Diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype

Diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype are high-grade pediatric tumors recently included in the 5^th Edition (2021) of the WHO brain tumor classification.

Terminology

Diffuse pediatric-type high-grade gliomas H3-wildtype and IDH-wildtype are classified among the "pediatric-type diffuse high-grade gliomas" (WHO grade 4). 

Pathology

Subtypes

Three subtypes of diffuse pediatric-type high-grade gliomas H3-wildtype and IDH-wildtype have been identified on the basis of specific molecular alterations ¹:

• diffuse pediatric-type high-grade glioma RTK2

• diffuse pediatric-type high-grade glioma RTK1

• diffuse pediatric-type high-grade glioma MYCN

Location

The location depends on subtype ²:

• diffuse pediatric-type high-grade glioma RTK2:

  • supratentorial (96%)

  • infratentorial (4%)

• diffuse pediatric-type high-grade glioma RTK1:

  • supratentorial (82%)

  • infratentorial (18%)

• diffuse pediatric-type high-grade glioma MYCN:

  • supratentorial (86%)

  • infratentorial (14%)

Microscopic appearance

Diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype demonstrate glioblastoma-like features with high cellularity, brisk mitotic activity, microvascular proliferation and necrosis. They may also display sometimes an undifferentiated morphology ^3,4.

Radiographic features

Diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype are similar to other high-grade gliomas. 

On MRI, they may appear as lesions with well-defined margins, homogeneous contrast-enhancement and mild perilesional edema ^1,3,4.

Treatment and prognosis

Treatment of diffuse pediatric-type high-grade gliomas H3-wildtype and IDH-wildtype consists of gross total or subtotal tumor resection followed by radiotherapy and chemotherapy. They usually have a poor prognosis with a median overall survival of 17.2 months ⁵. However median overall survival may vary among the different subtypes ²:

• diffuse pediatric-type high-grade glioma RTK1 ( 21 months)

• diffuse pediatric-type high-grade glioma RTK2 (44 months)

• diffuse pediatric-type high-grade glioma MYCN (14 months)

Differential diagnosis

• infant-type hemispheric glioma

• desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma

• pleomorphic xanthoastrocytoma

• CNS embryonal tumors:

  • atypical teratoid/rhabdoid tumor
  • cribriform neuroepithelial tumor (provisional inclusion)
  • embryonal tumor with multilayered rosettes (ETMR)
  • CNS neuroblastoma, FOXR2-activated
  • CNS tumor with BCOR internal tandem duplication
  • CNS embryonal tumor

• medulloblastoma

• diffuse midline glioma, H3 K27-altered

• diffuse hemispheric glioma, H3 G34-mutant

• infant-type hemispheric glioma