High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements

c-MYC/BCL2 HGBL DH, c-MYC/BCL6 HGBL DH and HGBL NOS are different entities that are represented in some cases by transformed from low-grade lymphomas (tLGLs): follicular (FL) or marginal zone lymphoma (MZL).

To distinguish the group of tLGLs from de novo HGBLs.

We have analyzed the data of 99 HGBL patients: 6-HGBL TH, 26-c-MYC/BCL2 HGBL DH, 16-c-MYC/BCL6 HGBL DH and 51-HGBL NOS. We suggested an integral transformation index (ITI) indicating the probability of HGBLs development from tLGLs. It included: histologic signs of transformation (HST), lymphoma history ≥4 months, discordant bone marrow involvement, paraprotein secretion, and minimal disseminated disease in blood by flow cytometry. Comparison of groups was carried out using χ2 test. Differences were considered significant at p<0.05 (STATISTICA 12.0).

Morphological signs of tLGLs were revealed in 3 patients with HGBL TH, 11 patients with c-MYC/BCL2 HGBL DH (from FL), 6 patients with c-MYC/BCL6 HGBL DH (from MZL), and 4 of patients with HGBL NOS (1 from FL and 3 from MZL). ITI increased probability to reveal tLGLs among HGBLs compared with morphological study only from 8% to 67% among HGBL NOS (p=0.001), from 42% to 62% among c-MYC/BCL2 HGBL DH, from 38% to 81% among c-MYC/BCL6 HGBL DH (p=0.01) and from 50% to 83% among HGBL TH. c-MYC/BCL2 HGBL DH and HGBL TH predominantly attended to GCB-subtype (93%), c-MYC/BCL6 HGBL DH to non-GCB (54%), (p=0.03). ITI score at least 1 point correlated with central nervous system (CNS) involvement (p=0.008). Paraprotein secretion was observed only in c-MYC/BCL6 HGBL DH or HGBL NOS patients.

ITI distinguishes cases of tLGLs among HGBLs. c-MYC/BCL2 HGBL DH and HGBL TH are frequently presented by GCB-lymphomas transformed from FL. c-MYC/BCL6 HGBL DH and HGBL NOS can develop from MZL with paraprotein secretion. Involvement of the CNS is characteristic of tLGLs.

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p < 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.