CNS & pituitary tumors
Gliomas, glioneuronal tumors and neuronal tumors
Pediatric type diffuse high grade gliomas
Infant type hemispheric glioma
Editorial Board Member: Jared T. Ahrendsen, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Last author update: 21 October 2024
Last staff update: 21 October 2024
Copyright: 2023-2024, PathologyOutlines.com, Inc.
PubMed Search: Infant type hemispheric glioma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Stathas S, Zanazzi G. Infant type hemispheric glioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/CNStumorinfanttype.html. Accessed November 28th, 2024.
Definition / general
- High grade, typically hemispheric, hypercellular glioma arising in infancy
- These tumors have a distinct DNA methylation signature and typically contain receptor tyrosine kinase fusions, particularly those in the NTRK family or in ROS1, ALK or MET
Essential features
- Presents during infancy and usually arises in the cerebral hemispheres
- Histopathologically heterogeneous
- Typically contains fusions in NTRK1, NTRK2, NTRK3, ROS1, ALK or MET
- Distinct DNA methylation class
- Not yet graded; however, prognosis is more favorable than other pediatric type high grade gliomas
Terminology
- Not recommended
- Congenital glioblastoma
- Congenital anaplastic astrocytoma
- Congenital high grade glioma
- Infantile high grade glioma
- Pediatric glioblastoma
- Pediatric high grade glioma
ICD coding
- ICD-11: XH4ZM8 - infant type hemispheric glioma
Epidemiology
- Incidence data not yet available
- In a large cohort, M = F (Nat Commun 2019;10:4343)
- In the same large cohort, the median patient age was 2.8 months old (range: 0 - 12 months) (Nat Commun 2019;10:4343)
Sites
- Cerebral hemispheres (BMJ Case Rep 2016;2016:bcr2016217189, Genes Chromosomes Cancer 2016;55:677, Neuro Oncol 2015;17:1365, Pediatr Blood Cancer 2020;67:e28015, BMJ Case Rep 2019;12:e228248, Cancer Discov 2020;10:942, Nat Commun 2019;10:4343)
- Frequently superficial involvement that includes the leptomeninges (Cancer Discov 2020;10:942)
Pathophysiology
- Fusion genes containing an active tyrosine kinase domain from NTRK1, NTRK2, NTRK3, ALK, ROS1 or MET drive tumorigenesis via signaling through PI3K, MAPK or JAK pathways (Nat Commun 2019;10:4343, Cancer Discov 2020;10:942)
Etiology
- Unknown
Clinical features
- Typically acute presentation (BMJ Case Rep 2019;12:e228248, Front Oncol 2023;13:1123378)
- Head circumference may be large (Child Neurol Open 2022;9:2329048X221146982)
- Mass effect / midline shift (Child Neurol Open 2022;9:2329048X221146982, Front Oncol 2023;13:1123378)
- Nonspecific signs and symptoms ranging from agitation to lethargy (Pathologica 2022;114:422)
- Symptoms related to increased intracranial pressure, such as headache, nausea and vomiting (Ann Clin Transl Neurol 2023;10:836)
Diagnosis
- Identification of a cellular glioma located in the cerebral hemispheres and presenting in infancy
- Fusion in NTRK1, NTRK2, NTRK3, ROS1, MET, ALK or a DNA methylome profile aligned with infant type hemispheric glioma
Radiology description
- Large, hyperdense hemispheric lesions on computed tomography (CT) of the head, often with midline shift and hydrocephalus (BMJ Case Rep 2019;12:e228248, Cancer Genomics Proteomics 2022;19:711, Front Oncol 2023;13:1123378)
- Contrast enhancing, large tumors on magnetic resonance imaging (MRI) (Cancer Genomics Proteomics 2022;19:711, Child Neurol Open 2022;9:2329048X221146982, Front Oncol 2023;13:1123378, Ann Clin Transl Neurol 2023;10:836)
- Some studies describe severe mass effect, including subfalcine herniation (Child Neurol Open 2022;9:2329048X221146982, Front Oncol 2023;13:1123378)
Radiology images
Contributed by Jared T. Ahrendsen, M.D., Ph.D. and Nitin Wadhwani, M.D.
