Ann Lab Med.  2020 Sep;40(5):361-369. 10.3343/alm.2020.40.5.361.

Diagnostic Approach for Double-Hit and Triple-Hit Lymphoma Based on Immunophenotypic and Cytogenetic Characteristics of Bone Marrow Specimens

• Kim H
• Kim HJ
• Kim SH

• KMID: 2502566
• DOI: http://doi.org/10.3343/alm.2020.40.5.361

Abstract

Background
High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 (BCL2/BCL6), also known as double-hit lymphoma (DHL) and/or triple-hit lymphoma (THL), is a new entity of B-cell lymphoma in the 2017 WHO Classification. We retrospectively investigated D/THL and their clinico-laboratory features among cases of large B-cell lymphoma involving the bone marrow (BM), including diffuse large B-cell lymphoma, Burkitt lymphoma, and B-cell lymphomas with medium to large lymphoid cells, by additional FISH analysis of BM aspirates.
Methods
A total of 111 patients diagnosed with aggressive B-cell lymphomas or B-cell lymphoma involving the BM with medium to large-sized malignant lymphocytes were reviewed from January 2000 to January 2018. Patients with available BM aspirates were evaluated by immunophenotyping by flow cytometry, chromosome, and FISH analysis for MYC and/or BCL2/BCL6 rearrangements.
Results
In total, 23/111 (20.7%) showed MYC rearrangement, and eight (7.2%) were reclassified as D/THL on BM after FISH analysis for MYC and BCL2/BCL6. The detection of CD5(-)/CD10(+) based on flow cytometry was strongly associated with D/THL. A complex karyotype with aberrations related to regions in MYC and BCL2/BCL6 was significantly associated with D/THL. When the MYC FISH results of 28 BM aspirates and formalin-fixed paraffin-embedded tissue specimens were compared, 14% were discrepant.
Conclusions
Immunophenotypic and cytogenetic characteristics facilitate the diagnosis of D/THL in the cases with BM-involving aggressive B-cell lymphomas.

Keyword

Double-hit lymphoma; Triple-hit lymphoma; Diffuse large B-cell lymphoma; Burkitt lymphoma; Aggressive B-cell lymphoma; MYC; BCL2; BCL6

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