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Other astrocytic tumors

High grade astrocytoma with piloid features (HGAP)



Last author update: 13 May 2024
Last staff update: 13 May 2024

Copyright: 2024, PathologyOutlines.com, Inc.

PubMed Search: High grade astrocytoma with piloid features

Antonio d’Amati, M.D.
Manila Antonelli, M.D., Ph.D.
Page views in 2024 to date: 612
Cite this page: d'Amati A, Gianno F, Antonelli M. High grade astrocytoma with piloid features (HGAP). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/CNStumorHGAP.html. Accessed July 14th, 2024.
Definition / general
  • Circumscribed astrocytic glioma with high grade piloid or glioblastoma-like histological features and distinct DNA methylation profile
Essential features
  • Recently recognized entity, included in the 2021 WHO classification of CNS tumors
  • Circumscribed astrocytic glioma occurring throughout the entire CNS, mostly in the posterior fossa
  • High grade histological features associated with piloid or glioblastoma-like morphology
  • Distinct DNA methylation profile and MAPK pathway gene alterations, often associated with homozygous deletion (HD) of CDKN2A / CDKN2B or ATRX alterations
  • CNS WHO grade currently not assigned (clinical behavior roughly similar to CNS WHO grade 3)
Terminology
  • Anaplastic astrocytoma with piloid features (not recommended by CNS WHO 2021)
ICD coding
  • ICD-O: 9421/3 - high grade astrocytoma with piloid features
  • ICD-11: 2A00.0Y & XH6PH6 - other specified gliomas of brain & astrocytoma, NOS
Sites
Pathophysiology
  • Cell of origin is currently unknown
  • 3 pathways are probably involved in the pathogenesis (Acta Neuropathol 2018;136:273)
    • MAPK pathway gene alterations are likely the initiating event (driver mutation)
    • Deregulation of retinoblastoma tumor suppressor protein cell cycle pathway by CDKN2A / CDKN2B inactivation (homozygous deletion) or occasionally CDK4 amplification
    • Activation of telomere maintenance by ATRX alterations and rarely TERT promoter mutations
  • Numerous chromosomal alterations and frequent structural aberrations (Acta Neuropathol 2018;136:273)
    • Partial gains of 12q and 17q
    • Losses of 1p and 8p
    • Partial losses of 14 and 19q
Etiology
Clinical features
  • Clinical signs and symptoms depend on tumor location
Diagnosis
  • Magnetic resonance imaging (MRI), followed by stereotactic brain biopsy or surgical resection
  • CNS WHO 2021 diagnostic criteria
    • Essential
      • Histological aspect of an astrocytic glioma
      • DNA methylation profile of HGAP
    • Desirable
      • MAPK pathway gene alteration
      • CDKN2A / CDKN2B HD or CDK4 amplification
      • ATRX mutation or loss of nuclear expression
      • Anaplastic histological features
Radiology description
Radiology images

Contributed by Antonio d'Amati, M.D.
T2 MRI of brain

T2 MRI of brain

T1 MRI of brain

T1 MRI of brain

Coronal FLAIR MRI of brain

Coronal FLAIR MRI of brain

Sagittal FLAIR MRI of brain

Sagittal FLAIR MRI of brain

Prognostic factors
  • Prognostic data are currently limited to a single retrospective study (Acta Neuropathol 2018;136:273)
    • 5 year overall survival: 50%
    • No prognostic association with high grade histological features (e.g., mitoses or necrosis)
    • No prognostic association with MGMT promoter methylation status
  • CNS WHO grade currently not assigned (clinical behavior roughly similar to CNS WHO grade 3)
Case reports
Treatment
Gross description
  • Mostly well demarcated solid lesion
  • Areas of cystic degeneration, necrosis or hemorrhage may be variably present
Gross images

Contributed by Antonio d'Amati, M.D.
Cerebellar surgical resection

Cerebellar surgical resection

Microscopic (histologic) description
  • Histological features are very variable and not sufficient for diagnosis, without additional molecular testing
  • Astrocytic glioma, with moderate cell density
  • Predominantly solid / circumscribed tumor growth but possible invasion into the adjacent parenchyma
  • Growth patterns (Acta Neuropathol 2018;136:273)
    • Glioblastoma-like
    • Pleomorphic xanthoastrocytoma-like
    • Pilocytic astrocytoma-like (cells with hair-like piloid cytoplasmic processes)
  • Eosinophilic granular bodies or Rosenthal fibers (~30% of cases) (Acta Neuropathol 2018;136:273)
  • High grade histological features
Microscopic (histologic) images

