Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation

Abstract

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.

Immunophenotypic switch in cutaneous T‐cell lymphoma: A series of three cases and review of the literature

“…Many cases with IS were treated with multiple agents before the switch was documented on relapse. The most common IS reported in MF (13/15 cases) is a switch from a CD4‐positive/CD8‐negative profile without cytotoxic proteins to a CD4‐negative/CD8‐positive or CD4‐negative/CD8‐negative profile with expression of the cytotoxic markers TIA‐1 and granzyme B 1,3‐13 . Eighteen of 28 patients expired.…”

“…Eighteen of 28 patients expired. The average progression time from diagnosis of IS to death is 22 months with a range of (1‐76 months) 1,3‐14 . Notably, Merrill et al described 20 patients with a gamma delta phenotype and noted that CD8 expression appeared to change over time in two patients and CD30 changed over time in four patients, but detailed clinicopathologic information is not available for these cases 14 .…”

“…The underlying mechanism by which IS occurs is still unclear. Agbay et al proposed post‐therapy antigenic stimulation and clonal selection as a possible explanation 3 . As many cases of IS occur post therapy, it is possible that treatment might be contributing to this shift.…”

“…Immunophenotypic switch (IS) is defined as an alteration in the immunophenotypic expression of a tumor while retaining its genotypic signature and occurs during lymphoma progression 1 . It is a known phenomenon in hematologic malignancies, 2 but has rarely been reported in cutaneous T‐cell lymphoma (CTCL) 1,3‐14 and its clinical and biological significance is not well studied. IS poses a diagnostic challenge and may be associated with a worse prognosis 1,3‐14 .…”

A Systematic Approach to the Cutaneous Lymphoid Infiltrates: A Clinical, Morphologic, and Immunophenotypic Evaluation

“…More recently, several authors have identified some cases with a more protracted clinical course, MF-like clinical lesions, and epidermotropism. 182,183 Those cases are negative for CD56 and have expression of CD4 or CD8. It is believed that those cases may have a more indolent behavior compared with the classic forms of PCGDTCL.…”