Decrease of 5-hydroxymethylcytosine in primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoproliferative disorder^★

Abstract

Background:

Primary cutaneous CD4⁺ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas.

Objectives:

The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL.

Methods:

Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD.

Results:

Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p<0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4⁺ lymphocytes of PC-SMTLD.

Study limitations:

The small clinical sample size of the study.

Conclusions:

The immunorreactivity of 5-hmC in CD4⁺ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL. © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

KEYWORDS
Cutaneous T-cell lymphoma; DNA methylation; Epigenomics