Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis

Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is no...

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Published inJournal of neuropathology and experimental neurology Vol. 77; no. 4; pp. 302 - 311
Main Authors Daoud, Elena V, Rajaram, Veena, Cai, Chunyu, Oberle, Robert J, Martin, Gregory R, Raisanen, Jack M, White, Charles L, Foong, Chan, Mickey, Bruce E, Pan, Edward, Hatanpaa, Kimmo J
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.04.2018
by American Association of Neuropathologists, Inc
Subjects
Adult
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Brain cancer
Brain Stem Neoplasms - diagnostic imaging
Brain Stem Neoplasms - genetics
Brain Stem Neoplasms - pathology
Brain tumors
Female
Follow-Up Studies
Genetic aspects
Glioma
Glioma - diagnostic imaging
Glioma - genetics
Glioma - pathology
Gliomas
Histones - genetics
Humans
Immunohistochemistry
Ki-67 Antigen - metabolism
Lysine - genetics
Magnetic Resonance Imaging
Male
Medical prognosis
Methionine - genetics
Middle Aged
Mutation
Mutation - genetics
Neurofilament Proteins - metabolism
Panobinostat
Pediatrics
Prognosis
Radiology
Retrospective Studies
Tumors
Glioma
Brainstem
Adult
Exophytic
H3K27M mutation
Midline
Survival
Online AccessGet full text
ISSN0022-3069
1554-6578
1554-6578
DOI10.1093/jnen/nly006

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Abstract Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
AbstractList Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic sub-classification of adult brainstem gliomas.
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic sub-classification of adult brainstem gliomas. Key Words: Adult, Brainstem, Exophytic, Glioma, H3K27M mutation, Midline, Survival.
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
Audience Academic
Author Martin, Gregory R
Oberle, Robert J
Daoud, Elena V
Hatanpaa, Kimmo J
Raisanen, Jack M
Cai, Chunyu
Pan, Edward
White, Charles L
Rajaram, Veena
Foong, Chan
Mickey, Bruce E
AuthorAffiliation Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Radiology, Central Texas Veterans Healthcare System, Temple, Texas Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas
AuthorAffiliation_xml – name: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Radiology, Central Texas Veterans Healthcare System, Temple, Texas Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas
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  surname: Daoud
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  organization: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Radiology, Central Texas Veterans Healthcare System, Temple, Texas Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas
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  surname: Cai
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29444279$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2018 American Association of Neuropathologists, Inc. All rights reserved. 2018
2018 by American Association of Neuropathologists, Inc.
COPYRIGHT 2018 Oxford University Press
Copyright © 2018 American Association of Neuropathologists
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Issue 4
Keywords Glioma
Brainstem
Adult
Exophytic
H3K27M mutation
Midline
Survival
Language English
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Snippet Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to...
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify...
Abstract Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to...
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SubjectTerms Adult
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Brain cancer
Brain Stem Neoplasms - diagnostic imaging
Brain Stem Neoplasms - genetics
Brain Stem Neoplasms - pathology
Brain tumors
Female
Follow-Up Studies
Genetic aspects
Glioma
Glioma - diagnostic imaging
Glioma - genetics
Glioma - pathology
Gliomas
Histones - genetics
Humans
Immunohistochemistry
Ki-67 Antigen - metabolism
Lysine - genetics
Magnetic Resonance Imaging
Male
Medical prognosis
Methionine - genetics
Middle Aged
Mutation
Mutation - genetics
Neurofilament Proteins - metabolism
Panobinostat
Pediatrics
Prognosis
Radiology
Retrospective Studies
Tumors
Title Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis
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