PMID- 25047029
OWN - NLM
STAT- MEDLINE
DCOM- 20150515
LR  - 20220317
IS  - 1432-0533 (Electronic)
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 128
IP  - 4
DP  - 2014 Oct
TI  - Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: 
      diagnostic and therapeutic implications.
PG  - 573-81
LID - 10.1007/s00401-014-1319-6 [doi]
AB  - Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related 
      death in children. In the majority of cases diagnosis is based on clinical and 
      MRI findings, resulting in the scarcity of pre-treatment specimens available to 
      study. Our group has developed an autopsy-based protocol to investigate the 
      histologic and biologic spectrum of DIPG. This has also allowed us to investigate 
      the terminal pattern of disease and gain a better understanding of what 
      challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with 
      well documented clinical history and molecular data and describe the pathological 
      features of this disease in relation to clinical and genetic features. 
      Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were 
      pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients 
      had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 
      had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal 
      tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade 
      II-IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT 
      phenotype were only found in WHO grade III-IV astrocytomas, while PIK3CA 
      mutations and PDGFRA gains/amplifications were found in WHO grade II-IV 
      astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of 
      their tumour. Further, diffuse invasion of the brainstem, spinal cord and 
      thalamus was common with some cases showing spread as distant as the frontal 
      lobes. These findings suggest that focal radiation may be inadequate for some of 
      these patients. Importantly, we show that clinically classic DIPGs represent a 
      diverse histologic spectrum, including multiple cases which would fit WHO 
      criteria of grade II astrocytoma which nevertheless behave clinically as 
      high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests 
      that the current WHO astrocytoma grading scheme may not appropriately predict 
      outcome for paediatric brainstem gliomas.
FAU - Buczkowicz, Pawel
AU  - Buczkowicz P
AD  - Division of Pathology, The Hospital for Sick Children, 555 University Avenue, 
      Toronto, ON, M5G 1X8, Canada.
FAU - Bartels, Ute
AU  - Bartels U
FAU - Bouffet, Eric
AU  - Bouffet E
FAU - Becher, Oren
AU  - Becher O
FAU - Hawkins, Cynthia
AU  - Hawkins C
LA  - eng
GR  - MOP 115004/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140722
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Histones)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adolescent
MH  - Autopsy
MH  - Brain Stem Neoplasms/*genetics/mortality/*pathology
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Female
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Glioma/*genetics/mortality/*pathology
MH  - Histones/*genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mutation/*genetics
MH  - Neuroectodermal Tumors, Primitive/genetics/pathology
MH  - Proportional Hazards Models
MH  - Tumor Suppressor Protein p53/genetics
PMC - PMC4159563
EDAT- 2014/07/23 06:00
MHDA- 2015/05/16 06:00
PMCR- 2014/07/22
CRDT- 2014/07/23 06:00
PHST- 2014/03/17 00:00 [received]
PHST- 2014/06/28 00:00 [accepted]
PHST- 2014/06/24 00:00 [revised]
PHST- 2014/07/23 06:00 [entrez]
PHST- 2014/07/23 06:00 [pubmed]
PHST- 2015/05/16 06:00 [medline]
PHST- 2014/07/22 00:00 [pmc-release]
AID - 1319 [pii]
AID - 10.1007/s00401-014-1319-6 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2014 Oct;128(4):573-81. doi: 10.1007/s00401-014-1319-6. Epub 
      2014 Jul 22.