In this report, we employed immunohistochemical staining to verify the TILs with special focus on the profiles of T cell subsets and the tumor stroma.

Next, to evaluate the tumor-composing cells in the cutaneous lymphadenoma, we performed immunohistochemical stainings, which revealed that these mononuclear cells within the lobules and tumor stroma areas were mainly CD1a⁺ cells (fig. ​fig.3a3a) and, CD3⁺, CD4⁺, CD7⁺, CD8⁺ and TIA-1⁺ T cells (fig. 3b–e, h). These tumor-infiltrating T cells were mainly CD45Ro⁺ memory T cells, and several CD45RA⁺ cells were also detected (data not shown). In addition, several Foxp3⁺ Tregs were detected within the lobules (fig. ​fig.44). CD20⁺ cells and CD68⁺ cells were also detected within and around the lobules (fig. 3f, g). CD56⁺ cells were not detected in our case (data not shown).

Previously, several reports suggested that, in cutaneous lymphadenoma, cells within both the lobules and interstitial area consist of CD1a⁺ Langerhans cells, CD30⁺ T or B cells, and CD3⁺ T cells [1, 4]. More detailed investigation has not been performed yet. In our case, immunohistochemical staining for CD3, CD4, CD8, TIA-1, CD20, CD68, Foxp3 and CD56 was found in the phenotypic analysis of the cutaneous lymphadenoma-infiltrating cells. We investigated the expression of CD45RA and CD45Ro on infiltrating lymphocytes, and found that, in cutaneous lymphadenoma, infiltrating cells mainly consist of memory T cells. We also detected prominent infiltration of Foxp3⁺ Treg cells, as we previously reported in other types of skin tumors [9]. In addition, we also focused on the tumor stroma. In our case, the tumor lobules consisted of AE1/AE3⁺ and BerEP4⁺ cells, and within the lobules, stroma is mainly positive for AE1/AE3. In contrast, on the outside of the lobules, the stroma showed abundant mucin deposits. As we previously reported the profiles of TILs in metastatic malignant melanomas [10], normally in malignant tumor microenvironment, specific lymphocytes such as Tregs, cytotoxic T lymphocytes, etc. are increasing. In the present case, there is no tendency of increasing numbers of effector T cells, suppressor cells, nor antigen-presenting cells. These observations may be because cutaneous lymphadenoma is not a malignant tumor but a benign neoplasm of follicular or lymphoepithelial differentiation. Our present case suggested that the pathogenesis of tumor-infiltrating cells in cutaneous lymphadenoma is different from TILs in malignant skin tumors. Though we could not further assess the functions of these infiltrating cells, our present study suggests, at least, that these varieties of lymphocytes may have played roles in tuning and maintaining the homeostasis of this tumor.