Abstract:

Background and purpose: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) with gene rearrangement of MYC, BCL2 and BCL6, also known as triple-hit lymphoma (THL), has a low incidence and relevant literature is limited. Thus comprehensive and sufficient understanding is lacking. The purpose of this study was to explore the clinicopathological features and prognosis of this rare disease. Methods: Ten cases of THL diagnosed in Department of Pathology, Fudan University Shanghai Cancer Center from June 2016 to December 2021 were collected. Clinical features were analyzed retrospectively. Histopathological features were observed using H-E stain. Immunophenotype was analyzed by immunohistochemistry. The rearrangement of MYC, BCL2 and BCL6 genes was detected by fluorescence in situ hybridization (FISH), and Epstein-Barr virus (EBV) infection was detected by in situ hybridization using EBV-encoded RNA (EBER). Results: Of the 10 cases, 4 cases were male and 6 cases were female. The median age was 54 years (43-80 years). Two cases occurred in lymph nodes, 6 cases involved extranodal organs, and both lymph nodes and extranodal organs were involved in the other 2 cases. There were 4 cases (40%) with clinical stage Ⅲ/Ⅳ disease and 6 cases (60%) with clinical stage Ⅰ/Ⅱ disease. 40% (4/10) patients had international prognostic index (IPI) score ≥3. 50% (4/8) patients had bone marrow invasion. Two (20%) cases had B symptoms. 40% (4/10) patients had a history of hepatitis B virus infection. Five cases had the morphology of DLBCL, not otherwise specified (DLBCL-NOS); Two cases showed morphological features intermediate both DLBCL and Burkitt lymphoma; One case had a blastoid cytomorphology, and the other 2 cases failed to be classified accurately because of serious crushing artifacts of the tissue. Immunophenotypically, 80% of the cases were of germinal center B-cell (GCB) type and 20% were of non-GCB type. MYC/BCL2 double expression accounted for 78% (7/9), BCL6 positivity was found in 80% of the total cases, and the Ki-67 proliferation index was ≥80% in all cases. FISH showed that all 10 cases had MYC, BCL2 and BCL6 gene translocation rearrangement. EBV infection was consistently absent. All except one case received systemic treatment. The overall survival was 2.0-55.5 months (median, 16.8 months), and 1-year overall survival rate was 68.6%. The 1-year overall survival rates of patients with stage Ⅰ/Ⅱ disease and stage Ⅲ/Ⅳ disease were 100% and 25% respectively. Conclusion: THL mainly affects middle-aged and elderly patients, which occured more frequently in extranodal organs, and it is characterized by GCB immunophenotype and MYC/BCL2 double expression. A considerable number of patients have a clinical stage of Ⅰ/Ⅱ disease and a better prognosis in the current series, indicating that early identification of THL is of great importance for timely intervention and improving the prognosis.

Key words: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma, Triple-hit lymphoma, Gene rearrangement, Clinicopathological features, Immunophenotype, Survive