Clinicopathological analysis of follicular lymphoma with BCL2, BCL6, and MYC rearrangements

Most follicular lymphomas (FL) show t(14;18)/IGH‐BCL2 translocation, but rearrangement (R) negative cases exist. A series of 140 FL patients with a BCL2, BCL6, and MYC gene status examined by fluorescence in situ hybridization (FISH) were classified into five groups: (a) BCL2‐R group (BCL2‐R/BCL6‐G/MYC‐G) (G, germline), 77 cases; (b) BCL2/BCL6 double‐R group (BCL2‐R/BCL6‐R/MYC‐G), 16 cases; (c) BCL6‐R group (BCL2‐G/BCL6‐R/MYC‐G), 16 cases; (d) MYC‐R group (BCL2‐R or G/BCL6‐R or G/MYC‐R), three cases; (e) Triple‐G group (BCL2‐G/BCL6‐G/MYC‐G), 28 cases. The BCL6‐R group had different clinicopathological characteristics. It showed lower rates of an advanced clinical stage and bone marrow invasion, less disease progression (p = 0.036), and a ‘trend’ toward a favorable progression‐free survival (PFS) (p = 0.06). It also showed higher rates of grade 3A and MUM1‐expression, and when analyzing the interfollicular spread pattern of CD20‐positive cells, had fewer cases showing the IF3+ pattern (high interfollicular spread). Moreover, cases with BCL6‐R and/or BCL6 gain (with cases of BCL2 rearrangement and/or of copy number gain excluded) correlated with favorable PFS (p = 0.014) and less IF3+ pattern (p = 0.007). We demonstrated that BCL6‐R FLs showed unique clinicopathological findings, and FISH of BCL2, BCL6, and MYC is useful for FL diagnosis and clinical management.