TOX expression in cutaneous T-cell lymphomas: an adjunctive diagnostic marker that is not tumour specific and not restricted to the CD4+ CD8- phenotype

Background TOX (thymocyte selection-associated high-mobility group box) was shown to be aberrantly expressed in mycosis fungoides (MF) and Sezary syndrome (SS) and is suggested to have additional diagnostic value. However, data on expression in other types of cutaneous T-cell lymphoma (CTCL) are scarce and it is unknown whether TOX is expressed only by MF with a CD4(+) CD8(-) phenotype. Objectives To investigate TOX expression in various types of CTCL with different T-cell phenotypes. Methods Immunohistochemical expression of TOX was evaluated on 153 skin biopsies of 132 patients with CTCL and 60 patients with benign inflammatory dermatoses (BIDs). Results TOX was expressed by > 50% of the neoplastic T cells in 49 of 59 patients (83%) with MF and in 19 of 22 patients (86%) with SS. The TOX+ cases of MF included 34 of 35 cases (97%) with a CD4(+) CD8(-) phenotype, but also five of eight cases (63%) with a CD4(-) CD8(+) phenotype and 10 of 16 cases (63%) with a CD4(-) CD8(-) phenotype. TOX expression in other types of CTCL was common but showed variable intensity. Although only one of 60 patients (2%) with a BID expressed TOX in > 50% of the skin-infiltrating T cells, some caution is warranted, as the majority of BIDs had TOX+ T cells varying between 11% and 50%. Conclusions TOX expression is not tumour specific, is not restricted to CTCL with a CD4(+) CD8(-) phenotype, and, on its own, is insufficient for diagnosis of CTCL. However, it may have an adjunctive diagnostic role in conjunction with other clinical and histological data.