Norman L Lehman1, Eyas M Hattab2, Bret C Mobley2, Aisulu Usubalieva2, Matthew J Schniederjan2, Roger E McLendon2, Werner Paulus2, Elisabeth J Rushing2, Maria-Magdalena Georgescu2, Marta Couce2, Mohanpal S Dulai2, Mark L Cohen2, Christopher R Pierson2, Jack M Raisanen2, Sarah E Martin2, Trang D Lehman2, Eric S Lipp2, Jose M Bonnin2, Mousa A Al-Abbadi2, Kara Kenworthy2, Kevin Zhao2, Nehad Mohamed2, Guojuan Zhang2, Weiqiang Zhao2. 1. Department of Pathology, The Ohio State University, Columbus, Ohio (N.L.L., A.U., C.R.P., K.K., K.Z., N.M., G.Z., W.Z.); Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana (E.M.H., J.M.B.); Department of Pathology, Vanderbilt University, Nashville, Tennessee (B.C.M.); Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia (M.J.S.); Department of Pathology, Duke University, Durham, North Carolina (R.E.M., E.S.L.); Institute of Neuropathology, University Hospital Münster, Germany (W.P.); Institute for Neuropathology, University Hospital of Zurich, Switzerland (E.J.R.); Department of Pathology, The University of Texas Southwestern, Dallas, Texas (M.-M.G., J.M.R.); Department of Pathology, Case Western Reserve University, Cleveland, Ohio (M.C., M.L.C.); Department of Anatomic Pathology, Beaumont Hospital, Royal Oak, Michigan (M.S.D.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio (C.R.P.); Department of Pathology, University of Illinois, Peoria, Illinois (S.E.M.); Department of Pathology, Sheikh Khalifa Medical City, Abu Dhabi, UAE (M.A.A.-A.); Department of Family and Community Medicine, Contra Costa Regional Medical Center, Martinez, California (T.D.L.) nllehman@yahoo.com. 2. Department of Pathology, The Ohio State University, Columbus, Ohio (N.L.L., A.U., C.R.P., K.K., K.Z., N.M., G.Z., W.Z.); Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana (E.M.H., J.M.B.); Department of Pathology, Vanderbilt University, Nashville, Tennessee (B.C.M.); Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia (M.J.S.); Department of Pathology, Duke University, Durham, North Carolina (R.E.M., E.S.L.); Institute of Neuropathology, University Hospital Münster, Germany (W.P.); Institute for Neuropathology, University Hospital of Zurich, Switzerland (E.J.R.); Department of Pathology, The University of Texas Southwestern, Dallas, Texas (M.-M.G., J.M.R.); Department of Pathology, Case Western Reserve University, Cleveland, Ohio (M.C., M.L.C.); Department of Anatomic Pathology, Beaumont Hospital, Royal Oak, Michigan (M.S.D.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio (C.R.P.); Department of Pathology, University of Illinois, Peoria, Illinois (S.E.M.); Department of Pathology, Sheikh Khalifa Medical City, Abu Dhabi, UAE (M.A.A.-A.); Department of Family and Community Medicine, Contra Costa Regional Medical Center, Martinez, California (T.D.L.).
Abstract
BACKGROUND: Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. RESULTS: Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. CONCLUSIONS: In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.
BACKGROUND:Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. RESULTS: Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. CONCLUSIONS: In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.
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