TOX expression in cutaneous B-cell lymphomas.

Anne M R Schrader,Patty M Jansen,Rein Willemze

doi:10.1007/s00403-016-1654-7

Abstract

Thymocyte selection-associated high-mobility group box (TOX) is aberrantly expressed in cutaneous T-cell lymphomas. In a recent study, TOX expression was noted unexpectedly in the follicle center (germinal center) B-cells of reactive lymph nodes and tonsils, used as external controls. To evaluate whether TOX is also expressed by cutaneous B-cell lymphomas, TOX immunohistochemistry was performed on skin biopsies of 44 patients with primary and secondary cutaneous B-cell proliferations. TOX was expressed not only in the reactive follicle center cells of lymph nodes, tonsils, cutaneous lymphoid hyperplasia, and primary cutaneous marginal zone lymphomas, but also by the neoplastic follicle center cells of 16/17 patients with primary cutaneous follicle center lymphoma (PCFCL) and 7/7 patients with cutaneous manifestations of systemic follicular lymphoma (FL). Notably, TOX showed a very similar expression pattern as BCL6, a marker of germinal center B-cells. In 4/10 patients with a BCL6+ primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT) and in 2/2 patients with a secondary cutaneous BCL6+ diffuse large B-cell lymphoma (DLBCL), TOX was expressed by more than 50 % of the neoplastic B-cells. In contrast, in 3/3 BCL6− PCDLBCL,LT, TOX was completely negative or weakly expressed by a minor proportion of the neoplastic B-cells. In conclusion, TOX is expressed not only by neoplastic T-cells, but also by both reactive and neoplastic follicle center (germinal center) B-cells and a proportion of BCL6+ PCDLBCL,LT and secondary cutaneous BCL6+ DLBCL. The functional significance of TOX expression in reactive and neoplastic B-cells remains to be elucidated.

Highlights

In the past few years, Thymocyte selection-associated high-mobility group box (TOX) [thymocyte selection-associated high-mobility group (HMG) box] has been described as a potential new diagnostic marker for cutaneous T-cell lymphoma (CTCL) [16]
In the reactive lymph nodes and tonsils that were used as benign external controls, TOX was expressed in the follicular areas and by scattered small lymphocytes, probably T-cells, in the interfollicular areas (Fig. 1)
TOX was expressed by the neoplastic follicle center cells in 16/17 patients (94 %) with primary cutaneous follicle center lymphoma (PCFCL) and in 7/7 patients (100 %) with skin lesions of systemic follicular lymphoma (FL) (Fig. 2)

Summary

Introduction

In the past few years, TOX [thymocyte selection-associated high-mobility group (HMG) box] has been described as a potential new diagnostic marker for cutaneous T-cell lymphoma (CTCL) [16]. TOX is a family member of HMG box proteins and is involved in the regulation of gene expression, as by modifying the density of the chromatine structure [13]. TOX is associated with the development of CD4? TOX was shown to be expressed in the development of other lymphoid cells, such as lymphoid tissue inducer (LTi) cells that normally act as key regulators of lymph node organogenesis [2]. Recent studies showed aberrant expression of TOX in different types of CTCL, mainly Sezary syndrome (SS) and mycosis fungoides (MF), and in primary cutaneous CD30? Morimura et al suggested that TOX expression is limited

Methods

Results

Conclusion