A 72-year-old man, who had previously been diagnosed with mycosis fungoides (MF) and treated with mogamulizumab, presented for clinical follow-up and was found to have diffuse erythroderma associated with areas of poikiloderma (Fig. 1). A punch biopsy was performed to evaluate for recurrent MF.

Fig. 1
figure 1

A 72-year-old man previously treated for mycosis fungoides has developed diffuse erythroderma

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Histologic sections of the biopsy showed a superficial dermal granulomatous reaction (Fig. 2a–c). Adjacent to the granulomatous reaction were atypical, small to intermediate-sized lymphocytes with irregular nuclei and angulated cytoplasmic borders. These cells were CD3-positive T cells (Fig. 2d) with co-expression of CD4 (Fig. 2e) and GATA3 (Fig. 2g) and no expression of CD7 (Fig. 2f), T-bet (Fig. 2h), or FOXP3 (Fig. 2i).

Fig. 2
figure 2

Histologic sections of the skin biopsy (a-c) show a dermal granuloma and associated atypical small to intermediate-sized lymphocytes. Immunoperoxidase stains indicate the lymphocytes are CD3-positive T cells (d) that are CD4-positive (e), CD7-negative (f), GATA3-positive (g), T-betnegative (h), and mostly FOXP3-negative (i)

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Mogamulizumab is a recently approved humanized anti-CCR4 monoclonal antibody, which causes cytotoxic effects against cells that express CCR4 on their cell membrane, including MF cells and TH2/regulatory T cells. A recent study has shown that patients treated with mogamulizumab can develop a cutaneous granulomatous drug eruption (CGDE) and usually present with erythroderma [1]. Histologically, CGDE can mimic granulomatous MF.

Given the mechanism of this drug, immunohistochemical stains for T-bet, GATA-3, and FOXP3 become useful in discriminating granulomatous MF from mogamulizumab-associated CGDE. T-bet is a T-box transcription factor necessary for the development of TH1 cells. GATA-3 is expressed on TH2 cells, and this T cell type is seen in dermatoses and forms the predominant cell in late stage MF and in patients with erythrodermic MF and Sézary syndrome (SS) [2]. Accordingly, the neoplastic cells in tumor stage MF and SS are GATA-3-positive [3]. FOXP3 is strongly expressed by regulatory T cells and is positive in a significant majority of T cells in most dermatoses [3]. On the other hand, FOXP3-positive T cells comprised less than 10% of the total lymphocytes in the majority of MF biopsies examined in one study and did not exceed 25% in any of the specimens [4].

In the case presented, the atypical lymphoid infiltrate showed a CD3+/CD4+/CD7−/GATA3+/T-bet-/FOXP3-immunophenotype, which supported involvement by MF rather than a drug reaction or other cutaneous inflammatory T cell infiltrate.