Diffuse intrinsic pontine glioma: Difference between revisions
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==[[ Diffuse intrinsic pontine gliomaoverview|INTRODUCTION]]== | ==[[ Diffuse intrinsic pontine gliomaoverview|INTRODUCTION]]== | ||
The biologic nature of brainstem gliomas varies widely; these tumors might be low-grade and require minimal therapy, or they can be swiftly deadly even with vigorous therapy. The location of the tumor within the brainstem, the length of the clinical symptoms, and, increasingly, the mutational profile all affect the prognosis and course of treatment.<ref name="PMID:11723378.">{{cite journal |vauthors Guillamo JS|title= . Brain stem gliomas |PMID= 11723378|url=}}</ref> Histologically, these tumors are often glioblastomas (WHO grade 4) or astrocytomas (WHO grade 3; anaplastic). However, the prognosis is not better for individuals whose biopsy revealed WHO grade 2 malignancies.<ref name="PMID: 8817612.">{{cite journal |vauthors Epstein F|title= Practical decisions in the treatment of pediatric brain stem tumors |PMID= 8817612|url=}}</ref>High grade nonpontine gliomas, which are treated similarly to diffuse intrinsic pontine gliomas, make up around 10 to 20 percent of all nonpontine gliomas. | The biologic nature of brainstem gliomas varies widely; these tumors might be low-grade and require minimal therapy, or they can be swiftly deadly even with vigorous therapy. The location of the tumor within the brainstem, the length of the clinical symptoms, and, increasingly, the mutational profile all affect the prognosis and course of treatment.<ref name="PMID:11723378.">{{cite journal |vauthors Guillamo JS|title= . Brain stem gliomas |PMID= 11723378|url=}}</ref> Histologically, these tumors are often glioblastomas (WHO grade 4) or astrocytomas (WHO grade 3; anaplastic). However, the prognosis is not better for individuals whose biopsy revealed WHO grade 2 malignancies.<ref name="PMID: 8817612.">{{cite journal |vauthors Epstein F|title= Practical decisions in the treatment of pediatric brain stem tumors |PMID= 8817612|url=}}</ref>High grade nonpontine gliomas, which are treated similarly to diffuse intrinsic pontine gliomas, make up around 10 to 20 percent of all nonpontine gliomas. | ||
==[[ Diffuse intrinsic pontine gliomahistorical perspective|EPIDEMIOLOGY]]== | ==[[ Diffuse intrinsic pontine gliomahistorical perspective|EPIDEMIOLOGY]]== | ||
About one-third of all pediatric high-grade gliomas and 10 to 20 percent of all pediatric central nervous system cancers are brainstem (midbrain, pons, and medulla oblongata) gliomas. Compared to adults, children are more likely to have brainstem gliomas. For instance, about 300 pediatric cases and 100 adult cases are recorded annually in the United States. Five to nine years old is the median age for diagnosis in children, with a slight female sex preponderance.<ref name="PMID:33346835.">{{cite journal |vauthors Patil N|title= Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States, 2000-2017. |PMID= 33346835|url=}}</ref> | About one-third of all pediatric high-grade gliomas and 10 to 20 percent of all pediatric central nervous system cancers are brainstem (midbrain, pons, and medulla oblongata) gliomas. Compared to adults, children are more likely to have brainstem gliomas. For instance, about 300 pediatric cases and 100 adult cases are recorded annually in the United States. Five to nine years old is the median age for diagnosis in children, with a slight female sex preponderance.<ref name="PMID:33346835.">{{cite journal |vauthors Patil N|title= Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States, 2000-2017. |PMID= 33346835|url=}}</ref> | ||
==[[ Diffuse intrinsic pontine gliomapathophysiology|Pathophysiology]]== | ==[[ Diffuse intrinsic pontine gliomapathophysiology|Pathophysiology]]== | ||
Diffuse intrinsic pontine gliomas are almost always high-grade astrocytomas when biopsied, while up to 25% may show low grade on traditional histologic characteristics. The majority of the tumors also develop quickly. Significantly, in diffuse intrinsic pontine gliomas, histopathologic grade is not correlated with prognosis; in fact, even low-grade diffuse pontine lesions behave aggressively and have a prognosis that is comparable to that of high-grade tumors.Seldom have pons glial tumors spread to distant locations at the time of diagnosis. Rather, they usually go down well-established fiber networks, particularly into the cerebellum and thalamus. Although spinal seeding is uncommon, it might be seen as the illness progresses.<ref name="PMID: 16983574..">{{cite journal |vauthors Singh S|title= Leptomeninges as a site of relapse in locally controlled, diffuse pontine glioma with review of literature, 2000-2017. |PMID= 16983574.