TCR-γ Expression in Primary Cutaneous T-cell Lymphomas

Abstract

Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.

Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior

“…In cases of ENKTL, previous studies applying conventional PCR techniques showed wide ranges of T-cell clonality ranging from 0 to 71.4%, 5,6,18,19 while T-cell clonality ranged from 0 to 26% by BIOMED-2 multiplex PCR analysis. 7,8,10,20 The traditional PCR design with a few consensus primers to detect TCR gene rearrangement yields frequent falsenegative results because the primers cannot cover extensive sequence variations. On the other hand, a lack of further analysis of PCR products can produce false-positive results.…”

“…7,8,10,20 Rodriguez-Pinilla et al 10 showed that ENKTLs primarily affecting the skin or subcutaneous tissue (n = 11) were all negative for TCR-γ. Pongpruttipan et al 8 analyzed 67 cases of ENKTL by immunohistochemistry and found that TCR types including βF1, γ, and δ were negative in 70% of cases, positive in only 9%, and indeterminate in 21%.…”

“…The γδ T-cell phenotype is not necessarily associated with bad prognosis, as it can be found in cases with good and bad outcomes. 10 On the other hand, in cases of intestinal T-cell lymphoma, the NK-cell lineage predicts a worse prognosis compared with the T-cell lineage, irrespective of the presence of EBV. 11 There have been only few reports on the clinical impact of cellular lineage for cases of ENKTL.…”

Peripheral T cell lymphoma in Asia

“…Patients present with multiple nodules on the trunk and limbs or generalized ulcerated plaques. Its histological findings are variable and include upper dermal infiltration with marked epidermotropism with ulceration of the epidermis, diffuse dermal infiltration, or involvement of the subcutis with a subcutaneous panniculitis-like pattern [74]. Most patients experience an aggressive clinical course with extranodal and nodal dissemination [74,75].…”

“…Its histological findings are variable and include upper dermal infiltration with marked epidermotropism with ulceration of the epidermis, diffuse dermal infiltration, or involvement of the subcutis with a subcutaneous panniculitis-like pattern [74]. Most patients experience an aggressive clinical course with extranodal and nodal dissemination [74,75]. The identification of primary cutaneous cdTCL was difficult until the TCRc and TCRd antibodies for paraffinsection immunohistochemistry became available commercially.…”