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| Home > Publications database > Histopathological patterns in atypical teratoid/rhabdoid tumors are related to molecular subgroup. |
| Home > Publications database > Histopathological patterns in atypical teratoid/rhabdoid tumors are related to molecular subgroup. |
| Journal Article | DKFZ-2021-01012 |
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2021
Wiley-Blackwell
Oxford
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Please use a persistent id in citations: doi:10.1111/bpa.12967
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.
Keyword(s): AT/RT ; DNA methylation profiling ; INI-1 ; cytokeratin ; histopathology
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