Answer for BIR CoW 10 Apr 2022
K3 H27 mutant diffuse midline glioma
Findings
Evidence of illdefined T1 hypointense T2 heterointense lesion noted involving pons, extending in to right hemimidbrain, prepontine cisterns and right thalamus with expansion of pons seen and is seen encasing the right posterior cerebral artery with few areas of diffusion restriction On contrast administration , the lesion shows few areas of patchy enhancement
Discussion
Entity that represents the majority of diffuse intrinsic pontine gliomas, although identical tumors are also found elsewhere in the midline (e.g. brainstem, spinal cord and thalamus) . They are aggressive tumors with poor prognosis and are considered WHO grade 4 tumors regardless of histological features. The clinical presentation will clearly depend upon the location of the tumor. Typically patients with brainstem tumors present with multiple cranial nerve palsies, depending on the location of the tumor, and signs of raised intracranial pressure. Cerebellar signs may also be elicited including ataxia, dysarthria, nystagmus and sleep apnea. Diffuse midline glioma, H3 K27-altered was first added to the 2016 update of the WHO classification of CNS tumors and is now considered one of the pediatric-type diffuse high-grade gliomas.throughout the midline structures of the central nervous system including thalamus,brainstem,mesencephalic And most commonly pontine, others include medullary, spinal cord H3 K27M–mutant diffuse midline gliomas usually appear histologically as astrocytic tumors. In a minority of cases they appear histologically low-grade (without mitotic figures, microvascular proliferation or necrosis), however, even then they are considered WHO grade 4 tumors Immunophenotype S100: positive 3 NCAM1: positive OLIG2: positive H3F3A K27M mutation: usually positive, although other mutations are also recognized (see below) 3 p53 protein: positive in 50% 3 GFAP: variable chromogranin-A: negative NeuN: negative Recent genomic work has uncovered distinct mutations found in the majority of diffuse midline gliomas resulting in the inclusion of diffuse midline glioma H3 K27M–mutant as a distinct entity and the removal of diffuse intrinsic pontine gliomas from the current WHO classification of CNS tumors. These mutations are in the histone H3F3A gene (K27M mutations) or less frequently HIST1H3B and HIST2H3C genes . A number of other distinct but related histone gene mutations have also been identified in similar tumors . Recent genomic work has uncovered distinct mutations found in the majority of diffuse midline gliomas resulting in the inclusion of diffuse midline glioma H3 K27M–mutant as a distinct entity and the removal of diffuse intrinsic pontine gliomas from the current WHO classification of CNS tumors. These mutations are in the histone H3F3A gene (K27M mutations) or less frequently HIST1H3B and HIST2H3C genes . Radiographic features In tumors located within the pons, the pons is enlarged with the basilar artery displaced anteriorly against the clivus and potentially engulfed. The floor of the fourth ventricle is flattened ("flat floor of fourth ventricle sign") and obstructive hydrocephalus may be present. Occasionally the tumor is exophytic, either outwards into the basal cisterns or centrally in the 4th ventricle. Usually, the tumor is homogeneous pre-treatment, however, in a minority of patients areas of necrosis may be present. CT Typically hypodense with little, if any, enhancement. MRI T1: decreased intensity T2: heterogeneously increased T1 C+ (Gd): usually minimal (can enhance post-radiotherapy) DWI/ADC: usually normal, occasionally mildly restricted Extensive spread is relatively frequent, both craniocaudally to involve the cerebral hemispheres and spinal cord, as well as leptomeningeal spread
References
Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131 (6): 803-20. doi:10.1007/s00401-016-1545-1 - Pubmed citation 2. Castel D, Philippe C, Calmon R et-al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130 (6): 815-27. doi:10.1007/s00401-015-1478-0 - Free text at pubmed - Pubmed citation
Findings
Evidence of illdefined T1 hypointense T2 heterointense lesion noted involving pons, extending in to right hemimidbrain, prepontine cisterns and right thalamus with expansion of pons seen and is seen encasing the right posterior cerebral artery with few areas of diffusion restriction On contrast administration , the lesion shows few areas of patchy enhancement
Discussion
Entity that represents the majority of diffuse intrinsic pontine gliomas, although identical tumors are also found elsewhere in the midline (e.g. brainstem, spinal cord and thalamus) . They are aggressive tumors with poor prognosis and are considered WHO grade 4 tumors regardless of histological features. The clinical presentation will clearly depend upon the location of the tumor. Typically patients with brainstem tumors present with multiple cranial nerve palsies, depending on the location of the tumor, and signs of raised intracranial pressure. Cerebellar signs may also be elicited including ataxia, dysarthria, nystagmus and sleep apnea. Diffuse midline glioma, H3 K27-altered was first added to the 2016 update of the WHO classification of CNS tumors and is now considered one of the pediatric-type diffuse high-grade gliomas.throughout the midline structures of the central nervous system including thalamus,brainstem,mesencephalic And most commonly pontine, others include medullary, spinal cord H3 K27M–mutant diffuse midline gliomas usually appear histologically as astrocytic tumors. In a minority of cases they appear histologically low-grade (without mitotic figures, microvascular proliferation or necrosis), however, even then they are considered WHO grade 4 tumors Immunophenotype S100: positive 3 NCAM1: positive OLIG2: positive H3F3A K27M mutation: usually positive, although other mutations are also recognized (see below) 3 p53 protein: positive in 50% 3 GFAP: variable chromogranin-A: negative NeuN: negative Recent genomic work has uncovered distinct mutations found in the majority of diffuse midline gliomas resulting in the inclusion of diffuse midline glioma H3 K27M–mutant as a distinct entity and the removal of diffuse intrinsic pontine gliomas from the current WHO classification of CNS tumors. These mutations are in the histone H3F3A gene (K27M mutations) or less frequently HIST1H3B and HIST2H3C genes . A number of other distinct but related histone gene mutations have also been identified in similar tumors . Recent genomic work has uncovered distinct mutations found in the majority of diffuse midline gliomas resulting in the inclusion of diffuse midline glioma H3 K27M–mutant as a distinct entity and the removal of diffuse intrinsic pontine gliomas from the current WHO classification of CNS tumors. These mutations are in the histone H3F3A gene (K27M mutations) or less frequently HIST1H3B and HIST2H3C genes . Radiographic features In tumors located within the pons, the pons is enlarged with the basilar artery displaced anteriorly against the clivus and potentially engulfed. The floor of the fourth ventricle is flattened ("flat floor of fourth ventricle sign") and obstructive hydrocephalus may be present. Occasionally the tumor is exophytic, either outwards into the basal cisterns or centrally in the 4th ventricle. Usually, the tumor is homogeneous pre-treatment, however, in a minority of patients areas of necrosis may be present. CT Typically hypodense with little, if any, enhancement. MRI T1: decreased intensity T2: heterogeneously increased T1 C+ (Gd): usually minimal (can enhance post-radiotherapy) DWI/ADC: usually normal, occasionally mildly restricted Extensive spread is relatively frequent, both craniocaudally to involve the cerebral hemispheres and spinal cord, as well as leptomeningeal spread
References
Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131 (6): 803-20. doi:10.1007/s00401-016-1545-1 - Pubmed citation 2. Castel D, Philippe C, Calmon R et-al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130 (6): 815-27. doi:10.1007/s00401-015-1478-0 - Free text at pubmed - Pubmed citation
Note:
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!