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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Challenges in Diagnosing High-grade B-cell Lymphoma, NOS: Poor Interobserver Agreement on Its Morphologic
Katrin S Kurz1, Sarah L Ondrejka2, Brett Collinge3,4
1Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart.
The American Journal of Surgical Pathology
|May 15, 2026
Summary
Diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS) lacks reproducibility among pathologists. Objective markers like dark zone signature may offer better classification than morphology alone for these aggressive B-cell lymphomas.
Area of Science:
- Hematopathology
- Oncology
- Molecular Biology
Background:
- High-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS) is morphologically intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL).
- Exclusion criteria for HGBCL, NOS include complex 11q aberrations or concurrent MYC- and BCL2- or BCL6-rearrangements.
- The diagnostic reproducibility of HGBCL, NOS has not been previously established.
Purpose of the Study:
- To assess the interobserver agreement in the diagnosis of HGBCL, NOS.
- To determine if HGBCL, NOS represents a distinct clinicopathologic entity.
- To explore the utility of objective markers, such as dark zone signature (DZsig), in classifying aggressive B-cell lymphomas.
Main Methods:
- Expert hematopathologists reviewed 92 cases initially submitted as HGBCL, NOS.
- Independent confirmation of diagnosis by at least 3/4 pathologists.
- Consensus review by a panel of 10-15 pathologists for cases with initial disagreement.
- Analysis of dark zone signature (DZsig) expression, MYC-rearrangements, and cell of origin.
Main Results:
- Only 39% (39/92) of initially submitted HGBCL, NOS cases were confirmed upon expert review, indicating poor interobserver agreement.
- 14% (13/92) of cases were reclassified as DLBCL.
- No significant differences in DZsig expression, MYC-rearrangements, or cell of origin were observed between initially submitted and confirmed HGBCL, NOS cases.
Conclusions:
- The morphological diagnosis of HGBCL, NOS demonstrates poor reproducibility, suggesting it may not be a distinct clinicopathologic entity.
- Molecular markers, such as DZsig, may provide more objective and reliable classification of aggressive B-cell lymphomas compared to morphology alone.
- Further research is needed to establish objective diagnostic criteria for aggressive B-cell lymphomas.
