Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients ...Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients may benefit from irradiation particularly in the setting of inoperability,incomplete resection,or recurrent disease.While conventionally fractionated radiation therapy has been traditionally utilized for radiotherapeutic management,stereotactic irradiation strategies have been introduced more recently to improve the toxicity profile of radiation delivery without compromising tumor control.PAs may be suitable for radiosurgical management due to their typical appearance as well circumscribed lesions.Focused and precise targeting of these well-defined lesions under stereotactic immobilization and image guidance may offer great potential for achieving an improved therapeutic ratio by virtue of radiosurgical techniques.Given the high conformality along with steep dose gradients around the target volume allowing for reduced normal tissue exposure,radiosurgery may be considered a viable modality of radiotherapeutic management.Another advantage of radiosurgery may be the completion of therapy in a usually shorter overall treatment time,which may be particularly well suited for children with requirement of anesthesia during irradiation.Several studies have addressed the utility of radiosurgery particularly as an adjuvant or salvage treatment modality for PA.Nevertheless,despite the growing body of evidence supporting the use of radiosurgery,there is need for a high level of evidence to dictate treatment decisions and establish its optimal role in the management of PA.Herein,we provide a concise review of radiosurgery for PA in light of the literature.展开更多
Objective To analyze and summarize MRI findings of brain pilocytic astrocytoma in adults.Methods Thirtytwo cases(13 males and 19 females)of brain pilocytic astrocytoma in adults confirmed by surgery and pathology were...Objective To analyze and summarize MRI findings of brain pilocytic astrocytoma in adults.Methods Thirtytwo cases(13 males and 19 females)of brain pilocytic astrocytoma in adults confirmed by surgery and pathology were reviewed and studied including MRI manifestation and pathologic data.The ages of the patients ranged展开更多
Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in th...Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum.MRI scanning showed a tumor involved the cerebellar vermis,tonsil,the forth ventricle and brainstem.It was homogeneous isointensity on T1WI,relative hyper-intensity on T2WI,hyper-intensity on fluid attenuated inversion recovery （FLAIR） images,and uniform enhancement on contrast T1WI.The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma.Follow-up at the 5th month,MRI showed the residual tumor enlarged at the brainstem.The patient survived 10 months after the operation,and finally died of respiration failure resulting from brainstem dysfunction.展开更多
Objective： The aim of this study was to study the clinicopathological and immunohistochemical features of pilo- myxoid astrocytoma （PMA）. Methods： The clinical and pathologic features in six cases of PMA were anal...Objective： The aim of this study was to study the clinicopathological and immunohistochemical features of pilo- myxoid astrocytoma （PMA）. Methods： The clinical and pathologic features in six cases of PMA were analyzed. Immunohisto- chemical staining for glial fibrillary acidic protein （GFAP）, synaptophysin （Syn）, Chromogranin A （CgA）, cytokeratin （AEI/AE3）, epithelial membrane antigen （EMA） and Ki67 was performed on paraffin-embedded sections. Results： Among the six cases, five occurred in female patients, one was male, the age at diagnosis ranged from 2 to 15 years. Four cases were located in the hypothalamic area and optic pathway, one case in the third ventricle, and one case in left parietal lobe. On imaging, PMAs often appears as well-circumscribed mass. Microscopically, the tumor was composed of monomorphous bipolar （piloid） cells setting in a prominent myxoid background with an angiocentric radiating growth pattern in some areas. PMA lacked biphasic pattern, Rosenthal fibers and eosinophilic granular bodies which were usually typical in a classic pilocytic astrocytoma （PA）. Immunohistochemcal study showed that the tumor cells were diffusely positive for GFAP. Syn positive staining was observed in one case. The Ki67 labeling index measured less than 5%. Conclusion： PMA is a distinct aggressive variant of pilocytic astrocytoma with special histological and immunohistochemical features. It is typically a rare tumor of early childhood. Im- munohistochemical staining for GFAP and Syn is helpful in differential diagnosis.展开更多
Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied wi...Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.展开更多
文摘Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients may benefit from irradiation particularly in the setting of inoperability,incomplete resection,or recurrent disease.While conventionally fractionated radiation therapy has been traditionally utilized for radiotherapeutic management,stereotactic irradiation strategies have been introduced more recently to improve the toxicity profile of radiation delivery without compromising tumor control.PAs may be suitable for radiosurgical management due to their typical appearance as well circumscribed lesions.Focused and precise targeting of these well-defined lesions under stereotactic immobilization and image guidance may offer great potential for achieving an improved therapeutic ratio by virtue of radiosurgical techniques.Given the high conformality along with steep dose gradients around the target volume allowing for reduced normal tissue exposure,radiosurgery may be considered a viable modality of radiotherapeutic management.Another advantage of radiosurgery may be the completion of therapy in a usually shorter overall treatment time,which may be particularly well suited for children with requirement of anesthesia during irradiation.Several studies have addressed the utility of radiosurgery particularly as an adjuvant or salvage treatment modality for PA.Nevertheless,despite the growing body of evidence supporting the use of radiosurgery,there is need for a high level of evidence to dictate treatment decisions and establish its optimal role in the management of PA.Herein,we provide a concise review of radiosurgery for PA in light of the literature.
文摘Objective To analyze and summarize MRI findings of brain pilocytic astrocytoma in adults.Methods Thirtytwo cases(13 males and 19 females)of brain pilocytic astrocytoma in adults confirmed by surgery and pathology were reviewed and studied including MRI manifestation and pathologic data.The ages of the patients ranged
文摘Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum.MRI scanning showed a tumor involved the cerebellar vermis,tonsil,the forth ventricle and brainstem.It was homogeneous isointensity on T1WI,relative hyper-intensity on T2WI,hyper-intensity on fluid attenuated inversion recovery （FLAIR） images,and uniform enhancement on contrast T1WI.The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma.Follow-up at the 5th month,MRI showed the residual tumor enlarged at the brainstem.The patient survived 10 months after the operation,and finally died of respiration failure resulting from brainstem dysfunction.
文摘Objective： The aim of this study was to study the clinicopathological and immunohistochemical features of pilo- myxoid astrocytoma （PMA）. Methods： The clinical and pathologic features in six cases of PMA were analyzed. Immunohisto- chemical staining for glial fibrillary acidic protein （GFAP）, synaptophysin （Syn）, Chromogranin A （CgA）, cytokeratin （AEI/AE3）, epithelial membrane antigen （EMA） and Ki67 was performed on paraffin-embedded sections. Results： Among the six cases, five occurred in female patients, one was male, the age at diagnosis ranged from 2 to 15 years. Four cases were located in the hypothalamic area and optic pathway, one case in the third ventricle, and one case in left parietal lobe. On imaging, PMAs often appears as well-circumscribed mass. Microscopically, the tumor was composed of monomorphous bipolar （piloid） cells setting in a prominent myxoid background with an angiocentric radiating growth pattern in some areas. PMA lacked biphasic pattern, Rosenthal fibers and eosinophilic granular bodies which were usually typical in a classic pilocytic astrocytoma （PA）. Immunohistochemcal study showed that the tumor cells were diffusely positive for GFAP. Syn positive staining was observed in one case. The Ki67 labeling index measured less than 5%. Conclusion： PMA is a distinct aggressive variant of pilocytic astrocytoma with special histological and immunohistochemical features. It is typically a rare tumor of early childhood. Im- munohistochemical staining for GFAP and Syn is helpful in differential diagnosis.
基金supported by The Brain Tumour Charity(grant number GN-000707)supported by DKTK JF Upgrade Next Gen LOGGIC(B310-JF-LOGGIC-MDE)supported by the DFG through a Heisenberg professorship(BR 3662/5-1)and SFB-1479 Oncoescape-Project ID:441891347(P14)。
文摘Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.
