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. 2018 Oct;73(4):653-662.
doi: 10.1111/his.13671. Epub 2018 Jul 27.

T-cell receptor-δ expression and γδ+ T-cell infiltrates in primary cutaneous γδ T-cell lymphoma and other cutaneous T-cell lymphoproliferative disorders

Affiliations

T-cell receptor-δ expression and γδ+ T-cell infiltrates in primary cutaneous γδ T-cell lymphoma and other cutaneous T-cell lymphoproliferative disorders

Melissa Pulitzer et al. Histopathology. 2018 Oct.

Abstract

Aims: The diagnosis of cutaneous γδ T-cell lymphoma (GDTCL) requires the identification of γδ chains of the T-cell receptor (TCR). Our aim in this study was, by using a new monoclonal antibody (mAb) against TCRδ, to evaluate TCRδ expression in formalin-fixed paraffin-embedded (FFPE) skin tissue from TCRγ+ cutaneous T-cell lymphoma (CTCL), and to assess TCRδ expression within a spectrum of other cutaneous lymphoproliferative disorders (CLPDs).

Methods and results: Twelve cases (10 patients) with TCRγ+ CTCL and 132 additional CLPD cases (127 patients) were examined, including mycosis fungoides (MF) (n = 60), cutaneous GDTCL (n = 15), subcutaneous panniculitis-like T-cell lymphoma (SPTCL) (n = 11), and CD30+ lymphoproliferative disorder (LPD) (n = 24). Clone H-41 against TCRδ was used on a Leica Bond-3 automated stainer to label FFPE slides. H-41 immunostaining was graded as percentage infiltrate: high (50-100%), moderate (10-49%), and low (0-9%). In TCRγ+ tumours, 12 of 12 (100%) patients showed TCRδ expression comparable to TCRγ expression. No (0%) TCRγ+ cases were negative for TCRδ. In all CLPDs, TCRδ expression was as follows: GDTCL, 16 of 20 cases (14 of 15 patients) high, two moderate, and two low; MF, 0 of 60 cases high, nine moderate, and 51 low; CD30+ LPD, one of 24 cases high, two moderate, and 21 low; and SPTCL, 0 of 11 cases (0 of 9 patients) high, two moderate, and two low. Three MF-like cases and one SPTCL-like case showed high expression; the remainder showed low expression.

Conclusions: mAb H-41 against TCRδ matches TCRγ in immunostaining FFPE tissues from GDTCL, supporting H-41 as a replacement for mAb γ3.20. TCRδ expression in our study suggests that the true occurrence of γδ+ non-GDTCL CTCL/CLPD may be lower than suggested by the recent literature.

Keywords: T-cell lymphoma; classification; immunohistochemistry; immunological techniques; lymphoproliferative disorders.

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Conflict of interest statement

A conflict of interest statement:

SH has consulting relationships with Celgene Millenium/Takeda Kyowa-Hakka-Kirin Seattle Genetics Forty-Seven Mundipharma Verastem, and research relationship with Celgene Millenium/Takeda Kyowa-Hakka-Kirin Seattle Genetics Forty-Seven Infinity/Verastem Spectrum Pharmaceuticals, ADCT Therapeutics and Aileron Therapeutics. AM consulting relationships with Seattle Genetics and BMS. MP, SG, DF, PM, MK, AC, AD and AJ have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Primary cutaneous gamma-delta T-cell lymphoma; A, B hematoxylin and eosin stain. C shows TCRδ immunohistochemistry, D shows TCRβ and TCRγ immunohistochemistry.
Figure 2
Figure 2
TCRγδ expression in a borderline primary cutaneous CD30+ lymphoproliferative disorder: A, B, Hematoxylin and eosin; C, 80% TCRδ in dermis; D, Immunohistochemistry for CD30 in dermal population.
Figure 3
Figure 3
Examples of primary cutaneous T-cell lymphomas with clinical behavior of mycosis fungoides or subcutaneous panniculitis like T-cell lymphoma, and prominent TCRγδ phenotype as shown by TCRδ immunohistochemistry. A–D, hematoxylin-eosin, TCRβ, TCRδ, and clinical patch lesions in a patient with a mycosis fungoides presentation and 84 months of follow-up; E–G, hematoxylin-eosin, TCRβ, and TCRδ in a recently diagnosed patient with a mycosis fungoides-like presentation; H–K hematoxylin-eosin, TCRβ, TCRδ, and clinical subcutaneous nodule in a panniculitic patient with indolent course through limited (several month) follow up; L–N, hematoxylin-eosin, TCRβ, and TCRδ in a panniculitic presentation with indolent course through 84 months.
Figure 4
Figure 4
Two patients with primary cutaneous T-cell lymphoma, retrospectively classified as gamma-delta T-cell lymphoma upon review of their clinical history, after tissue evaluation with TCRδ immunohistochemistry. A–D hematoxylin and eosin, TCRβ, TCRδ and clinical images illustrating a large facial tumor in the absence of patches or plaques. E–H, hematoxylin and eosin, TCRβ, TCRδ and clinical image showing a large ulceration in the absence of patches or plaques.

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