|url=}}</ref> | Diffuse intrinsic pontine gliomas are almost always high-grade astrocytomas when biopsied, while up to 25% may show low grade on traditional histologic characteristics. The majority of the tumors also develop quickly. Significantly, in diffuse intrinsic pontine gliomas, histopathologic grade is not correlated with prognosis; in fact, even low-grade diffuse pontine lesions behave aggressively and have a prognosis that is comparable to that of high-grade tumors.Seldom have pons glial tumors spread to distant locations at the time of diagnosis. Rather, they usually go down well-established fiber networks, particularly into the cerebellum and thalamus. Although spinal seeding is uncommon, it might be seen as the illness progresses.<ref name="PMID: 16983574..">{{cite journal |vauthors Singh S|title= Leptomeninges as a site of relapse in locally controlled, diffuse pontine glioma with review of literature, 2000-2017. |PMID= 16983574.|url=}}</ref> | ||
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3.Pediatric diffuse intrinsic pontine gliomas are exceedingly unusual to have mutations in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2), which characterizes a significant fraction of adult grade 2 and 3 diffuse gliomas.<ref name="PMID:26297251.">{{cite journal |vauthors Feng J|title= The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults. 2000-2017. |PMID=26297251|url=}}</ref> On the other hand, up to 25% of adult brainstem gliomas may have IDH1/2 mutations, the majority of which are non-R132H variations. These mutations are linked to a better prognosis and may benefit from adjuvant chemotherapy in addition to radiation therapy. | 3.Pediatric diffuse intrinsic pontine gliomas are exceedingly unusual to have mutations in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2), which characterizes a significant fraction of adult grade 2 and 3 diffuse gliomas.<ref name="PMID:26297251.">{{cite journal |vauthors Feng J|title= The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults. 2000-2017. |PMID=26297251|url=}}</ref> On the other hand, up to 25% of adult brainstem gliomas may have IDH1/2 mutations, the majority of which are non-R132H variations. These mutations are linked to a better prognosis and may benefit from adjuvant chemotherapy in addition to radiation therapy. | ||
==[[ Diffuse intrinsic pontine gliomacauses| | ==[[ Diffuse intrinsic pontine gliomacauses|CLINICAL FEATURES]]== | ||
Depending on the location of tumour the clinical features change accordingly.There are very few pathognomonic features pertaining to there syndrome . | |||
-In more than 50% of cases, there are ataxia, cranial nerve palsies, and long tract symptoms including hemiparesis. Although III, IV, IX, and X may also be impacted, cranial nerves VI and VII are most frequently afflicted. | |||
-Less than 10% of patients had hydrocephalus with high intracranial pressure (ICP) upon presentation. | |||
-While little punctate hemorrhages might be observed in a large number of instances, significant intratumoral hemorrhage can be present in around 6% of patients at the time of diagnosis. | |||
Usually manifesting within three months, diffuse intrinsic pontine gliomas have longer-lasting symptoms than focal brainstem gliomas. For brainstem tumors, the length of symptoms in relation to traditional radiography findings is a significant prognostic factor. Individuals who have had their symptoms for more than six months at the time of diagnosis often do considerably better than those who have had them for less time. | |||
==[[ Diffuse intrinsic pontine glioma|Diagnosis]]== | |||
IMAGING | |||
Imaging tests are the gold standard for brainstem tumor identification and classification. MRIs and, less commonly, computed tomography (CT) are the most commonly used imaging techniques.Diffuse intrinsic pontine gliomas have a typical appearance on CT scans with hypodense to isodense appearance and variable contrast enhancement. Calcium is rarely identified within the tumor. MRI is superior to CT for defining these lesions. On MRI, diffuse pontine lesions are expansile, typically hypointense on T1- and hyperintense on T2-weighted images | |||
High-grade tumors usually spread to nearby regions, such as the midbrain or medulla. Typically, axial development is seen through the cerebellar peduncles and into the cerebellum; malignancies enlarge the pons rather than moving it. They often surround the basilar artery and include exophytic components into the prepontine cistern. The tumors seem to respect the pontomedullary border on sagittal imaging. | |||
