The WHO term, ‘high-grade B-cell lymphoma’ (HGBL) encompasses aggressive B-cell neoplasms that differ biologically and clinically from diffuse large B-cell lymphoma (DLBCL), NOS (not other-wise specified). There are two categories: (1) HGBL with co-occurrence of MYC and BCL2 and/or BCL6 rearrangements also called ‘double or triple hit’ lymphomas and (2) HGBL, NOS which comprises cases that have either blastoid morphology or have features intermediate between DLBCL and Burkitt lymphoma but lack the combination of genetic alterations that define the former group . Cases that in the 2008 WHO classification were designated ‘B-cell lymphoma unclassifiable with intermediate features between DLBCL and Burkitt lymphoma’ can fall into either of these categories, depending on the underlying genetic abnormality.
HGBL with concomitant rearrangement of MYC and BCL2 and/or BCL6
According to the WHO classification, this category comprises: (1) cases previously designated double hit unclassifiable B-cell lymphoma and (2) blastoid cases and those with the morphology of DLBCL having concomitant MYC and BCL2 and/or BCL6 rearrangement. Cases of grade 3B follicular lymphoma that have a double hit but do not have a DLBCL component are excluded from the HGBL category while cases of large cell transformation of follicular lymphoma with MYC and BCL2 and/or BCL6 rearrangement are regarded as HGBL transformation of follicular lymphoma (Figure 15.1). Cases with lymphoblastic leukaemia/lymphoma with the two rearrangements – including some that represent transformation of a known follicular lymphoma – are excluded from this category. Although cells from most but not all cases of HGBL with concomitant rearrangement of the above mentioned genes will express the proteins that they code for (MYC and BCL2 and/or BCL6), exclusive expression of the proteins – so-called double expressors – is not enough to categorize the case within this group since not all these cases carry the genomic rearrangements. Although double expressor lymphomas do not constitute a distinct entity they resemble HGBL in also having an aggressive clinical course and mostly an activated B-cell phenotype .
Diagnostic algorithm for high grade B-cell lymphoma (HGBL). BL, Burkitt lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; L/L, leukaemia/lymphoma.
This lymphoma represents about 8% of de novo DLBCL . It affects mainly elderly adults with a slight male predominance. Most patients present with advanced widespread disease. Extranodal and central nervous system involvement are present in about a half of the patients and bone marrow involvement in over a third. The International Prognostic Index is usually high.
The lymph node or other tissue involved shows a diffuse pattern of growth (Figure 15.2). The morphological features of the lymphoma cells are variable. Greater than half of the cases resemble DLBCL, NOS. The cells are larger ...