Hepatosplenic and Subcutaneous Panniculitis-Like γ/δ T Cell Lymphomas Are Derived from Different Vδ Subsets of γ/δ T Lymphocytes

Abstract

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 (TCRS) 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 Vdelta subtypes (Vdelta1-6). It is noteworthy that 10 of 11 gamma/delta HSTCL expressed the Vdelta1 gene. The remaining case also expressed T cell receptor delta (TCRS) as determined by flow cytometry and TCRdelta rearrangement in Southern blot. However, the Vdelta gene expressed by this lymphoma could not be determined, which suggests usage of an as yet unidentified Vdelta gene. In striking contrast to the gamma/delta HSTCL, all 4 gamma/delta SPTCL expressed the Vdelta2 gene. Our data demonstrate that gamma/delta HSTCL are preferentially derived from the Vdelta1 subset of gamma/delta T lymphocytes, whereas gamma/delta SPTCL are preferentially derived from the Vdelta2 subset. The pattern of Vdelta 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 Vdelta 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.

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

“…44 There are subsets of gd T cells that differ in their ontogeny as reflected by their time of appearance in the thymus, TCR gene usage, TCR combinatorial complexity and their locations and functions in the body. There is also corresponding preferential gd gene usage in gd-PTCL at different sites such as Vd1 in HSTCL 9,45 , Vd2 in primary cutaneous gd-PTCL 46 and Vg9Vd2 in ENKTL and gd-PTCL (NHS). 26,29 Consistent with these findings, the re-classified gd-PTCLs in this study exhibited extranodal disease and expressed Vg9, Vd2 mRNA at high levels.…”

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

“…It is an uncommon entity that exhibits distinctive clinicopathologic features, and gene usage analysis has indicated clonal Vd1-Jd1 rearrangements associated with these lymphomas. 130 Furthermore, the rare type of cutaneous TCRgd þ T-cell lymphomas express Vd2 and therefore appear to represent a clonal expansion of TCRgd þ T cells that normally reside in the skin. 131 Other clonal TCRgd proliferations include CD3 þ TCRgd þ LGL proliferations that comprise about 5% of all CD3 þ LGL and often show Vd1-Jd1 rearrangements (Table 19).…”

Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma

“…Whereas ␥␦ HS-TCL usually belongs to the V ␦ 1 subset, ␥␦ SPTCLs represent the V ␦ 2 subset. 17 Whereas HS-TCLs are composed of functionally immature cells lacking granzyme B and perforin, 12 most other gamma-delta T-cell lymphomas are derived from activated cytotoxic T cells and present preferentially in cutaneous or mucosal sites. 18 This clinical distribution corresponds to the distribution of normal gamma-delta T cells.…”

“…20 To our knowledge, approximately 40 cases of gammadelta cutaneous T-cell lymphoma have been reported. 6,7,14,16,17,[20][21][22][23][24][25][26][27][28][29][30] We recently described the clinical, histologic, and immunohistochemical features of primary cutaneous ␥␦ T-cell lymphoma. 6 CGD-TCL shows preferential involvement of the extremities with plaques, tumors, and subcutaneous nodules, some of which ulcerate.…”