The introduction of new lymphoma entities that are defined by chromosomal rearrangements has led to changes concerning the diagnostic algorithms in routine hematopathology, particularly for the large group of aggressive B‑cell lymphomas. The new, genetically defined entity high-grade B‑cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma) is morphologically heterogenous and comprises lymphomas with the morphology of a diffuse large B‑cell lymphoma (DLBCL), but also cases with blastoid appearance as well as intermediate/Burkitt-like morphology. This implies a cytogenetic analysis for the final classification of aggressive lymphomas with DLBCL morphology, which constitute the most common lymphomas in daily practice. This analysis is currently most efficiently performed via a sequential fluorescence in situ hybridization (FISH) approach, with an initial MYC-FISH, that is followed (if required, i.e., if a MYC rearrangement is detected) by an analysis regarding a BCL2- and BCL6-chromosomal rearrangement. In addition, the update of the fourth edition of the WHO classification for hematopoietic neoplasms introduced additional lymphoma subgroups that are defined by chromosomal rearrangements, such as Burkitt-like lymphoma with 11q aberration as well as large B cell lymphoma with IRF4 rearrangement. Therefore, FISH currently plays an important role in the diagnostic armamentarium in routine diagnostic hematopathology.
Keywords: BCL2-translocation; BCL6-translocation; Burkitt lymphoma; FISH; High-grade B‑cell lymphoma; MYC rearrangement.