Lymphoproliferative disease of granular lymphocytes with T‐cell receptor gamma delta‐positive phenotype: restricted usage of T‐cell receptor gamma and delta subunit genes

Abstract

Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by more than 0.5 x 109/L of proliferating granular lymphocytes in the peripheral blood. Because of its rarity, the characteristics of LDGL with T-cell receptor (TCR) gammadelta phenotype (gammadeltaT-LDGL) have not yet been identified. This report describes the clinical, hematological, and immunological findings of four patients with this disease. In two cases, the clinical course was indolent and the other two patients required various therapies. The cells had a common immunophenotype: CD3+, CD4-, CD16+, CD56-, CD57-, CD122-, TCR-gammadelta+, and three were CD8-positive. The immunopurified TCR-gammadelta cells from the patients expressed only Vgamma9 and Vdelta1. Spectratyping and sequencing showed mono- or oligoclonality for TCRgamma and TCRdelta subunit genes. Soluble Fas ligand in sera was significantly elevated in all patients. These findings suggest that gammadeltaT-LDGL qualifies as a distinct disease entity.

Flow cytometric immunophenotypic profiles of mature gamma delta T‐cell malignancies involving peripheral blood and bone marrow

“…Because gamma delta T-cell LGL leukemia is rare, we reviewed the literature for other cases with adequate immunophenotypic data for comparison ( Table 2). The immunophenotypic data reported here are similar to those in the literature (10,(13)(14)(15). CD2 and CD3 were positive and CD4 negative.…”

“…However, gamma delta T-cell LGL leukemias have a very indolent clinical course with symptoms (increased and recurrent infections) primarily resulting from neutropenia and not from the gamma delta T-cell process. Patients with gamma delta T-cell LGL leukemia in the present study and in the literature demonstrated good survival despite receiving minimal therapy, such as cyclosporin, or no therapy (13)(14)(15). The more aggressive and more common gamma delta T-cell hepatosplenic lymphoma has frequent involvement of bone marrow (72% of cases) and peripheral blood (50% of cases) and, similar to gamma delta T-cell LGL leukemias, can present initially with abnormal peripheral blood findings (3)(4)(5).…”

“…CD2 and CD3 were positive and CD4 negative. CD8, CD5, CD16, and CD57 expressions were higher than those observed in other gamma delta T-cell malignancies where they were uncommon (Table 3) (10,(13)(14)(15). Light scatter characteristics of the gamma delta T-cell LGL leukemias studied were not distinctive.…”

“…Although hepatosplenic gamma delta T-cell lymphoma is the prototypic gamma delta T-cell neoplasm, mucocutaneous gamma delta T-cell lymphoma and gamma delta T-cell LGL leukemia have been described (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). With the exception of gamma delta T-cell LGL leukemia, these malignancies have a poor prognosis and require aggressive chemotherapy.…”

“…Patients present with a clonal peripheral blood gamma delta T-cell lymphocytosis, neutropenia, and recurrent bacterial infections; bone marrow involvement is ubiquitous. Patients have an indolent course with symptoms that are related to the neutropenia and include fever and recurrent bacterial infections (8,10,(13)(14)(15). The indolent clinical course makes it important to differentiate gamma delta T-cell LGL from other clonal gamma delta T-cell lymphoproliferative processes, especially hepatosplenic gamma delta T-cell lymphoma, which frequently involves the blood and bone marrow.…”