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@ARTICLE{Zin:168704,
author = {F. Zin and J. A. Cotter and C. Haberler and M. Dottermusch
and J. Neumann and U. Schüller and L. Schweizer and C.
Thomas and K. Nemes and P. D. Johann$^*$ and M. Kool$^*$ and
M. C. Frühwald and W. Paulus and A. Judkins and M.
Hasselblatt},
title = {{H}istopathological patterns in atypical teratoid/rhabdoid
tumors are related to molecular subgroup.},
journal = {Brain pathology},
volume = {31},
number = {5},
issn = {1750-3639},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2021-01012},
pages = {e12967},
year = {2021},
note = {2021 Sep;31(5):e12967},
abstract = {Atypical teratoid/rhabdoid tumor (AT/RT) is a highly
malignant tumor that may not only contain rhabdoid tumor
cells but also poorly differentiated small-round-blue cells
as well as areas with mesenchymal or epithelial
differentiation. Little is known on factors associated with
histopathological diversity. Recent studies demonstrated
three molecular subgroups of AT/RT, namely ATRT-TYR,
ATRT-SHH, and ATRT-MYC. We thus aimed to investigate if
morphological patterns might be related to molecular
subgroup status. Hematoxylin-eosin stained sections of 114
AT/RT with known molecular subgroup status were digitalized
and independently categorized by nine blinded observers into
four morphological categories, that is, 'rhabdoid,'
'small-round-blue,' 'epithelial,' and 'mesenchymal.' The
series comprised 48 ATRT-SHH, 40 ATRT-TYR, and 26 ATRT-MYC
tumors. Inter-observer agreement was moderate but
significant (Fleiss' kappa = 0.47; $95\%$ C.I. 0.41-0.53;
p < 0.001) and there was a highly significant overall
association between morphological categories and molecular
subgroups for each of the nine observers (p < 0.0001).
Specifically, the category 'epithelial' was found to be
over-represented in ATRT-TYR (p < 0.000001) and the
category 'small-round-blue' to be over-represented in
ATRT-SHH (p < 0.01). The majority of ATRT-MYC was
categorized as 'mesenchymal' or 'rhabdoid,' but this
association was less compelling. The specificity of the
category 'epithelial' for ATRT-TYR was highest and accounted
for $97\%$ (range: $88-99\%)$ whereas sensitivity was low
$[49\%$ (range: $35\%-63\%)].$ In line with these findings,
cytokeratin-positivity was highly overrepresented in
ATRT-TYR. In conclusion, morphological features of AT/RT
might reflect molecular alterations and may also provide a
first hint on molecular subgroup status, which will need to
be confirmed by DNA methylation profiling.},
keywords = {AT/RT (Other) / DNA methylation profiling (Other) / INI-1
(Other) / cytokeratin (Other) / histopathology (Other)},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33938067},
doi = {10.1111/bpa.12967},
url = {https://inrepo02.dkfz.de/record/168704},
}