T1 postcontrast MRI
Prognostic factors
- Prognosis is more favorable than pediatric high grade gliomas
- In one study, median progression free survival was reported as 1.1 years (0.0 - 17.6) and median overall survival was reported as 1.9 years (0.0 - 17.7) (Nat Commun 2019;10:4343)
- Specifically, patients with ALK rearranged tumors seemed to have a better 5 year overall survival rate than patients with tumors with ROS1 alterations (53.8% versus 25%, respectively); patients with NTRK fusion positive tumors had an intermediate prognosis (5 year overall survival rate: 42.9%) (Nat Commun 2019;10:4343)
Case reports
- Full term infant boy born with a large left hemispheric mass and NTRK1 fusion (Child Neurol Open 2022;9:2329048X221146982)
- 3 month old girl with a large mass centered in the posterior left cerebral hemisphere and ATIC::ALK fusion (Front Oncol 2023;13:1123378)
- 3 month old girl with a right cerebral hemispheric mass and PPP1CB::ALK fusion (BMJ Case Rep 2019;12:e228248)
- 16 month old boy with a mass in the third ventricle and TPR::ROS1 fusion (Cancer Genomics Proteomics 2022;19:711)
- 3 year old boy with a large left parietooccipital mass, lung metastasis and QKI::ALK fusion (Ann Clin Transl Neurol 2023;10:836)
Treatment
- Complete resection that is safely possible
- RTK fusions can be therapeutically targeted
- Responses to specific inhibitors have been reported and may serve to complement conventional chemotherapy and radiotherapy (Cancer Discov 2020;10:942, Cancer Discov 2017;7:400, Br J Cancer 2018;119:693, Ann Clin Transl Neurol 2023;10:836, Front Oncol 2023;13:1123378)
Gross description
- Large, some with a cystic component and solid portion
- Hemorrhage or necrosis may occur (BMJ Case Rep 2016;2016:bcr2016217189, Genes Chromosomes Cancer 2016;55:677, Neuro Oncol 2015;17:1365, Pediatr Blood Cancer 2020;67:e28015, BMJ Case Rep 2019;12:e228248, Cancer Discov 2020;10:942, Nat Commun 2019;10:4343)
Frozen section description
- There are few published reports of intraoperative smears or frozen sections; they show astrocytic appearing tumor cells, with mitotic activity and other high grade histologic features (Surg Pathol Clin 2020;13:217, J Neurosurg Pediatr 2017;20:51, JCO Precis Oncol 2019;3:1)
Microscopic (histologic) description
- Tumor cells with astrocytic morphology that may include spindle cells and gemistocytes (Cancer Discov 2020;10:942)
- In general, tumor cells do not infiltrate adjacent brain parenchyma (Cancer Discov 2020;10:942)
- Some tumors may exhibit ependymal differentiation (Cancer Discov 2020;10:942, Neuro Oncol 2015;17:1365)
- Can have morphologic overlap with desmoplastic infantile ganglioglioma / astrocytoma (Childs Nerv Syst 2023;39:1861)
- High grade features such as palisading necrosis, mitotic activity and microvascular proliferation (Cancer Discov 2020;10:942)
- There can be low grade components or occasional ganglion cells (Cancer Discov 2020;10:942, Nat Commun 2019;10:4343, Pediatr Blood Cancer 2020;67:e28015, BMJ Case Rep 2019;12:e228248)
Microscopic (histologic) images
Contributed by Jared T. Ahrendsen, M.D., Ph.D. and Nitin Wadhwani, M.D.
