Lack of reproducibility of histopathological features in MYC‐rearranged large B cell lymphoma using digital whole slide images: a study from the Lunenburg lymphoma biomarker consortium

Aims Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high‐grade B cell lymphoma (HGBL) are difficult to apply in practice....

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Veröffentlicht in:Histopathology Jg. 82; H. 7; S. 1105 - 1111
Hauptverfasser: Natkunam, Yasodha, Jong, Daphne, Farinha, Pedro, Gaulard, Philippe, Klapper, Wolfram, Rosenwald, Andreas, Sander, Birgitta, Tooze, Reuben, Advani, Ranjana, Burton, Catherine, Gribben, John G, Kersten, Marie‐José, Kimby, Eva, Lenz, Georg, Molina, Thierry, Morschhauser, Franck, Scott, David, Sehn, Laurie, Stevens, Wendy, Clear, Andrew, Baia, Maryse, Habi, Abdelmalek, Elsensohn, Mad‐Helenie, Langlois‐Jacques, Carole, Maucort‐Boulch, Delphine, Calaminici, Maria
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Wiley Subscription Services, Inc 01.06.2023
Schlagworte:
B-cell lymphoma
Biomarkers
Cell size
diffuse large B cell lymphoma
digital whole slide image
Discordance
FISH
Fluorescence in situ hybridization
Gene Rearrangement
Growth patterns
high‐grade B cell lymphoma
Humans
Lymphoma
Lymphoma, Large B-Cell, Diffuse - diagnosis
Lymphoma, Large B-Cell, Diffuse - genetics
Lymphoma, Large B-Cell, Diffuse - pathology
Myc protein
MYC‐rearrangement
Nucleoli
Pleomorphism
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-6 - genetics
Proto-Oncogene Proteins c-myc - genetics
Reproducibility
Reproducibility of Results
digital whole slide image
high-grade B cell lymphoma
FISH
MYC-rearrangement
diffuse large B cell lymphoma
ISSN:0309-0167, 1365-2559, 1365-2559
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Zusammenfassung:Aims Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high‐grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in‐situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used. Methods and results Digital whole slide images of haematoxylin and eosin‐stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry‐sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple‐hit or immunoglobulin‐partner FISH‐based designations or clinical outcome measures. Conclusions Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC‐rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.
Bibliographie:Delphine Maucort‐Boulch and Maria Calaminici contributed equally to this study.
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ISSN:0309-0167
1365-2559
1365-2559
DOI:10.1111/his.14896