High-Grade Epstein-Barr Virus-Negative Biphenotypic Lymphoma with Expression of B- and T-Cell Markers and Leukemia Presentation: Case Report and Literature Review

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43x10(3)/mu L white blood cells, 11.2 g/dL hemoglobin, and 88x10(3)/mu L platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).