An immunohistochemical germinal center B-cell dark zone signature identifies Burkitt lymphoma and molecular high-grade B-cell lymphomas.

OBJECTIVE

We hypothesized that a set of immunohistochemistry (IHC) stains could be used to distinguish Burkitt lymphoma (BL), the quintessential B-cell lymphoma with a germinal center B-cell (GCB) dark zone (DZ) expression signature, from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). This might also be applicable to high-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 rearrangements (double-hit lymphomas [DHLs]) and triple-hit lymphomas (THLs).

METHODS

A 5-marker IHC algorithm was designed from gene lists that distinguish physiologic DZ from light zone GCBs.

RESULTS

In training and validation cohorts, we distinguished BL from DLBCL, NOS with high sensitivity and specificity. Because DHLs/THLs are enriched for the gene expression DZ signature (DZsig), we evaluated 19 DHLs/THLs and 4 HGBCLs, NOS. Most (83%) cases were IHC DZ. The NanoString DLBCL90 assay was performed on 34 cases to correlate IHC DZ results with the molecular DZsig. The IHC DZ call was significantly associated with the DZsig (P = .0011). The sensitivity and specificity of IHC to recognize DZsig+ cases among DLBCL, NOS and DHLs with BCL2 rearrangements/THLs were 91% and 100%, respectively.

CONCLUSIONS

The IHC DZ algorithm can support a diagnosis of BL and identifies MYC-BCL2 DHLs/THLs with a molecular DZsig.