Biphenotypic Gamma-Delta T-Cell Leukemia/Lymphoma with Coexpression of Pax-5 and Other B-Cell Specific Antigens.

Lineage commitment of B- and T-lymphocytes occurs in early stages of normal differentiation. Pax-5 promotes commitment of B-cell and blocks early development of T-cell. Under neoplastic conditions, aberrant expression of less specific T-cell antigens (CD2, CD5 and CD8) has been detected in certain B-cell lymphomas, and B-cell antigens CD20 and CD79a have been seen in rare cases of T-cell lymphomas. However, coexpression of true lineage specific B-cell antigens Pax-5 and CD19 in T-cells with surface CD3 and T-cell receptors has not been reported in either normal or neoplastic T-cells. We report 4 cases of aggressive T-cell lymphoma/leukemia with a consistent but unusual immunophenotype, which was determined by immunohistochemistry (IHC) in all four cases with paraffin embedded tissue and by flow cytometry (FCM) in 2/4 cases. Molecular and cytogenetic analyses were also attempted in two patients and clinical information will be provided. All patients were male aged 21-79 years. Three patients, including 2 cases of T-ALL, presented with generalized lymphadenopathy and bone marrow involvement (clinical stage IV); 1/3 also had splenic involvement. A distinct mediastinal mass was not identified in any of the patients. Two patients undergoing therapy received the hyper-CVAD regimen and had a poor response to early treatment. One of the two was subsequently treated with Campath without success. The 4th patient presented with an isolated chest wall mass. Detailed clinical information is currently unavailable for 2 patients. In all cases, the neoplastic cells were characterized by blastic morphology and coexpression of bilineage lymphoid antigens. The neoplastic cells in 3 cases with systemic disease were immunoreactive with T-cell antigens CD3, CD5, CD7, CD43, and B-cell antigens CD79a and Pax-5; 2/3 cases that had FCM data both showed expression of CD19 and surface γ/δ-TCR, as well as myeloid antigens CD11c and CD33. The case without FCM data lacked βF1 (α/β-TCR) expression by IHC. In addition, 2/3 cases also had immunophenotypic features of typical T-lymphoblastic leukemia or lymphoma (T-ALL) (CD34+ and TdT+). All three cases lacked NK cell antigen CD56 and T-cell antigen CD2, and were double negative for CD4 and CD8. The tumor cells from the 4th case were positive for all pan-T cell antigens (CD2, CD3, CD7, CD43) except CD5 by IHC, and were double negative for CD4 and CD8. These features were phenotypically consistent with a γ/δ-T cell lymphoma, which was also supported by lack of detectable βF1 expression. Similar to other cases, however, these cells were also positive for B cell antigens Pax-5 and CD79a, as well as CD20. The only patient who had successful molecular and cytogenetic analyses had isochromosome 9 and clonal TCR gamma gene rearrangement. In summary, T-cell lymphoma or leukemia with bi-lineage lymphoid antigens is associated with Pax-5 expression, which may account for the upregulation of CD19. It appears to be a rare disease of γ/δ-T-cell origin with a unique phenotypic profile. Further study is needed to determine if the observed i(9) involves disruption of the Pax-5 locus at 9q13.