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Palmoplantar pustulosis (PPP) is a chronic skin inflammatory disease in which blisters and pustules repeatedly develop on palms and soles. PPP is often refractory to topical therapy, oral therapy, phototherapy, and biologics that are usually applied for PPP. We report a patient with PPP improved by vedolizumab (anti-α4β7 integrin antibody) treatment for ulcerative colitis, suggesting the possibility of a new molecular target for PPP therapy. [ABSTRACT FROM AUTHOR]

Since the cost of molecular biological methods for Spitzoid neoplasms is expensive, the number of institutes that employ these methods might be limited. Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is useful to distinguish melanoma from other melanocytic disorders, including pediatric Spitzoid tumors that are difficult to diagnose by conventional methods alone. In this report, we report a case of PRAME-expressing juvenile Spitzoid melanoma with lymph node metastasis. Unexpectedly, there were few PRAME-expressing cells in the primary tumor, whereas most metastatic tumors expressed PRAME in the metastatic lymph node. These observations might suggest that, in Spitzoid melanomas, a limited number of melanoma cells possess metastatic potential and that metastatic lesions possess clonality. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) significantly prolong survival in patients with metastatic melanoma but can lead to serious immune-related adverse events. In this report, we described a case of atypical neuropathy caused by nivolumab plus ipilimumab combination therapy before primary tumor resection. In our case, not only demyelinating neuropathy, but also muscle weakness and unilateral facial nerve palsy developed and manifested as severe and diverse symptoms. Moreover, unlike spontaneously developing demyelinating peripheral neuropathy, the present case suggested the therapeutic effects of high-dose methylprednisolone monotherapy for the treatment of ICIs-induced immune-related demyelinating peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17. [ABSTRACT FROM AUTHOR]

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolu-mab, ipilimumab plus denosumab combination therapy. [ABSTRACT FROM AUTHOR]

Patients with invasive extramammary Paget's disease have an increased risk of secondary malignancy, mostly occurring colorectal carcinoma. TP53 is a regulator of apoptosis, cell cycle arrest, and DNA damage response pathways, and has been reported as one of the genetic biomarkers for colorectal carcinoma. In this report, we describe a case of advanced invasive EMPD concomitant with cecal cancer with a rare variant of TP53 single nucleotide polymorphism (rs121912665). To our knowledge, there is no English report that presents EMPD concomitant with cecal carcinoma. [ABSTRACT FROM AUTHOR]

Nivolumab plus ipilimumab combined therapy is one of the promising drugs that enhance the anti- immune response in patients with advanced melanoma. Therefore, to increase its response rate is of great interest to dermatologists. Recent reports suggested that, since CD8+ T cells after the administration of ICIs increase the RANKL expression to induce an immunosuppressive tumor microenvironment in melanoma, denosumab might enhance the anti-tumor effects of immune checkpoint inhibitors, such as nivolumab and ipilimumab. In this report, we present a case of multiple metastatic melanoma with nivolumab, ipilimumab plus denosumab combined therapy. [ABSTRACT FROM AUTHOR]

Angioinvasive lymphomatoid papulosis (LyP) type E is a rare variant characterized by angiocentric and angiodestructive features with CD30+ CD8+ lymphocyte infiltration. In rare cases, LyP type E is concomitant with mycosis fungoides, but there is no English report that describe LyP type E developing from parapsoriasis en plaque. In this report, we described a case of angioinvasive LyP (type E) developing from parapsoriasis en plaque, in which we employed immunohistochemical staining for the investigation of its pathomechanisms. [ABSTRACT FROM AUTHOR]

