TY - JOUR
T1 - Intracranial myxoid mesenchymal tumors with EWSR1–CREB family gene fusions
T2 - myxoid variant of angiomatoid fibrous histiocytoma or novel entity?
AU - Bale, Tejus A.
AU - Oviedo, Angelica
AU - Kozakewich, Harry
AU - Giannini, Caterina
AU - Davineni, Phani K.
AU - Ligon, Keith
AU - Alexandrescu, Sanda
N1 - Funding Information:
This study could not have been possible without the financial and technical support provided by the Department of Pathology at Boston Children's Hospital, Histology Laboratory at Boston Children's Hospital, and by the technicians in the Center for Advanced Molecular Diagnosis at the Brigham and Women Hospital. The authors would also like to thank the following pathologists for their input and expertise during the clinical evaluation of these cases: Dr. J.L. Hornick (Brigham and Women's Hospital, Boston, MA), Dr. A. Bahrami (St. Jude's Children's Research Hospital, Memphis, TN), and Dr. Aimee Popp (WellStar Medical Group, Marietta, GA).
Publisher Copyright:
© 2017 International Society of Neuropathology
PY - 2018/3
Y1 - 2018/3
N2 - Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present three pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) were performed. A 12-year-old male (case 1), 14-year-old female (case 2), and 18-year-old male (case 3), presented with headaches, emesis, and seizures, respectively. The magnetic resonance images demonstrated tumors abutting the dura (cases 1 and 3) and in the third ventricle (case 2). All tumors were vascular, with solid sheets of monomorphic oval cells in a prominent myxoid/microcystic matrix. A thin fibrous pseudocapsule was present in all lesions, but definitive lymphocytic cuffing was absent. Morphologically, they closely resembled myxoid variant of angiomatoid fibrous histiocytoma. Mitoses were rare, and necrosis was absent. All tumors expressed desmin and GLUT1, and focal EMA and CD99. The proliferation index was low. FISH and NGS showed EWSR1–CREB1 fusion (cases 1 and 2), and EWSR1–CREM fusion (case 3). There were no FUS (16p11.2) or NR4A3 (9q22.33) rearrangements in case 3. Gains of 5q (including KCNIP1) and 11q (including CCND1) were present in cases 1 and 2. There were no common pathogenic genomic changes other than EWSR1 rearrangements across cases. CNS myxoid mesenchymal neoplasms with histological and immunophenotypic similarities to myxoid variant of AFH are rare, diagnostically challenging, and harbor EWSR1–CREB1 and also a novel EWSR1–CREM fusion not yet described in AFH. Therefore, it is uncertain if these tumors represent variants of AFH or a new entity. The copy number and mutational changes presented here provide support for future studies to further clarify this issue.
AB - Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present three pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) were performed. A 12-year-old male (case 1), 14-year-old female (case 2), and 18-year-old male (case 3), presented with headaches, emesis, and seizures, respectively. The magnetic resonance images demonstrated tumors abutting the dura (cases 1 and 3) and in the third ventricle (case 2). All tumors were vascular, with solid sheets of monomorphic oval cells in a prominent myxoid/microcystic matrix. A thin fibrous pseudocapsule was present in all lesions, but definitive lymphocytic cuffing was absent. Morphologically, they closely resembled myxoid variant of angiomatoid fibrous histiocytoma. Mitoses were rare, and necrosis was absent. All tumors expressed desmin and GLUT1, and focal EMA and CD99. The proliferation index was low. FISH and NGS showed EWSR1–CREB1 fusion (cases 1 and 2), and EWSR1–CREM fusion (case 3). There were no FUS (16p11.2) or NR4A3 (9q22.33) rearrangements in case 3. Gains of 5q (including KCNIP1) and 11q (including CCND1) were present in cases 1 and 2. There were no common pathogenic genomic changes other than EWSR1 rearrangements across cases. CNS myxoid mesenchymal neoplasms with histological and immunophenotypic similarities to myxoid variant of AFH are rare, diagnostically challenging, and harbor EWSR1–CREB1 and also a novel EWSR1–CREM fusion not yet described in AFH. Therefore, it is uncertain if these tumors represent variants of AFH or a new entity. The copy number and mutational changes presented here provide support for future studies to further clarify this issue.
KW - BRAF
KW - CREB1
KW - CREM
KW - EWSR1
KW - myxoid mesenchymal tumor
KW - myxoid variant angiomatoid fibrous histiocytoma
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85017443836&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017443836&partnerID=8YFLogxK
U2 - 10.1111/bpa.12504
DO - 10.1111/bpa.12504
M3 - Article
C2 - 28281318
AN - SCOPUS:85017443836
SN - 1015-6305
VL - 28
SP - 183
EP - 191
JO - Brain Pathology
JF - Brain Pathology
IS - 2
ER -