Abstract
Introduction: Chromosomal translocations are common in non-Hodgkin’s lymphomas (NHL), most frequently involving the genes bcl-2 in the t(14;18) of follicular lymphoma (FL), c-myc in the t(8;14) of Burkitt’s lymphoma (BL) and bcl-6 in the t(3;14) of follicular or diffuse large B-cell (DLBC) lymphoma. We report the clinical features, pathology and genetic findings in an exceedingly rare case of Burkitt’s lymphoma that showed concurrent involvement of these three chromosomal loci.
Case Report: This is a 65 year old Caucasian female who presented with a rapidly growing right supraclavicular lymph node over a few weeks. FNA biopsy showed typical morphology of Burkitt’s lymphoma. Similar morphologic features were found on the bone marrow biopsy. There was widespread disease with no CNS involvement. Flow cytometry from peripheral blood and immunohistochemistry on the cellblock showed B-cell phenotype positive for CD 10, CD19, CD20 (negative CD20 by immunohistochemistry), HLA-DR, cytoplasmic CD79a, and negative for CD34 and TdT. The interesting finding was the lack expression of surface or cytoplasmic immunoglobulin and expression of weak Bcl-6. Almost 90–95% expressed Ki67. The cytogenetic analysis reportedly demonstrated a complex karyotype t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). After 7 cycles of hyper CVAD-R she had bone marrow biopsy which showed residual disease. She also had a biopsy confirmed relapse as left arm nodule and left leg nodular infiltrate at 8 and 12 months form the diagnosis, respectively.
Discussion: This is a complex case of high grade B-cell lymphoma with morphology suggestive of Burkitt’s lymphoma. However the classification was challenging by the lack of surface immunoglobulin expression that might be expected in mature B-cell neoplasm “DLBCL, FL”, and the lack of TdT and CD34 that might be expected in precursor B-cell neoplasm “BL”. The diagnosis was highly dependent on the cytogenetic findings, which was significant for the presence of t(8;14) albeit in a three way translocation t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). The lymphoma was therefore described as “Burkitt’s transformation”. This is a rare translocation pattern, but has been described in follicular lymphoma, grade 3; diffuse large cell lymphoma; and Burkitt’s lymphoma.
Conclusion: BL might lack surface immunoglobulin expression making the diagnosis of high grade B-cell lymphoma challenging if based on the morphology and immunophenotyping alone. The cytogentetic findings better delineate sub-types of lymphoma. Molecular evidence of multiple oncogene deregulations, especially when involving the c-myc gene, appears to be associated with a dire clinical outcome.
EBV-positive low-grade follicular lymphoma transforming to EBV-negative high-grade B-cell lymphoma with MYC and BCL2 rearrangements
