CNS tumor
Diffuse astrocytic and oligodendroglial tumors
Diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma


Minor changes: 8 July 2020

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PubMed Search: Diffuse astrocytic glioma IDH (wild type OR wildtype) molecular features glioblastoma

John DeWitt, M.D., Ph.D.
Page views in 2020 to date: 1,660
Cite this page: DeWitt J. Diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumordiffuseastrocyticglioma.html. Accessed October 24th, 2020.
Definition / general
  • cIMPACT-NOW (Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) working group definition: histologic grade II or grade III IDH wildtype diffuse astrocytic gliomas that contain high level EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (+7 / -10) or TERT promoter mutations
Essential features
  • Tumor must be a diffusely infiltrating glioma
  • Confirmation of IDH wildtype status is essential (sequencing of IDH1/2 necessary in cases with negative R132H-IDH1 immunohistochemistry)
  • Evidence of EGFR amplification, +7 / -10 chromosome gain or loss or TERT promoter mutation is required
  • Based on studies examining IDH wildtype diffuse or anaplastic astrocytomas that would be considered WHO grade II or III based on histologic criteria (no microvascular proliferation or necrosis), those harboring the above specific molecular alterations have an aggressive clinical course, with overall patient survival times equivocal equivalent to that of IDH wildtype glioblastoma, WHO grade IV (N Engl J Med 2015;372:2481, N Engl J Med 2015;372:2499, Acta Neuropathol 2010;120:707, Acta Neuropathol 2015;129:679, Neuro Oncol 2019 Oct 22 [Epub ahead of print])
  • Therefore, this entity would be expected to be similar to glioblastoma, IDH wildtype, WHO grade IV with respect to clinical and histologic features
Terminology
  • Molecular GBM (glioblastoma)
ICD coding
  • ICD-10: C71.9 - Malignant neoplasm of brain, unspecified
Radiology description
  • Although a WHO grade IV tumor, imaging in diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma may not show the heterogeneous enhancement typical of histologic glioblastoma, as the underlying histologic correlate of enhancement, microvascular proliferation and necrosis may not be present
  • Alternatively, in cases of undersampled tumors such as on a small stereotactic biopsy, imaging may show the typical heterogeneous enhancement of glioblastoma, IDH wildtype but the histologic features of glioblastoma are not present on the sampled tissue, necessitating WHO grade IV diagnosis on molecular grounds through a diagnosis of diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma
Diagnosis
  • Molecular studies confirming the presence of EGFR amplification, +7 / -10 or TERT promoter mutation would be necessary in the diagnostic work up
Molecular / cytogenetics description
  • IDH wildtype status by either R132H-IDH1 immunohistochemistry or IDH1/2 sequencing
  • Molecular testing including FISH, chromosome analysis shows the presence of EGFR amplification, +7 / -10 or TERT promoter mutation
Sample pathology report
  • Brain, right frontal, biopsy:
    • Diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma, WHO grade IV (see comment)
  • Comment:
    • Integrated diagnosis:
      • Diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma, WHO grade IV
    • Histologic diagnosis:
      • Anaplastic astrocytoma
    • Integrated histologic and molecular grade:
      • IV of IV
    • Molecular information:
      • IDH:
        • Wildtype (R132H-IDH immunohistochemistry and IDH1/2 sequencing)
        • ATRX: retained (immunohistochemistry; consistent with wildtype)
        • P53: few positive (immunohistochemistry; consistent with wildtype)
        • EGFR: amplification present (FISH)
    • The specimen consists of brain infiltrated by hyperchromatic and moderately pleomorphic astrocytic tumor cells. Scattered mitoses are present, however, microvascular proliferation or necrosis are not seen. Given the presence of EGFR amplification, the findings are consistent with diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma, WHO grade IV (Acta Neuropathol 2018;136:805).
Differential diagnosis
Additional references
Board review style question #1
    You are reviewing a biopsy of a right frontal intraaxial mass from a 59 year old man. Histologic review shows an infiltrating glioma with significant pleomorphism and scattered mitotic activity but no microvascular proliferation or necrosis. NGS sequencing panel is negative for mutations in IDH1 or IDH2 and shows the presence of a TERT promoter mutation. Which of the following is the correct histologic grade and integrated diagnostic grade, respectively?

  1. III, III
  2. III, IV
  3. IV, III
  4. IV, IV
Board review style question #2
    You are reviewing a biopsy of a left frontal intraaxial mass from a 67 year old woman. Histologic review shows an infiltrating glioma with significant pleomorphism and scattered mitotic activity but no microvascular proliferation or necrosis. The presence of what alteration on subsequent molecular studies would be sufficient for a diagnosis of diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma, WHO grade IV?

  1. Chromosome +7 / -10
  2. IDH1/2 mutation
  3. PDGFRA amplification
  4. TP53 mutation
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