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Dear Editor,We previously established human induced pluripotent stem (iPS) cell-derived melanocytes in large quantities within a short period and induced their differentiation and high melanogenic potency using original iPS cell-derived melanocyte medium (iDMM). 1 We used original iPS cell lines established from T cells in the blood of a healthy 40-year-old Japanese man and a Sendai virus vector. 1 In the present study, we established melanocytes derived from more general iPS cells (1383D6, HPS1006) obtained from the Japanese Center for iPS Cell Research and Application using advanced iDMM (Table S1). The iPS cells were maintained in StemFit medium (AHS, AK02N; Ajinomoto, Tokyo, Japan). We found that many pigmented cells developed from the border of human iPS cell nests within 10 days under advanced iDMM (Fig. 1a). The granules in them were strongly tyrosinase-positive as observed by confocal immunofluorescence laser microscopy, which suggested that they were mature melanocytes (Fig. 1b). Previous approaches to grow and differentiate iPS cells into melanocytes needed first to produce embryoid bodies and then to process them to differentiate into melanocytes, which took approximately 30 days. 2,3 The present approach further improves in production of large quantities within a short period and induces differentiation and high melanogenic potency in vitro. We examined the mRNA expression levels of NANOG, Pax3, MITF, TRP1 and tyrosinase in the human iPS cell-derived melanocytes using quantitative reverse transcription polymerase chain reaction (Table S2, Fig. 1c). Normal human adult epidermal melanocytes were purchased from Invitrogen Gibco (Carlsbad, CA, USA) as controls (Table S3).The mRNA expression level of the pluripotency marker NANOG in these iPS cell-derived melanocytes was significantly lower than in human iPS cells. In contrast, mRNA expression levels of four melanocyte-specific markers (Pax3, MITF, TRP1 and tyrosinase) in the iPS cell-derived melanocytes that we established from a line of human melanocytes were significantly higher than in human iPS cells. The melanocyte-specific marker mRNA expression levels in the iPS cell-derived melanocytes were similar to the levels found in normal human adult epidermal melanocytes (Table S4).

Merkel cell carcinoma (MCC) is an aggressive, cutaneous, neuroendocrine carcinoma and, in rare cases, occurs with Bowen's disease (BD). In this report, we describe a case of MCC concurrent with invasive BD and compare the profiles of tumor-infiltrating leukocytes in the lesional skin of MCC and invasive BD. Interestingly, immunohistochemical study revealed significant numbers of CD8+ cells and caspase 3-expressing cells in the same areas of invasive BD and MCC. Our present case suggests that MCC concurrent with invasive BD might have a good prognosis because of the substantial number of CD8+ cells in the tumor.

We propose that the positive pressure and physical impairment under the contact area of the face mask could trigger external dental fistulas associated with apical periodontitis in the present case. We propose that patients who undergo noninvasive positive pressure ventilation should maintain appropriate oral hygiene to avoid apical periodontitis and the subsequent risk of external dental fistula.

a b s t r a c tAngiosarcoma (AS) is a highly aggressive vascular tumor that spreads widely throughout the skin. Since AS tends to recur locally and metastasize early, an additional intensive therapy is necessary. In this report, we describe an 83-year-old man with recurrent AS that metastasized to the right external auditory meatus, who achieved complete remission with CyberKnife and weekly administration of bisphosphonate risedronate sodium. Results of the present study might suggest the novel possibility of using CyberKnife with weekly administration of bisphosphonate risedronate sodium for the treatment of inoperable metastatic AS.