Pigmented breast cancer in the skin caused by nonneoplastic melanocytes of epidermal origin is a rare condition of metastasis from breast cancer, but the pathogenesis of this phenomenon is almost unknown. In this report, we describe a case of breast cancer metastasis in the skin with prominent hyperkeratotic pigmentation caused by nonneoplastic melanocyte colonization. Immunohistochemical staining revealed that the metastatic tumor cells produced IL-23, which is reported not only to induce IL-17 but also to inhibit cell apoptosis in breast cancer cells, which affects tumor progression. In addition to IL-23, substantial numbers of IL-17-producing cells were detected at the peritumoral area, suggesting that IL-17 might induce not only melanogenesis but also keratinocyte proliferation and tumorigenesis. Our report suggests possible mechanisms of hyperkeratotic pigmentation of breast cancer metastasis in the skin. [ABSTRACT FROM AUTHOR]

Keratoacanthoma centrifugum marignatum (KCM) is a rare variant of keratoacanthoma, which is characterized by the dense infiltration of inflammatory cells throughout the dermis, especially around the keratinocytic islands. Therefore, it is sometimes difficult to differentiate between KCM and cutaneous T-cell lymphomas. In this report, we describe a case of KCM with spontaneous regression that showed dense infiltration of CD3+CD8+ T cells. Our present case suggested the importance of investigating tumor-infiltrating lymphocytes to avoid the misdiagnosis of KCM as cutaneous T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be associated with malignant hematological disease, including cutaneous T-cell lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform mycosis fungoides, to select the treatment for CTCL with ichthyosis-like appearance and to evaluate its efficacy is sometimes challenging. In this report, we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise specified presenting AI successfully treated with oral bexarotene. In the present case, the administration of oral bexarotene was not only effective for lymphoma cells infiltrating ulcers and nodules, but it also eliminated AI. [ABSTRACT FROM AUTHOR]

Both long-term administration of immunosuppressive agents and chronic inflammatory conditions, such as autoimmune disease, could be risk factors for the development of cutaneous squamous cell carcinoma (cSCC). In this report, we present a case of recurrent multiple cSCC on the scalp in a patient with juvenile dermatomyositis who had been administered cyclosporine and Predonine since she was a 1-year-old infant. Interestingly, immunohistochemical staining revealed IL-17-producing cells adjacent to IL-17R-expressing atypical keratinocytes. Our present case suggested that IL-17/IL-17R signaling might contribute to the carcinogenesis of cSCC. [ABSTRACT FROM AUTHOR]

Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. [ABSTRACT FROM AUTHOR]

Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30-40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks) followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks), but with severe liver dysfunction. [ABSTRACT FROM AUTHOR]

Since bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis, lupus vulgaris (LV) is reported as one of the rare complications after BCG vaccination, correlating with immunosuppression in the lesional skin. In this report, we describe a case of LV arising from the BCG vaccination site 22 years after vaccination. Interestingly, in the present case, granuloma cells were composed of M2-polarized macrophages. Our case might explain the contribution of M2-polarized macrophages to the biology of LV arising from a BCG vaccination site. [ABSTRACT FROM AUTHOR]

Ectopic extramammary Paget's disease (EMPD) is a rare variant of EMPD that develops in nonapocrine regions. Since reports about ectopic EMPD are limited, little is known about the biological and immunological background of ectopic EMPD. In this report, we present a case of ectopic EMPD on the lower abdomen that expressed RANKL but lacked the expression of MMP7. As we previously reported, Paget's cells express RANKL and MMP7, release soluble RANKL in the tumor microenvironment, and stimulate tumor-associated macrophages to produce tumor-loading factors in conventional EMPD. In our present case, both CCL5-expressing cells and MMP25-bearing cells were lacking, whereas substantial numbers of CCL5-expressing cells and MMP25-bearing cells were found in conventional EMPD. Our case suggested that the lack of MMP7 on Paget's cells might be one of the possible explanations for the biology of ectopic EMPD. [ABSTRACT FROM AUTHOR]

