Sung-Eun Chang

Opposing roles for calcineurin and ATF3 in squamous skin cancer.

Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients. Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65 to 100-fold higher risk than in the normal population. By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent. Here we report that genetic and pharmacological suppression of calcineurin/nuclear factor of activated T cells (NFAT) function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-rasV12 (also known as Hras1)-expressing primary human keratinocytes or keratinocyte-derived SCC cells. Calcineurin/NFAT inhibition counteracts p53 (also known as TRP53)-dependent cancer cell senescence, thereby increasing tumorigenic potential. ATF3, a member of the ‘enlarged’ AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumorigenic potential. Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients. Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65–100 fold higher risk than in the normal population1. By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent 1. Here we report that genetic and pharmacological suppression of calcineurin/NFAT function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-rasV12 expressing primary human keratinocytes or keratinocyte-derived SCC cells. Calcineurin/NFAT inhibition counteracts p53-dependent cancer cell senescence thereby increasing tumourigenic potential. ATF3, a member of the “enlarged” AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumourigenic potential. Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.

Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib

Summary Background  The multitargeted kinase inhibitors sorafenib and sunitinib have improved treatment of solid tumours including renal cell carcinoma and hepatocellular carcinoma by offering better clinical responses. However, sorafenib and sunitinib are commonly associated with cutaneous toxicity.

Neuropeptides and their receptors in psoriatic skin in relation to pruritus

Background  Pruritus in patients with psoriasis has been reported to be more common than previously thought.

Primary adenoid cystic carcinoma of skin with lung metastasis

Primary cutaneous adenoid cystic carcinoma was first reported in 1975. We report a case of this malignancy with pulmonary metastases in a 70-year-old man and offer a brief review of the literature.

Clinicopathological features of CD56+ nasal‐type T/natural killer cell lymphomas with lobular panniculitis

Nasal‐type T/natural killer cell lymphoma (TNKCL) shows frequent extranodal involvement including the skin, and is associated with a poor prognosis. We have studied six patients with nasal‐type TNKCL presenting with inflammatory subcutaneous nodular lesions with a subcutaneous lymphoid infiltrate. Clinical information was obtained from the medical records of the patients and at follow‐up. All cases showed features of angiocentric lymphoma on histology, although there was diffuse cellular infiltration rather than an angiocentric pattern in the subcutis. All six patients were similar in immunophenotype: positive for CD56 and either cytoplasmic CD3 or CD45RO, but negative for B‐cell markers and CD30. In situ hybridization using an anti‐sense Epstein–Barr virus early regions probe showed a positive reaction in all cases. All patients either died with progressive disease or showed no response to combined chemotherapy. The diagnosis of nasal‐type TNKCL, which has a fatal outcome, is facilitated by detection of CD56‐positive tumour cells. In evaluating lobular panniculitis including apparently benign inflammatory subcutaneous nodules, nasal‐type TNKCL should be considered in the differential diagnosis, especially in Asian countries.

Histopathological study of the treatment of melasma lesions using a low-fluence Q-switched 1064-nm neodymium:yttrium-aluminium-garnet laser.

The low‐fluence 1064‐nm Q‐switched neodymium:yttrium–aluminium–garnet (QSNY) laser is a widely used treatment for melasma in East Asia, although its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of action of the QSNY laser. We performed a histopathological study on eight Korean women who had considerable improvement in their melasma lesions after a series of low‐fluence QSNY laser treatments. Compared with nonlesional skin, samples from melasma lesions showed increased reactivity in melanin (Fontana–Masson staining) and in melanogenesis‐associated proteins, including α‐melanocyte‐stimulating hormone, tyrosinase, tyrosinase‐related protein (TRP)‐1, TRP–2, nerve growth factor and stem cell factor. After laser treatment, the melasma skin showed a decrease in the number of melanosomes and reduced expression of melanogenesis‐associated proteins. Expression levels of the melanogenic proteins were reduced after laser treatment, although the number of melanocytes was unchanged even in hypopigmented areas. Based on these results, we believe that repeated application of low thermal energy via QSNY laser may result in damage to melanocytes and long‐lasting hypopigmentation.

Clinical and pathological characteristics of extradigital and digital glomus tumours: a retrospective comparative study.

Background  Most glomus tumours are located in the digits, especially in subungual areas. Less is known, however, about the clinical characteristics of extradigital glomus tumours.

Clinical and Histologic Features of 64 Cases of Steatocystoma Multiplex

Steatocystoma multiplex (SM) shares many clinical features and may show overlapping histopathological features with eruptive vellus hair cyst (EVHC). Clinical data and pathologic features of 64 patients with SM were evaluated in detail. Most of the cases were sporadic, with an average onset age of 26 years and distribution on the arms, chest, axillae, and neck. All cases exhibited eosinophilic cuticle and lack of granular layer, and 17–42% displayed vellus hair, hair follicles, keratin, and smooth muscle components within the cavity, in the wall, or adjacent to it. The results of this study add further evidence to the hypothesis that SM is a hamartomatous condition and that SM and EVHC are variants of one disorder which originates in the pilosebaceous duct.

Majocchi's granuloma of the vulva caused by Trichophyton mentagrophytes

We report a case of Majocchis granuloma caused by Trichophyton mentagrophytes on the vulva in a 23‐year‐old girl who had used topical steroids for many years. Her dog was a source of the infection.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica: comparison of lesional T-cell subsets and investigation of viral associations

Background: Pityriasis lichenoides (PL) exhibits a broad clinical spectrum that includes both acute and chronic forms. The precise biologic mechanisms underlying PL remain unclear.