Polymorphous low-grade neuroepithelial tumor of the young (PLNTY): an epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway.
Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population. Characteristic microscopic findings most notably include infiltrative growth, the invariable presence of oligodendroglioma-like cellular components, and intense immunolabeling for cluster of differentiation 34 (CD34). Moreover, integrative molecular profiling reveals a distinct DNA methylation signature for PLNTYs, along with frequent genetic abnormalities involving either B-Raf proto-oncogene (BRAF) or fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3). These findings suggest that PLNTY represents a distinct biological entity within the larger spectrum of pediatric, low-grade neuroepithelial tumors.
Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, 2130 W Holcombe Blvd, LSP9.4009, Houston, TX, 77030, USA. jhuse@mdanderson.org.
Jason T
0000-0003-4440-3250
JT
Huse
Department of Pathology, New York University Langone Medical Center, New York, NY, 10016, USA.
Matija
M
Snuderl
Division of Pediatric Neuro-oncology, German Cancer Research Center (DFKZ), 69120, Heidelberg, Germany.
David T W
DT
Jones
Department of Pathology, Nicklaus Children's Hospital, Miami, FL, 33155, USA.
Carole D
CD
Brathwaite
Department of Radiology, Nicklaus Children's Hospital, Miami, FL, 33155, USA.
Nolan
N
Altman
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, 10065, USA.
Ehud
E
Lavi
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
Richard
R
Saffery
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
Alexandra
A
Sexton-Oates
Institute of Neuropathology, University of Erlangen, 91054, Erlangen, Germany.
Ingmar
I
Blumcke
Department of Pathology, University of Heidelberg, 69120, Heidelberg, Germany.
David
D
Capper
Department of Pediatrics, New York University Langone Medical Center, New York, NY, 10016, USA.|Department of Ototlaryngology, New York University Langone Medical Center, New York, NY, 10016, USA.
Matthias A
MA
Karajannis
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 408 E 69th St. (Z564), New York, NY, 10065, USA.
Ryma
R
Benayed
Division of Pediatric Neuro-oncology, German Cancer Research Center (DFKZ), 69120, Heidelberg, Germany.
Lukas
L
Chavez
Department of Pathology, New York University Langone Medical Center, New York, NY, 10016, USA.
Cheddhi
C
Thomas
Department of Pathology, New York University Langone Medical Center, New York, NY, 10016, USA.
Jonathan
J
Serrano
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 408 E 69th St. (Z564), New York, NY, 10065, USA.
Laetitia
L
Borsu
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 408 E 69th St. (Z564), New York, NY, 10065, USA.
Marc
M
Ladanyi
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 408 E 69th St. (Z564), New York, NY, 10065, USA.
Marc K
MK
Rosenblum
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018302:Neoplasms, Neuroepithelial / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D009457:Neuroglia / Q000473:pathology; D009837:Oligodendroglioma / Q000235:genetics; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
D018952:Antigens, CD34; D005904:Glial Fibrillary Acidic Protein; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017468:Receptors, Fibroblast Growth Factor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases
BRAF; Epilepsy; FGFR2; FGFR3; Low-grade neuroepithelial tumor; Oligodendroglioma