c-Myc Amplification in Non Hodgkin’s-Lymphomas with Burkitt-Like Features Is Associated with a Poor Prognosis.

We retrospectively studied 15 newly diagnosed patients presenting with NHL and Burkitt-like cells (BLCs) after morphological examination and histology review (lymph-nodes: 7 cases, peripheral blood: 5 cases, bone marrow: 3 cases and spleen: 1 patient). Conventional cytogenetic analyses were performed at diagnosis on lymph nodes biopsies (n=6), peripheral blood lymphocytes (n=4), bone marrow (n=4) or spleen (n=1). FISH studies used commercially available probes: IGH/c-MYC fusion signals probes, IGH/Bcl-1 fusion signals probes, IGH/Bcl-2 fusion signals probes and c-Myc 8q24 probe to detect t(8;14)(q24;q32), t(11;14)(q13;q32), t(14;18)((q32;q21) and c-Myc amplification, respectively. Morphological examination and/or histology showed BLCs in all patients. Burkitt-like lymphoma (BLL) is a highly proliferative lymphoma that morphologically resembles Burkitt’s lymphoma (BL) but has more polymorph and pleiomorph cells or large lymphoid cells than BL. The mean percentage of Ki-67 positive cells was 80% (range, 70–100%). A normal karyotype was present in 3 cases and a complex karyotype was observed in 12 cases (80%). When combining conventional cytogenetic studies and FISH studies, t(8;14) or the variants t(2;8) or t(8;22) were never detected. In contrast t(11;14)(q13;q32) was found in 4 cases and t(14;18) in 6 cases. Interestingly, c-Myc amplification was observed in all cases with 3 to more than 9 copies in 10–77% metaphase or interphase cells. The diagnosis of follicular lymphoma (FL) was confirmed by a CD5⁻ and CD10⁻ immunologic profile, typical t(14;18) in 4/6 cases and IgH/Bcl-2 fusion gene in all cases. Four cases were classified as mantle cell lymphoma (MCL) with a blastoid variant: MCL diagnosis was established by lymph-node biopsy in 1 case, CD5+ and CD23+ expression in 3/4 cases and 2/4 cases respectively, typical t(11;14)(q13;q32) in 3 cases, complex caryotype including 11 and 14 chromosomal abnormalities in 1 case and IgH/Bcl-1 fusion gene in all cases. Two patients had marginal MZL with a CD5⁻ and CD10⁻ profile and a complex caryotype including +3 and +18. Two patients presented a DLBCL (CD19⁺, CD20⁺) with BLCs and one case was classified as T-NHL (CD2+, CD4+, T-cell receptor gene rearrangements) in leukemic phase with BLCs. All these 15 patients have a poor prognosis with a death occurring in 6 patients during the first month after diagnosis. The presence of BLCs was observed independently of the type of lymphomas, FL, MCL or MZL. c-MYC amplification was associated with BLCs and progressive disease. In conclusion, we identified a new subgroup of patients with NHL (14 B-NHL, 1 T-NHL) and a profile including a poor prognosis, Burkitt-like features at presentation without t(8;14)(q24;q32) or its variants and Myc amplification in all cases.