Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B.

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment.

Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas.

Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.

Long-term recurrence rate of large and difficult to treat cutaneous squamous cell carcinomas after superficial radiotherapy.

BACKGROUND: Surgical excision is the gold standard for cutaneous squamous cell carcinoma (cSCC), however its application is limited in specific cases. Superficial radiotherapy (RTx) is an alternative treatment option, but long-term follow-up data are limited. OBJECTIVE: To determine the outcome of superficial RTx of cSCC in correlation to histological differentiation grade and tumor localization. METHODS: The outcome of 180 large cSCCs after superficial RTx between 1960 and 2004 was retrospectively reviewed. RESULTS: Mean tumor size was 3.5 cm(2) (SD 7.5) and mean follow-up period was 4.9 years (SD 4.7). Relapse-free survival was 95.8 and 80.4% after 1 and 10 years. Two-year relapse-free survival was 94.8% for good, 88.9% for moderate and 85.7% for poor differentiated tumors. Five-year relapse-free survival was highest in cSCCs located around the eyes (100%) and cheeks (90.9%). CONCLUSION: Superficial RTx is an effective alternative for cSCC if surgery is difficult due to localization or concomitant disease.

[Epidemiology of epithelial skin cancers]. / Epidémiologie des cancers épithéliaux de la peau.

With no less than 15,000 estimated new cases diagnosed per year, non melanomatous carcinomas are the commonest cutaneous cancers in the Swiss population. About 1 in 3 new cancer case is a basal (BCC) or a squamous cell carcinoma (SCC). Incidence rates are steadily increasing, faster for BCC than SCC. Rates are higher for men than women and increase exponentially with age. Systematic population-based registration of non melanomatous skin cancers faces many challenges that few cancer registries can meet. Rates of these cancers in Switzerland are among the highest in Europe. Primary and secondary nationwide prevention campaigns have been carried out for nearly 20 years with a focus on the deadliest cutaneous cancer: melanoma. However, detection of non melanomatous skin cancers benefits from these campaigns since prevention messages and means of early detection are similar for melanomas and other skin cancers.

Orodigital pemphigus vulgaris: a pathogenic role of anti-desmoglein-3 autoantibodies in pemphigus paronychia?

Paronychia is a rare complication of pemphigus vulgaris (PV), and the immunological profile of patients with digital disease has not been assessed so far. We report 2 cases of PV with oral mucosa and periungual involvement, who had high titers of anti- desmoglein (Dsg)-3 circulating antibodies. These observations raise the possibility that expression of Dsg-1 and Dsg-3 in distinct areas of periungual skin is disease specific and that anti-Dsg-3 antibodies alone may have an as yet unrecognized importance for the development of paronychia in PV.

Cannabis arteritis.

Cannabis arteritis is a serious peripheral vascular disease affecting young adults consuming cannabis. An increasing number of cases have been recently reported in Europe. The risk of amputation is high. Cannabis arteritis is often confused with atherosclerosis. We present a new case in which complete arterial revascularization was obtained with early aspirin treatment. Cannabis arteritis should be therefore distinguished from peripheral arterial disease caused by atherosclerosis, which is typically not reversible. Early diagnosis and treatment are essential to avoid an irreversible vascular occlusion and amputation.

Mycosis fungoides in a lung transplant recipient with advanced ciclosporin nephropathy: management with mechlorethamine and subsequent renal transplantation.

Posttransplant cutaneous T cell lymphomas are rare and have been reported to have a poor prognosis. We report the case of a follicular mycosis fungoides in a lung transplant recipient who was successfully treated with topical mechlorethamine, prior to subsequent renal transplantation.

First case of bacteremia and multifocal cellulitis due to Helicobacter canis in an immunocompetent patient.

Bacteremia due to Helicobacter canis has been reported in a patient with X-linked hypogammaglobulinemia. Here we report on the first human case of H. canis bacteremia in an immunocompetent host. Identification of the organism was made by genetic and phylogenetic analyses of the complete 16S rRNA sequence.

Fast and reliable PCR/sequencing/RFLP assay for identification of fungi in onychomycoses.

Fusarium spp. and other non-dermatophyte fungi are repeatedly isolated from abnormal nails. To investigate whether these fungi are the aetiological agents of infection or simply transient contaminants, a PCR/sequencing/RFLP assay was developed for direct and routine identification of the infecting fungi in onychomycosis. Fungal DNA was readily extracted using a commercial kit after dissolving nail fragments in a Na2S solution. Amplification of part of the 28S rDNA by PCR was performed with universal primers and the fungal species were identified by sequencing. The PCR/sequencing results were comparable with microbiological identification from the same nail sample. In addition to dermatophytes, Fusarium spp. and other less frequently isolated non-dermatophyte fungi were identified as single fungal agents in onychomycosis. Moreover, mixed infections were clearly demonstrated in 10% of cases by RFLP analysis of PCR products. Identification of infectious agents could be obtained in 2 days, whilst results from fungal cultures take 1-3 weeks. Rapid and reliable molecular identification of the infectious fungus expedites the choice of appropriate antifungal therapy, thereby improving the cure rate of onychomycosis.

A kerion celsi caused by Microsporum gypseum: unusual direct mycological examination.

A case of kerion celsi caused by Microsporum gypseum is documented. The patient was a 6-year-old girl with a 2-cm purulent lesion on the scalp. Direct mycological examination of the hair showed hyphae with extremely numerous spindle-shaped macrospores. The species identification was confirmed by 28S ribosomal DNA sequencing. The presence of numerous macrospores is unusual in direct mycological examination, but could be an indication for M. gypseum.

Irradiation therapy: from UV light to electron beam.

Irradiation therapy represents one of the mainstay treatment modalities in cutaneous T-cell lymphomas. For the patch and plaque stages UV therapy is mostly used. Among UV light treatment broadband UVB is less effective than narrow band UVB. If these modalities are not sufficient, then PUVA therapy is indicated and might be used in even more advanced stages, including the erythrodermic stage of the disease. For resistant cases and remaining tumors, conventional radiotherapy or electron beam therapy is the treatment of a choice. If the disease is widespread, total skin electron beam radiation gives excellent results. One should not forget the possibility of combining UV therapy with radiotherapy or electron beam radiation, or with chemo- and immunotherapy respectively.