The tumors' internal contrast enhancement might vary, sometimes ring-enhancing with centrally located necrosis. When ring-enhancing lesions seem well-circumscribed on MRI, this does not always mean the lesion is lower grade or has a more benign clinical history; this is sometimes not verified at the time of surgery or autopsy. There is hardly any contrast enhancement for diffuse pontine lesions. Diffuse uniform enhancement tumors are generally linked with longer symptoms, are more likely to be low grade tumors, and may present with a better prognosis.While MRI has become the standard method of evaluation of diffuse intrinsic pontine gliomas, the heterogeneous signal characteristics of these lesions and interobserver variability make serial assessment difficult<ref name="PMID:18587536.">{{cite journal |vauthors Hayward RM|title= Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas.. 2000-2017. |PMID=18587536|url=}}</ref> | |||
==[[ Diffuse intrinsic pontine | ==[[ Diffuse intrinsic pontine glioma|Differential Diagnosis]]== | ||
The most prevalent causes of nonneoplastic lesions in the brainstem include vascular malformations, encephalitis, uncommon parasite cysts, demyelinating illnesses (e.g., multiple sclerosis), and hamartomas in individuals with neurofibromatosis. There have also been isolated reports of adult extracranial carcinoma metastases in the pons. | |||
==[[ Diffuse intrinsic pontine | ==[[ Diffuse intrinsic pontine glioma|Treatment]]== | ||
Treatment for a patient with a diffuse intrinsic pontine glioma consists of targeted tumor-specific interventions (chemotherapy, radiation treatment, and surgery) in addition to managing peritumoral edema. It is recommended that individuals take part in clinical trials, especially as the molecular pathophysiology of these cancers becomes clearer and targeted medicines start to be tested in humans. | |||
Revision as of 08:45, 12 July 2024
Template:Diffuse intrinsic pontine glioma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Rithish Nimmagadda,MBBS.[2]
INTRODUCTION
The biologic nature of brainstem gliomas varies widely; these tumors might be low-grade and require minimal therapy, or they can be swiftly deadly even with vigorous therapy. The location of the tumor within the brainstem, the length of the clinical symptoms, and, increasingly, the mutational profile all affect the prognosis and course of treatment.[1] Histologically, these tumors are often glioblastomas (WHO grade 4) or astrocytomas (WHO grade 3; anaplastic). However, the prognosis is not better for individuals whose biopsy revealed WHO grade 2 malignancies.[2]High grade nonpontine gliomas, which are treated similarly to diffuse intrinsic pontine gliomas, make up around 10 to 20 percent of all nonpontine gliomas.
EPIDEMIOLOGY
About one-third of all pediatric high-grade gliomas and 10 to 20 percent of all pediatric central nervous system cancers are brainstem (midbrain, pons, and medulla oblongata) gliomas. Compared to adults, children are more likely to have brainstem gliomas. For instance, about 300 pediatric cases and 100 adult cases are recorded annually in the United States. Five to nine years old is the median age for diagnosis in children, with a slight female sex preponderance.[3]
Pathophysiology
Diffuse intrinsic pontine gliomas are almost always high-grade astrocytomas when biopsied, while up to 25% may show low grade on traditional histologic characteristics. The majority of the tumors also develop quickly. Significantly, in diffuse intrinsic pontine gliomas, histopathologic grade is not correlated with prognosis; in fact, even low-grade diffuse pontine lesions behave aggressively and have a prognosis that is comparable to that of high-grade tumors.Seldom have pons glial tumors spread to distant locations at the time of diagnosis. Rather, they usually go down well-established fiber networks, particularly into the cerebellum and thalamus. Although spinal seeding is uncommon, it might be seen as the illness progresses.[4]
MOLECULAR LEVEL-
1.Nearly 80 percent of diffuse intrinsic pontine gliomas contain mutually exclusive mutations in either HIST3H1B, one of many genes encoding histone H3.1, or H3F3A, one of two genes expressing the histone H3.3 variation. These mutations appear to be present in all tumor cells. Both mutations change the binding of mutant histone H3 to polycomb repressive complex 2 (PRC2), a crucial developmental regulator of gene expression, by substituting methionine for lysine 27 (H3 K27M).[5]
2.Platelet-derived growth factor receptor (PDGFR) A and c-Met protein overexpression and amplification appear to be key molecular steps in the transition of cells to a malignant phenotype, more frequently observed in tumors with the H3.3 mutation. About 15% of diffuse intrinsic pontine gliomas have activating mutations in phosphatidylinositol 3-kinase (PI3K). [6]
3.Pediatric diffuse intrinsic pontine gliomas are exceedingly unusual to have mutations in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2), which characterizes a significant fraction of adult grade 2 and 3 diffuse gliomas.[7] On the other hand, up to 25% of adult brainstem gliomas may have IDH1/2 mutations, the majority of which are non-R132H variations. These mutations are linked to a better prognosis and may benefit from adjuvant chemotherapy in addition to radiation therapy.
