytic astrocytoma: histologic overlap is substantial; requires methylation profiling to confirm HGAP classification

Discussion

HGAP is defined not by imaging or histology alone but by characteristic DNA-methylation profile (WHO 2021 CNS classification), making integrated molecular workup mandatory for definitive diagnosis

Molecular hallmarks include MAPK-pathway activation (NF1, BRAF, FGFR1 alterations in ~75%), CDKN2A/B homozygous deletion (~80%), and ATRX mutation/loss (~45%), with IDH-wildtype status typical

The combination of loss of ATRX staining and CDKN2A/B homozygous deletion in a high-grade piloid tumor should strongly prompt methylation-class testing

Prognosis is poor with ~50% 5-year survival, intermediate between glioblastoma IDH-wildtype (worse) and IDH-mutant gliomas (better)

MAPK-pathway alterations create a rationale for molecularly directed therapy (mTOR and MAPK inhibitors) in selected progressive or recurrent tumors

Treatment approach: maximal safe surgical resection followed by concurrent chemoradiotherapy (e.g., temozolomide); no tumor-specific standard therapy currently exists

Reporting Pearls

For an adult posterior-fossa mass, report as: "Heterogeneously enhancing cerebellar/posterior-fossa astrocytic tumor with circumscribed appearance [and/or piloid morphology on preliminary pathology if available]. Given appearance and/or NF1 association, recommend integrated molecular workup including CDKN2A/B, ATRX, MAPK-pathway alterations, and DNA-methylation profiling to assess for high-grade astrocytoma with piloid features (HGAP)."

Pitfalls

Absence of restricted diffusion can lead to underestimation of grade; HGAP often lacks the high diffusion restriction typical of glioblastoma, potentially causing diagnostic delay
Histologic diagnosis of 'high-grade glioma with piloid features' is insufficient without methylation-class profiling; molecular confirmation is mandatory for HGAP classification
Confusing HGAP with recurrent or transformed pilocytic astrocytoma; prior benign pilocytic astrocytoma may precede HGAP, requiring methylation profiling to confirm aggressive transformation
Imaging appearance is nonspecific and overlaps substantially with glioblastoma, diffuse midline glioma, and metastasis; clinical context (NF1 history, posterior fossa location, age) should prompt suspicion and molecular workup