A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era: selecting cases, matching clinical benefit : A position paper from the Italian Group of Haematopathology (G.I.E.)

Abstract

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient.

Keywords: DLBCL; Diagnosis; Double hit; FISH; HGBL; MYC.

Fig. 1

Morphological features of aggressive mature B cell lymphomas. In DLBCL, the cells are pleomorphic with centroblastic and/or immunoblastic features. Blastoid cells are medium-sized cells with a fine chromatin pattern and inconspicuous nucleoli. Cases with features overlapping between BL and DLBCL (BCLU) show medium-sized cells, less monomorphic than in classical BL, with multiple paracentrally located nucleoli and frequent starry sky pattern

Fig. 2

Interphase FISH showing rearrangements of MYC, BCL2, and BCL6 genes using dual color break-apart (BA) probes. MYC/IGH translocation is detected using a dual color dual fusion FISH probe

Fig. 3

Diagnostic workflow for the diagnosis of aggressive mature B cell lymphomas . The workflow applies to DLBCLs that don’t fulfill the inclusion criteria for the specific DLBCL entities (i.e. primary mediastinal B cell lymphoma (PMBCL), intravascular DLBCL, EBV+ DLBCL, T cell rich histiocyte rich B cell lymphoma (TCRHRBCL), etc (*) and to blastoid lymphomas excluding lymphoblastic lymphomas and mantle cell lymphomas (**). In DLBCL discussion with the referring hematologist is highly recommended before proceeding with FISH analyses (***).