Hepatosplenic and subcutaneous panniculitis-like γ/δ T cell lymphomas are derived from different Vδ subsets of γ/δ T lymphocytes

Gamma/delta T cell lymphomas (γ/δ TCL) represent rare, often aggressive types of T cell malignancy that are clinically and pathologically diverse. Most γ/δ TCL occur as a hepatosplenic or subcutaneous type. To date, analysis of the T cell receptor δ (TCRδ) gene repertoire of hepatosplenic γ/δ TCL (γ/δ HSTCL) and subcutaneous panniculitis-like γ/δ TCL (γ/δ SPTCL) has been reported only in a limited number of cases. In this study we analyzed 11 γ/δ HSTCL and 4 γ/δ SPTCL by polymerase chain reaction and immunostaining to determine their usage of the Vδ subtypes (Vδ1-6). It is noteworthy that 10 of 11 γ/δ HSTCL expressed the Vδ1 gene. The remaining case also expressed T cell receptor δ (TCRδ) as determined by flow cytometry and TCRδ rearrangement in Southern blot. However, the Vδ gene expressed by this lymphoma could not be determined, which suggests usage of an as yet unidentified Vδ gene. In striking contrast to the γ/δ HSTCL, all 4 γ/δ SPTCL expressed the Vδ2 gene. Our data demonstrate that γ/δ HSTCL are preferentially derived from the Vδ1 subset of γ/δ T lymphocytes, whereas γ/δ SPTCL are preferentially derived from the Vδ2 subset. The pattern of Vδ gene expression in HSTCL and SPTCL corresponds to the respective, predominant γ/δ T cell subsets normally found in the spleen and skin. This finding suggests that γ/δ TCL are derived from normal γ/δ T lymphocytes which reside in the affected tissues. Furthermore, the selective, lymphoma type-specific Vδ gene segment usage may provide a molecular tool to distinguish better among various types of γ/δ TCL lymphoma particularly in the clinically advanced, widely disseminated cases.