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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Comparison of Ki-67 Labeling Index Patterns of Diffuse Large B-Cell Lymphomas and Burkitt Lymphomas Using Image
Yosep Chong1,2, Tae Eun Kim3, Uiju Cho4
1Department of Hospital Pathology, Yeouido St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 07345, Korea.
Insights
Ki-67 staining effectively differentiates Burkitt lymphoma (BL) from diffuse large B-cell lymphoma (DLBCL). This method offers high sensitivity and specificity, aiding in diagnosing these aggressive B-cell lymphomas.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma in Korea.
- Differentiating DLBCL from Burkitt lymphoma (BL) is challenging due to overlapping histological and immunohistochemical features.
- Epstein-Barr virus status also shows overlap, complicating differential diagnosis.
Purpose of the Study:
- To perform a comparative morphometric analysis of Ki-67 staining between DLBCL and BL.
- To investigate the proportional differences in Ki-67 expression to aid in differential diagnosis.
- To evaluate the Ki-67 labeling index as a potential biomarker for distinguishing DLBCL and BL.
Main Methods:
- Analysis of Ki-67 stained slides from 103 DLBCL and 29 BL cases.
- Pathological confirmation using a three-tier classification system (negative, 1+, 2+, 3+).
- Comparative analysis of Ki-67 expression across DLBCL subtypes (activated B-cell, germinal center B-cell) and BL, including DLBCL with high proliferation indices.
Main Results:
- Patients with DLBCL were older (62.1 years) than those with BL (51.0 years).
- BLs had significantly lower proportions of negative Ki-67 cells (5.9%) compared to DLBCLs (12.4%).
- BLs exhibited significantly higher proportions of 3+ Ki-67 positive cells (96.3%) than DLBCLs (62.0%).
- A cut-off of 97.9% for 2+/3+ Ki-67 positive cells differentiated BL and DLBCL with 98.1% sensitivity and 100.0% specificity.
Conclusions:
- The Ki-67 labeling index demonstrates significant proportional differences between BL and DLBCL.
- Ki-67 staining serves as a valuable differential biomarker for distinguishing between DLBCL and BL.
- This quantitative approach enhances diagnostic accuracy for these aggressive lymphomas.
Abstract:
Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.

