In tumor immunity, the participation of IL-10eproducing regulatory B cells (Bregs), which play an important role in suppressing immune responses, is unclear. In this study, we demonstrated an increase in B16F10 melanoma growth and a decrease in the proportion of IFN-ge and TNF-aesecreting tumor-infiltrating CD8 þ T cells in B cellespecific PTEN-deficient mice in which Bregs were expanded. The number of tumor-infiltrating Bregs significantly increased in B cellespecific PTEN-deficient mice. More than 50% of tumor-infiltrating B cells consisted of Bregs, predominantly CD19 þ CD5 þ CD43 þ B1a Bregs, in both B cellespecific PTEN-deficient and control mice. Adoptive B1a B cell transfer, which includes >30% of Bregs, increased melanoma growth, whereas non-B1a B cell transfer, which includes <2% of Bregs, exhibited no effect. In addition, adoptive transfer of B1a B cells from wild-type mice, but not IL-10 e/e mice, exacerbated B16F10 melanoma growth. The current study indicates that B1a Bregs negatively regulate anti-melanoma immunity by producing IL-10 and reducing T helper 1 type cytokine production in tumor-infiltrating CD8 þ T cells. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.

Objective To investigate the role of adhesion molecules in C protein-induced myositis (CIM), a murine model for polymyositis (PM). Methods CIM was induced in wild type mice, L-selectin-deficient (L-selectin-/-) mice, ICAM-1-deficient (ICAM-1-/-) mice, and both L-selectin- and ICAM-1-deficient (L-selectin-/-ICAM-1-/-) mice. The severity of myositis, inflammatory cell infiltration, and mRNA expression in the inflamed muscles were examined. The effect of dendritic polyglycerol sulfate (dPGS), a synthetic inhibitor that suppresses the function of L-selectin and endothelial P-selectin, was also examined. Results L-selectin-/- mice and L-selectin-/-ICAM-1-/- mice developed significantly less severe myositis compared to wild type mice, while ICAM-1 deficiency did not inhibit the development of myositis. L-selectin-/- mice transferred with wild type T cells developed myositis. Wild type mice treated with dPGS significantly diminished the severity of myositis compared to control-treated wild type mice. Conclusions These data indicate that L-selectin plays a major role in the development of CIM, whereas ICAM-1 plays a lesser, if any, role in the development of CIM. L-selectin-targeted therapy may be a candidate for the treatment of PM.

Abstract:Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present.

Objective To assess the longitudinal changes in nailfold videocapillaroscopy (NVC) in patients expressing myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetase [ARS], anti-transcriptional intermediary factor 1 [TIF1], and anti-melanoma differentiation-associated gene 5 [MDA5]). Methods This study was performed retrospectively, at a single site, on an observational cohort. Seventy-one idiopathic inflammatory myopathy patients were included (25 patients expressed anti-MDA5 Abs, 24 patients expressed anti-TIF1 Abs, and 22 patients expressed anti-ARS Abs). NVC findings included giant, enlarged, and reduced capillaries, hemorrhages, capillary ramification, disorganization of the vascular array, and capillary loss. NVC findings were compared from baseline to after disease activity stabilization. Results The frequency of enlarged capillaries at baseline was different among the three groups, and was significantly higher in patients with anti-TIF1 Abs compared with those with anti-ARS Abs (88% vs 55%, p&lt; 0.05). Reduced capillaries were significantly increased in patients with anti-TIF1 Abs compared with those with anti-MDA5 (96% vs 44%, p&lt; 0.0001) or anti-ARS Abs (96% vs 50%, p&lt; 0.0005). Both enlarged and reduced capillaries improved after stabilization in patients with anti-MDA5 Abs (p&lt; 0.0001 and p&lt; 0.05, respectively). These improvements were not observed in patients expressing anti-TIF1 and anti-ARS Abs. However, a significant reduction in hemorrhages was observed in all three groups (p&lt; 0.0001 for each group). Conclusions The results of this study demonstrate that longitudinal changes in NVC findings may vary depending on myositis-specific Ab expression. Therefore, it is crucial to assess individual NVC findings separately, since each finding may impact disease activity in a different manner.

A 10-year-old Japanese girl presented with a rhomboid-shaped brown macule, 4x3 mm in size, on the sole of the right foot. Dermoscopic examination revealed a number of black dots and globules on the ridges of the skin, marking an area of symmetrical brown pigmentation. On the periphery, a streak-like arrangement of black dots/globules on the brown pigmentation was observed along the ridges, simulating a “starburst” pattern. The lesion was excised and histological examination showed a symmetrical wedge-shaped compound melanocytic lesion that consisted of junctional and intradermal nests of a mixture of large spindle and epithelioid cells. None of the cells were atypical, and maturation of the cells with increasing depth was observed. From these findings, a diagnosis of Spitz nevus was made. Transepidermal elimination of nevus cell nests was observed and there were small groups of degenerated melanin-laden cells in the cornified layer. Masson Fontana stain revealed fine melanin deposits in the nevus cells of the junctional and intradermal nests, as well as heavy melanin deposits in the small groups of degenerated cells in the cornified layer. The distribution of melanin may contribute to a unique dermoscopic finding in this case.