Loss of expression of 5-hydroxymethylcytosine in CD30-positive cutaneous lymphoproliferative disorders

Background The 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, no studies have analyzed this epigenetic marker in cutaneous lymphomas. Therefore, we aimed to analyze the expression of 5‐hmC in cutaneous CD30‐positive lymphoproliferative disorders and compare it with a control group composed of reactive infectious and inflammatory disorders with CD30‐positive cells. Methods Retrospective case series study with immunohistochemical analysis using anti‐CD30 and anti‐5‐hmC antibodies in control (n = 19), lymphomatoid papulosis (LyP) (n = 27) and primary cutaneous anaplastic large cell lymphoma (ALCL) (n = 14) specimens. Results Complete loss of 5‐hmC nuclear staining by CD30+ cells was observed in 63% of LyP cases, 57% of ALCL cases and 0% of control cases. Conclusions The presence of 5‐hmC+ and CD30+ lymphocytes was highly suggestive of a benign process. In contrast, loss of 5‐hmC nuclear staining was highly suggestive of a lymphoproliferative disorder (ALCL or LyP). Under these circumstances, the use of 5‐hmC staining can be a useful adjunctive tool for discriminating between neoplastic CD30+ lymphoproliferations and inflammatory/infectious simulators harboring reactive CD30+ cells.