Background: Minigrafts using a 1-mm biopsy punch (1-mm minigrafts) are being increasingly used to treat vitiligo. However, there have been few reports of the use of 1-mm minigrafts in pediatric patients.Objective: To examine the effectiveness of combination therapy with 1-mm minigrafts and phototherapy in children with segmental vitiligo.Methods: Minigrafts were placed in 13 patients aged ≤16 years with segmental vitiligo. Following surgery, 11 patients underwent irradiation with excimer laser light and 2 with narrow-band ultraviolet B light.Results: A mean repigmentation of 81.6% was obtained. A particularly high mean repigmentation of 87.9% was seen in patients aged ≤12 years, indicating greater efficacy in these patients than in patients aged ≥13 years (mean, 67.5%). Although a transient cobblestone appearance occurred as an adverse effect, it improved over time.Conclusions: Combined treatment of segmental vitiligo with 1-mm minigrafts and phototherapy can be performed safely and is highly effective in young patients. [ABSTRACT FROM AUTHOR]

Plexiform fibrohistiocytic tumor (PFT) is a rare mesenchymal neoplasm of intermediate malignant potential with a high local recurrence rate. In this report, we describe a case of PFT on the ear, which showed a dense deposition of periostin (POSTN) in the stromal areas of the tumor. In addition, dense infiltration of CD163+CD206- tumor-associated macrophages (TAMs) was detected in the same areas as POSTN. Since POSTN was previously reported to possess immunomodulatory effects on TAMs, our present report suggested the significance of the POSTN/TAMs axis in the progression of PFT. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma that only rarely regresses spontaneously. Since little is known about the immunological mechanisms involved in the spontaneous regression of MCC, we describe a case of MCC with spontaneous regression and employed immunohistochemical staining for cytotoxic and immunosuppressive molecules to investigate possible mechanisms involved in the spontaneous regression of MCC. Interestingly, compared to conventional MCC, tumor-infiltrating lymphocytes in MCC with spontaneous regression contained higher numbers of CD8+ cells and granulysin-bearing cells and lower numbers of CD206+ cells. Our present study suggests one of the possible reasons for the spontaneous regression of MCC. [ABSTRACT FROM AUTHOR]

Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of mycosis fungoides limited to the palms and soles. Although little is known about the pathogenesis of MFPP, this variant of mycosis fungoides presents a relatively good prognosis. In this report, we describe an 85- year-old Japanese man with MFPP. Immunohistochemical staining revealed the dense deposition of periostin in the cancer stroma, as well as infiltration of CD163+CD206- tumorassociated macrophages (TAMs), which suggested the phenotypes of TAMs were not polarized to the M2 phenotype in the lesional skin of MFPP. Our present case might suggest one of the possible reasons for the good prognosis of MFPP. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is characterized by the clonal proliferation of Langerhans cells; it is categorized as a single-system disease with single or multifocal lesions, and as a multi-system disease with or without the risk of organ involvement. Although the skin is not categorized as a risk organ, the precise diagnosis of skin lesions is necessary to determine the protocol for the treatment of LCH. In this report, we describe a 28-year-old Japanese man with adult onset of BRAFV600E-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAFV600E gene could be a diagnostic tool to determine the clinical type of LCH. © 2015 The Author(s). Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abatacept is a biological immune modifier that is used for the treatment of rheumatoid arthritis. Although psoriasiform drug eruption is reported as one of the cutaneous adverse effects of abatacept, the precise mechanisms are not fully understood. In this report, we describe a 65-year-old Japanese man with psoriasiform drug eruption caused by abatacept. Interestingly, immunohistochemical staining revealed that the epidermal keratinocytes in the basal layer and lower layers of the stratum spinosum were positive for pSTAT3, partially positive for pSTAT1 and negative for pSTAT6, which is similar to conventional psoriasis vulgaris. Our present study suggests that psoriasiform drug eruption caused by abatacept might develop by similar immunological mechanisms as those of psoriasis vulgaris. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for cutaneous squamous cell carcinoma (SCC) on cosmetic areas. Although this reagent is useful for the treatment of SCC, its immunomodulatory effect on the tumor microenvironment is still unknown. Objective/Methods: In this study, we investigated the immunomodulatory effects of PEP on the tumor-infiltrating regulatory T cells and tumor-associated macrophages as well as CD8+TIA-1+ cytotoxic T cells in the lesional skin of 5 patients with SCC on the lips. Results: Our data suggest that, in addition to the direct antitumor effects, PEP decreased immunosuppressive cells and increased cytotoxic T lymphocytes at the tumor sites, which might maintain antitumor immune response against SCC. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: M2 macrophages play a critical role in the induction of T helper 2 (Th2) polarization.Methods: To investigate the contribution of M2 macrophages to the pathogenesis of bullous pemphigoid (BP) and pemphigus vulgaris (PV), we employed immunohistochemical staining for CD163 and CD206, as well as pSTAT1, pSTAT6, interleukin (IL)-4, IL-13, CCL17, CCL18 and Foxp3 in the lesional skin of 10 cases of BP and PV.Results: The numbers of CD163+ CD206+ M2 macrophages were higher in BP than in PV. Moreover, pSTAT6+ cells, CCL17+ cells, CCL18+ cells and Foxp3+ regulatory T cells were prominent only in the lesional skin of BP. To further investigate the function of M2 macrophages, we examined the mRNA expression and production of Th2-related chemokines from M2 macrophages in vitro, which showed a significant increase in the mRNA expression and production of CCL18 when stimulated by IL-4 or IL-13.Conclusion: Our study sheds light onto one of the possible immunological mechanisms of BP and PV. [ABSTRACT FROM AUTHOR]

