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. Histopathology Natkunam, Y., de Jong, D., Farinha, P., Gaulard, P., Klapper, W., Rosenwald, A., Sander, B., Tooze, R., Advani, R., Burton, C., Gribben, J. G., Kersten, M. J., Kimby, E., Lenz, G., Molina, T., Morschhauser, F., Scott, D., Sehn, L., Stevens, W., Clear, A., Baia, M., Habi, A., Elsensohn, M. H., Langlois-Jacques, C., Maucort-Boulch, D., Calaminici, M. 2023


Subclassification of large B-cell lymphoma (LBCL) is challenging due to the overlap in histopathologic, immunophenotypic, 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 fluorescent in situ hybridization (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study of how various histopathological features are used by a panel of eight expert hematopathologists.Digital whole slide images of hematoxylin and eosin-stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardized 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 cytologic 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 IG-partner FISH-based designations or clinical outcome measures.Our findings indicate that there are no specific conventional morphological parameters that help subclassify MYC-rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.

View details for DOI 10.1111/his.14896

View details for PubMedID 36849712