The t(14;18)(q32;q21) with extra MYC signal - is it a gray zone lymphoma?

Double-hit lymphomas (DHL) are defined as B-cell lymphoma with a chromosomal breakpoint affecting the MYC/8q24 locus in combination with rearrangement at (14;18)(q32;q21). We recently observed three cases of B-cell lymphoma with an extra intact MYC signal in association with the t(14;18)(q32;q21) translocation. The impact of an extra copy of MYC to the clinical course and prognosis of one patient with Diffuse Large B Cell Lymphoma (DLBCL) and two patients with Follicular Lymphoma (FL) was evaluated. Flow cytometry in all cases demonstrated lambda- or kappa-light chain restricted CD20 and CD10 positive neoplastic B cells. FISH analysis was negative for MYC gene rearrangement but demonstrated an extra copy of intact MYC. Tissue sections displayed typical starry sky "gray zone" lymphoma morphology in case of DLBCL and FL morphology in cases 2 and 3, with high Ki67 labeling in all three cases. All patients responded well to initial chemotherapy although displayed variant outcome after initial remission. The patient with DLBCL deceased within a year of diagnosis while the other two patients with FL showed much better overall survival. Our limited experience showed that additional copy of intact MYC may be equivalent to "classic" DHL on the background of DLBCL with additional cytogenetic abnormalities, however isolated t(14;18)(q32;q21) translocation in combination with additional copy of intact MYC may demonstrate histology and clinical outcome more comparable with "classic" low grade follicular lymphoma, albeit with more aggressive morphology.