Necrosis
Atypical glial cells
Mitotically active
GFAP positive
INI1 retained
Positive stains
- GFAP
- Olig2
- ALK (in tumors with ALK fusions) (Neuro Oncol 2015;17:1365, Nat Commun 2019;10:4343)
- Ki67 variable but usually elevated (Cancer Discov 2020;10:942, Brain Pathol 2023;33:e13182)
Negative stains
- IDH1 (R132H) (Cancer Discov 2020;10:942)
- H3F3A K27M (Cancer Discov 2020;10:942)
- H3F3A G34R / V (Cancer Discov 2020;10:942)
- BRAF V600E (Nat Commun 2019;10:4343)
Molecular / cytogenetics description
- Most contain genomic fusions involving NTRK1, NTRK2, NTRK3, ROS1, ALK or MET (Nat Commun 2019;10:4343, Cancer Discov 2020;10:942)
Sample pathology report
- Brain tumor, left frontal lobe, resection:
- Integrated diagnosis: infant type hemispheric glioma
- Histological diagnosis: high grade glioma
- Molecular information
- QK1::ALK fusion (by sequencing)
- ALK positive (immunohistochemistry; consistent with amplification)
- H3 G34R / V: negative (immunohistochemistry; consistent with wild type)
- H3 K27M: negative (immunohistochemistry; consistent with wild type)
- IDH: negative (R132H) immunohistochemistry; consistent with wild type)
Differential diagnosis
- Diffuse hemispheric glioma, H3 G34 mutant, CNS WHO grade 4:
- H3 G34R / V mutation
- Diffuse midline glioma, CNS WHO grade 4:
- H3 K27 alteration, midline location
- Desmoplastic infantile ganglioglioma / astrocytoma:
- Absence of necrosis and microvascular proliferation
- BRAF or RAF1 alterations
- Distinct DNA methylation class
- Supratentorial ependymoma, CNS WHO grade 2 or 3:
- ZFTA or YAP1 alterations
- Atypical teratoid / rhabdoid tumor, CNS WHO grade 4:
- Polyimmunophenotype
- Variable number of rhabdoid cells
- SMARCB1 or SMARCA4 alterations
- Diffuse low grade glioma, MAP kinase pathway altered:
- Low grade histologic features
- BRAF or FGFR1 alteration
Additional references
Board review style question #1
A 5 month old boy presents with feeding difficulties, poor head control and left hemiparesis that have progressed over the past few weeks. Head CT shows severe hydrocephalus and a large hyperdense lesion in the right cerebral hemisphere. A representative hematoxylin and eosin stained section of the resected tumor is shown (panel A). Tumor cells are GFAP positive (not shown) and there is high Ki67 expression (panel B). Next generation sequencing reveals a PPP1CB::ALK fusion without evidence of other genomic alterations. Strong cytoplasmic ALK expression is seen by immunohistochemistry (panel C), consistent with the presence of the PPP1CB::ALK fusion. What is your diagnosis?
- Diffuse hemispheric glioma, H3 G34 mutant, CNS WHO grade 4
- Diffuse low grade glioma, MAP kinase pathway altered
- Glioblastoma, IDH wild type, CNS WHO grade 4
- Infant type hemispheric glioma
Board review style answer #1
D. Infant type hemispheric glioma. This infant's hemispheric tumor shows high grade features, such as palisading necrosis. GFAP positivity in the tumor cells indicates the neoplasm is a glioma. The identification of an ALK receptor tyrosine kinase fusion confirms this neoplasm is an infant type hemispheric glioma. Answer B is incorrect because the pictured neoplasm shows high grade features, such as palisading necrosis. Answer C is incorrect because the diagnosis of glioblastoma is now reserved for adults with IDH wild type diffuse, high grade gliomas. Answer A is incorrect because a histone H3 G34R / V alteration was not identified in this infant's tumor.
Comment Here
Reference: Infant type hemispheric glioma
Comment Here
Reference: Infant type hemispheric glioma
