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 (gamma/delta TCL) represent rare, often aggressive types of T cell malignancy that are clinically and pathologically diverse. Most gamma/delta TCL occur as a hepatosplenic or subcutaneous type. To date, analysis of the T cell receptor delta (TCR delta) gene repertoire of hepatosplenic gamma/delta TCL (gamma/delta HSTCL) and subcutaneous panniculitis-like gamma/delta TCL (gamma/delta SPTCL) has been reported only in a limited number of cases. In this study we analyzed 11 gamma/delta HSTCL and 4 gamma/delta SPTCL by polymerase chain reaction and immunostaining to determine their usage of the VS subtypes (V delta 1-6). It is noteworthy that 10 of 11 gamma/delta HSTCL expressed the V delta 1 gene. The remaining case also ex pressed T cell receptor delta (TCR delta) as determined by how cytometry and TCR delta rearrangement in Southern blot. However, the V delta gene expressed by this lymphoma could not be determined, which suggests usage of an as yet unidentified V delta gene. In striking contrast to the gamma/delta HSTCL, all 4 gamma/delta SPTCL expressed the V delta 2 gene. Our data demonstrate that gamma/delta HSTCL are preferentially derived from the V delta 1 subset of gamma/delta T lymphocytes, whereas gamma/delta SPTCL are preferentially derived from the V delta 2 subset. The pattern of V delta gene expression in HSTCL and SPTCL corresponds to the respective, predominant gamma/delta T cell subsets normally found in the spleen and skin. This finding suggests that gamma/delta TCL are derived from normal gamma/delta T lymphocytes which reside in the affected tissues. Furthermore, the selective, lymphoma type-specific V delta gene segment usage may provide a molecular tool to distinguish better among various types of gamma/delta TCL lymphoma particularly in the clinically advanced, widely disseminated cases.