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Heterogeneity or change in cell of origin in diffuse large B-cell lymphomas determined using hans algorithm
Akiko Miyagi Maeshima1, Hirokazu Taniguchi2, Yuka Takahashi1
1Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Insights
Cell of origin (COO) heterogeneity was analyzed in diffuse large B-cell lymphoma (DLBCL). COO changed in 19% of DLBCL cases, suggesting re-examination of COO in new biopsies for optimal treatment.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease.
- Cell of origin (COO) classification, such as germinal center B-cell (GCB) and non-GCB, impacts prognosis and treatment.
- Understanding COO stability is crucial for effective DLBCL management.
Purpose of the Study:
- To investigate the heterogeneity and change in COO within DLBCL patients.
- To analyze COO stability across different disease phases and sample sites.
- To identify factors associated with COO changes in DLBCL.
Main Methods:
- Utilized the Hans algorithm for COO classification based on immunohistochemical staining (CD10, BCL6, MUM1).
- Analyzed multiple DLBCL specimens from 156 patients, including initial diagnosis, simultaneous biopsies, and relapse samples.
- Correlated COO changes with specific marker expression patterns.
Main Results:
- COO was initially classified as GCB in 32% and non-GCB in 68% of patients.
- COO remained stable in 81% of patients but changed in 19% (GCB to non-GCB or vice versa).
- COO heterogeneity was observed in 14% of simultaneous samples, 7% of primary refractory sites, and 20% of relapse samples. Specific marker patterns showed varying rates of COO change (0-37%).
Conclusions:
- A significant proportion of DLBCL cases (19%) exhibit heterogeneous or changing COO.
- COO instability is more prevalent in certain disease phases and sample locations.
- Re-evaluation of COO in additional biopsy samples is recommended for personalized treatment strategies in DLBCL.
Abstract:
This study aimed to analyze the heterogeneity or change in cell of origin (COO) in diffuse large B-cell lymphoma (DLBCLs) using the Hans algorithm including 156 patients with multiple DLBCL specimens. COO was detected via immunohistochemical staining for CD10, BCL6, and MUM1. The COO of the main tumor at initial diagnosis was germinal center B-cell (GCB) and non-GCB type in 50 (32%) and 106 (68%) patients, respectively. It did not change in 126 patients (81%). However, it changed in 30 patients (19%), from GCB to non-GCB in 12 patients and vice versa in 18 patients. The COO was heterogeneous or changed in 14% of simultaneous samples at other sites during the initial diagnosis, in 7% of primary refractory sites, and in 20% of samples obtained in the relapse phase other than the primary site. Changes in CD10, BCL6, and MUM1 expression were observed in 15%, 23%, and 24% samples, respectively. A low incidence of change in COO was observed in DLBCL with CD10+/BCL6+/MUM1- (4%), CD10-/BCL6-/MUM1+ (3%), and CD10-/BCL6-/MUM1- (0%) patterns, whereas DLBCL with other patterns showed COO changes at rates of 20-37%. In conclusion, COO was heterogeneous or changed in 19% of DLBCL cases. The COO should be re-examined in other biopsy samples to determine the optimal treatment.