Contributed by Francesca Gianno, M.D., Ph.D.
Piloid features

Piloid features

Spindle cells

Spindle cells

Sheets of cells

Sheets of cells

Rosenthal fibers Rosenthal fibers

Rosenthal fibers


Eosinophilic granular bodies

Eosinophilic granular bodies

Pleomorphic cells

Pleomorphic cells

Myxoid background Myxoid background

Myxoid background

GFAP

GFAP


Olig2

Olig2

ATRX

ATRX

Low Ki67

Low Ki67

High Ki67

High Ki67

p16

p16

Virtual slides

Contributed by Francesca Gianno, M.D., Ph.D. and Antonio d'Amati, M.D.
Surgical resection of cerebellar lesion with piloid features

Cerebellar lesion with piloid features

Surgical resection of cerebellar lesion with GBM-like appearance

Cerebellar lesion with GBM-like appearance

Positive stains
Negative stains
Electron microscopy description
  • Not routinely used for diagnostic purposes
Molecular / cytogenetics description
Molecular / cytogenetics images

Contributed by Simone Minasi, Ph.D. and Francesca Romana Buttarelli, Ph.D.
CDKN2A homozygous deletion

CDKN2A homozygous deletion

KIAA1549::BRAF fusion

KIAA1549::BRAF fusion



Images hosted on other servers:
TSNE analysis of DNA methylation data

DNA methylation data

H&E stainings and copy number plots

Copy number plots

Sample pathology report
  • Brain, cerebellum, resection:
    • Integrated diagnosis: high grade astrocytoma with piloid features (HGAP)
    • Histologic diagnosis: astrocytic glioma, with high grade histologic features
    • Immunohistochemical results
      • GFAP+
      • Olig2+
      • IDH1 R132H-
      • Loss of ATRX nuclear expression
      • Ki67: 10%
    • CNS WHO grade: not assigned
    • Molecular information
      • DNA methylation class: HGAP (score 0.99)
      • NF1 mutation
      • CDKN2A homozygous deletion
Differential diagnosis
Board review style question #1

A 43 year man has a cerebellar mass. Histologic features are shown in the image above. Immunohistochemistry revealed IDH1 R132H negativity and loss of ATRX nuclear expression. Molecular analyses only revealed NF1 mutation and CDKN2A homozygous deletion. What is the most likely diagnosis?

  1. Ganglioglioma
  2. Glioblastoma, IDH wild type
  3. High grade astrocytoma with piloid features (HGAP)
  4. Pilocytic astrocytoma
  5. Pleomorphic xanthoastrocytoma
Board review style answer #1
C. High grade astrocytoma with piloid features (HGAP). The image shows an astrocytic glioma, with piloid aspects and high grade histologic features. Answer D is incorrect because pilocytic astrocytomas with high grade histologic features (anaplastic PA) are uncommon in adult population; moreover, ATRX loss and CDKN2A homozygous deletion exclude this diagnosis. Answers B and E are incorrect because glioblastoma, IDH wild type and pleomorphic xanthoastrocytoma are uncommon in cerebellar locations and usually show preserved ATRX expression. Answer A is incorrect because ganglioglioma shows different clinical, histological, immunohistochemical and molecular features.

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Reference: High grade astrocytoma with piloid features (HGAP)
Board review style question #2
Which of the following is an essential molecular criterion to confirm a diagnosis of high grade astrocytoma with piloid features (HGAP)?

  1. ATRX alterations
  2. CDK4 amplification
  3. KIAA1549::BRAF fusions
  4. Specific DNA methylation profile
  5. TP53 mutations
Board review style answer #2
D. Specific DNA methylation profile. According to 2021 CNS WHO criteria, demonstration of DNA methylation profile is mandatory to confirm a diagnosis of HGAP. Answers A, B and C are incorrect because while ATRX alterations, KIAA1549::BRAF fusions and CDK4 amplification are reported at variable frequency in HGAP, these only represent desirable criteria. Answer E is incorrect because TP53 mutations are not commonly associated with HGAP.

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Reference: High grade astrocytoma with piloid features (HGAP)
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