High-grade B-cell lymphoma: a term re-purposed in the revised WHO classification

The designation high-grade B-cell lymphoma traditionally has been used as a general term for B-cell lymphomas that are morphologically aggressive with many mitotic figures, often a starry-sky pattern, and a high proliferation rate as shown by Ki-67 expression. These morphological features correlate with aggressive clinical behaviour. In the 2017 revision of the World Health Organization (WHO) classification of lymphomas, the term high-grade B-cell lymphoma has been re-purposed. Most cases in this category include so-called double and triple-hit lymphomas in the subgroup designated high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements. A smaller subset of cases are designated as high-grade B-cell lymphoma, not otherwise specified (NOS). This group is stated to be heterogeneous and includes neoplasms without double/triple-hit genetics as well as neoplasms that do not readily fit within the categories of diffuse large B-cell lymphoma NOS or Burkitt lymphoma. In most cases, accurate diagnosis can be achieved by integration of morphological, immunophenotypic and conventional cytogenetic and/or fluorescence in situ hybridisation (FISH) results. However, a few cases of high-grade B-cell lymphoma show overlapping features with different entities and can cause diagnostic difficulties. The WHO scheme is generally based on a ‘snapshot’ of current knowledge and, in our opinion, does not entirely capture the current state of knowledge of high-grade B-cell lymphomas. In this article, we review the topic of high-grade B-cell lymphoma as is currently described in the WHO classification, address recent developments, discuss difficulties one can encounter when applying the WHO scheme in daily practice, and we present some suggestions for the diagnostic workup of high-grade B-cell lymphomas.