br Conclusion br Introduction Hypopigmented mycosis fungoide

Conclusion
Introduction Hypopigmented mycosis fungoides (HMF) is described as a clinical variant of MF presenting a good prognosis, but the condition is not clearly defined by the World Health Organization or the European Organization for Research and Treatment of Cancer classification of cutaneous lymphoma. Recently, Boulos et al reported a case series of 34 patients with juvenile-onset mycosis fungoides, which suggested that 53% of juvenile-onset MF is a hypopigmented type, and about 40% of them contained CD8+ immunophenotypes. Notably, the infiltration of CD8 determines the prognosis of several types of lymphomas, which suggested possible reasons for the good prognosis of HMF. Regulatory T cells (Tregs) are classically identified by the expression of CD4, CD25, and Foxp3. Tregs induce immunological tolerance in cancer patients by a variety of mechanisms together with other suppressor cells. For instance, depletion of CD4+CD25+ Tregs enhances the immune responses against tumor keap1-nrf2 pathway to induce an antitumor immune response in melanoma patients. In the dermatopathological field, we previously reported significant difference in Tregs between invasive and noninvasive skin tumors, such as extramammary Paget\'s disease (EMPD), squamous-cell carcinoma, and Bowen disease. These reports suggested that the ratio of Tregs could be connected with the cancer progression in skin tumors. In this report, we describe a case of HMF, and investigate the profiles of tumor-infiltrating leukocytes (TILs) in the lesional skin of this patient.
Case Report A 22-year-old Japanese woman visited our outpatient clinic with an 11-year history of multiple vitiligo. She had been treated with topical 0.1% tacrolimus for 9 years for vitiligo vulgaris in another clinic. On her initial visit, physical examination revealed multiple vitiligo with central faint erythema on the lateral side of her trunk and lower limbs (Figure 1A). A biopsy specimen showed that atypical large lymphocytes densely infiltrated mainly the upper dermis region with involvement of the overlying epidermis (Figure 1B). Immunohistochemical staining revealed that these atypical lymphocytes, which were distributed from the upper layer of stratum spinosum to the dermis, were negative for CD4 (Figure 1C) and CD7 (Figure 1D), and positive for CD3, CD5, and CD8 (Figure 1E). There were few CD161+ cells in the dermis. To further confirm the profiles of TILs in MF, we employed double staining for CD8 with granulysin (Figure 2A) or CD8 with CD7 (Figure 2B), which revealed that CD8+granulysin+ cells and CD8+CD7+ cells were distributed at the basal layers of the epidermis and the dermis, whereas CD8+CD7– cells and CD8+ granulysin– cells were distributed from the upper layer of stratum spinosum to the dermis. Substantial numbers of T-cell intracellular antigen-1 (TIA-1)+ cells were also detected in the area of distribution of TILs (data not shown). The double staining of Foxp3 with CD4, CD8, or CD25 revealed that substantial numbers of CD4+Foxp3+ cells and CD25+Foxp3+ cells were detected in the dermis (Figure 2C). There is no CD8+Foxp3+ cell in the lesional skin of HMF, as we previously reported (data not shown). The percentage of Foxp3+ cells was 18.4% ± 6.7% and 16.7% ± 6.3% among CD4+ cells and CD25 cells, respectively. We summarized the ratio of Foxp3+ cells in our case and compared it with the five cases of conventional MF, five cases of noninvasive EMPD, and invasive EMPD cases, as we previously reported (Figure S1). We treated our patient with narrow-band UVB five times a week for 4 weeks; most lesions, however, repigmented 2 months after the treatment.
Discussion HMF is described as a juvenile type of MF that has a relatively good prognosis compared with conventional MF. Although the prognosis of HMF is relatively good, and the profiles of TILs determine the prognosis of cutaneous T-cell lymphoma (CTCL), the precise immunological profiles of HMF have not been reported yet. Therefore, in this report, we shed light on the profiles of T cells infiltrating around the tumor cells, particularly focusing on Tregs and cytotoxic molecules.