An imbalance of immunosuppressive and cytotoxic cells plays an important role in inhibiting the anti-tumor immune response of the tumor-bearing host. The purpose of this study was to elucidate the involvement of immunosuppressive cells, such as regulatory T cells and CD163+ M2 macrophages as well as cytotoxic cells, such as granulysin-bearing cells and TIA-1+ cells in cutaneous angiosarcoma (AS) by immunohistochemical staining. In addition we evaluated the potencies of bisphosphonate, which was previously reported to suppress the expression of matrix metalloproteinase 9 (MMP-9), as a supportive therapy for AS together with docetaxel in 6 cases of cutaneous AS. These findings suggest that a high number of immunosuppressive cells might be related to the prognosis of AS, and that a combination of docetaxel with bisphosphonate risedronate sodium might be effective for MMP-9-expressing AS. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

T helper 17 cells, characterized by interleukin-17 (IL-17) production, play a critical role in the pathogenesis of autoimmune disease, including alopecia areata (AA). In this report, we employed immunohistochemical staining for IL-17-producing cells, as well as interferon-γ-producing cells, granulysin-bearing cells and Foxp3+ regulatory T cells, and performed a quantitative analysis of IL-17-producing cells in the lesional skin of several clinical forms of AA by TissueFAXS analysis. Among them, interestingly, the ratio of IL-17-producing cells in acute, diffuse and total alopecia was significantly lower than those of multiple types of AA. Our study sheds light on one of the possible immunological mechanisms of AA. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Erythema papulatum centrifugum (EPC) was first described in 1962 by Watanabe [Jpn J Dermatol 1962;72:573] as eczematous lesions extending centrifugally. To date, more than 150 cases have been reported, but only in the Japanese literature. A review of the Japanese literature including our 5 new cases reveals that EPC occurs in middle-aged persons, predominantly in males, as a single lesion on the trunk that is self-limiting but recurs frequently. Although EPC shares several characteristics with the superficial type of erythema annulare centrifugum or asymmetrical periflexural exanthema, EPC differs from erythema annulare centrifugum in clinical manifestation, showing annular rings composed of grouped, tiny papules, and in the histology of perieccrine inflammation, while it differs from asymmetrical periflexural exanthema by male preponderance, onset age, high relapse rate and unique annular configuration. We discuss EPC as compared with other cutaneous disorders showing annular erythema or similar histopathology and suggest that EPC is a distinct clinical entity. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]