CLINICAL FEATURES
Depending on the location of tumour the clinical features change accordingly.There are very few pathognomonic features pertaining to there syndrome .
-In more than 50% of cases, there are ataxia, cranial nerve palsies, and long tract symptoms including hemiparesis. Although III, IV, IX, and X may also be impacted, cranial nerves VI and VII are most frequently afflicted.
-Less than 10% of patients had hydrocephalus with high intracranial pressure (ICP) upon presentation.
-While little punctate hemorrhages might be observed in a large number of instances, significant intratumoral hemorrhage can be present in around 6% of patients at the time of diagnosis.
Usually manifesting within three months, diffuse intrinsic pontine gliomas have longer-lasting symptoms than focal brainstem gliomas. For brainstem tumors, the length of symptoms in relation to traditional radiography findings is a significant prognostic factor. Individuals who have had their symptoms for more than six months at the time of diagnosis often do considerably better than those who have had them for less time.
Diagnosis
IMAGING
Imaging tests are the gold standard for brainstem tumor identification and classification. MRIs and, less commonly, computed tomography (CT) are the most commonly used imaging techniques.Diffuse intrinsic pontine gliomas have a typical appearance on CT scans with hypodense to isodense appearance and variable contrast enhancement. Calcium is rarely identified within the tumor. MRI is superior to CT for defining these lesions. On MRI, diffuse pontine lesions are expansile, typically hypointense on T1- and hyperintense on T2-weighted images
High-grade tumors usually spread to nearby regions, such as the midbrain or medulla. Typically, axial development is seen through the cerebellar peduncles and into the cerebellum; malignancies enlarge the pons rather than moving it. They often surround the basilar artery and include exophytic components into the prepontine cistern. The tumors seem to respect the pontomedullary border on sagittal imaging.
The tumors' internal contrast enhancement might vary, sometimes ring-enhancing with centrally located necrosis. When ring-enhancing lesions seem well-circumscribed on MRI, this does not always mean the lesion is lower grade or has a more benign clinical history; this is sometimes not verified at the time of surgery or autopsy. There is hardly any contrast enhancement for diffuse pontine lesions. Diffuse uniform enhancement tumors are generally linked with longer symptoms, are more likely to be low grade tumors, and may present with a better prognosis.While MRI has become the standard method of evaluation of diffuse intrinsic pontine gliomas, the heterogeneous signal characteristics of these lesions and interobserver variability make serial assessment difficult[8]
Differential Diagnosis
The most prevalent causes of nonneoplastic lesions in the brainstem include vascular malformations, encephalitis, uncommon parasite cysts, demyelinating illnesses (e.g., multiple sclerosis), and hamartomas in individuals with neurofibromatosis. There have also been isolated reports of adult extracranial carcinoma metastases in the pons.
Treatment
Treatment for a patient with a diffuse intrinsic pontine glioma consists of targeted tumor-specific interventions (chemotherapy, radiation treatment, and surgery) in addition to managing peritumoral edema. It is recommended that individuals take part in clinical trials, especially as the molecular pathophysiology of these cancers becomes clearer and targeted medicines start to be tested in humans.
- ↑ ". Brain stem gliomas". PMID 11723378. Text "vauthors Guillamo JS" ignored (help)
- ↑ "Practical decisions in the treatment of pediatric brain stem tumors". PMID 8817612. Text "vauthors Epstein F" ignored (help)
- ↑ "Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States, 2000-2017". PMID 33346835 Check
|pmid=value (help). Text "vauthors Patil N" ignored (help) - ↑ "Leptomeninges as a site of relapse in locally controlled, diffuse pontine glioma with review of literature, 2000-2017". PMID 16983574. Check
|pmid=value (help). Text "vauthors Singh S" ignored (help) - ↑ "Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics., 2000-2017". PMID 26727948. Text "vauthors Hoffman LM" ignored (help)
- ↑ "SMesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. 2000-2017". PMID 22389665. Text "vauthors Puget S" ignored (help)
- ↑ "The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults. 2000-2017". PMID 26297251. Text "vauthors Feng J" ignored (help)
- ↑ "Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas.. 2000-2017". PMID 18587536. Text "vauthors Hayward RM" ignored (help)