Concurrent chromosomal translocations involving the BCL2 and MYC protooncogenes, so-called double-hit, is found both in diffuse large B-cell lymphoma (DLBCL) and in a newly defined B-cell lymphoma category with features overlapping between DLBCL and Burkitt lymphoma (BCLU, 2008 WHO classification). Few studies have been published on series of double-hit B-cell lymphomas, and to our knowledge only retrospective series, reporting an average frequency of around 5%. Therefore some authors suspected that the frequency of double-hit translocations was underestimated. In addition to unanimous reports of highly aggressive clinical behaviour; poor outcome and resistance to chemotherapy, double-hit lymphomas had GCB immunophenotype (Hans), varying morphology from classical Burkitt like to DLBCL-NOS and mostly high proliferation rates (Ki-67).
We conducted a prospective study of DLBCL to evaluate the frequency of double-hit BCL2/MYC translocations in DLBCL. Secondly, we wanted to analyse if any pathologic and/or clinical features correlated with the presence of a double-hit in order to evaluate the need for routine genetic analysis of large B-cell lymphomas in prognostic stratification.
All patients diagnosed with DLBCL or BCLU at the Haematopathology Section at Copenhagen University Hospital in Herlev were prospectively collected throughout 2009. Tumours were classified according to their morphology (2008 WHO classification), immunohistochemistry (CD10, BCL6, MUM1, BCL2, Ki-67) and FISH (BCL2, BCL6 and MYC translocations). Clinical data were collected from patient files.
Double-hit BCL2/MYC translocations were detected in 9 of 93 cases (10%); 7 DLBCL, 1 BCLU, 1 unclassified. All double-hit DLBCL were GCB immunophenotype and showed varying morphology. Ki-67 index ranged from 15–95%. Interestingly, 2 double-hit cases were late relapses (primary double-hit). Characteristic clinical parameters included a high International Prognostic Index (IPI) score, a high stage and an extranodal presentation.
In this prospective cohort of DLBCL patients the incidence of BCL2/MYC double-hit was 10%. This suggests that double-hit is more frequent in DLBCL than previously estimated. Double-hit lymphomas had GCB-immunophenotype but could not be identified by morphology or proliferation rate. Therefore if these patients should be identified due to an inferior prognosis (which we could not significantly establish due to limited observation time) routine FISH analysis for double-hit translocations should be performed in all patients with BCLU or DLBCL of GCB-subtype.
No relevant conflicts of interest to declare.
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