Hemangioma is a vascular tumor of infancy that is well-known for its rapid growth during the first weeks to months of a child's life followed by a spontaneous but slow involution. During the proliferative phase, the vessels are disorganized and composed of immature endothelial cells but are not leaky (1) , perhaps due to the abundance of α-smooth muscle actin (α-SMA)-positive perivascular that circumscribe the vessels (Figure 1). When the tumor involutes, the vessels mature and enlarge but are reduced in number. Fat, fibroblasts and connective tissue replace the vascular tissue, with few large feeding and draining vessels evident. This article is protected by copyright. All rights reserved.

We read with interest two recent studies which established that High Definition Optical Coherent Tomography (HD-OCT), a newly released skin imaging technique, facilitates the in vivo diagnosis of non-melanoma skin cancers (1, 2). However, to the best of our knowledge there is no data available regarding HD-OCT and melanoma. A 61-year-old man, skin type II, with a previous history of melanoma 10 years before consulted for a follow-up visit. Clinical and dermoscopic examination pointed to two suspicious pigmented lesions in the right pectoral region and on the left scapula. RCM examination using a commercially available VivaScope (®) 1500 (Lucid-Tech Inc., Henrietta, NY, USA) disclosed the same RCM features for both lesions: architectural disarray and presence of pagetoid cells in the epidermis, non-edged papilla and atypical nests of melanocytes at the dermal-epidermal junction (Figure 1 a, b). A commercially available full-field HD-OCT system (Skintell; Agfa HealthCare, Mortsel, Belgium) This article is protected by copyright. All rights reserved.

BACKGROUND:

Although propranolol has become the first line therapy of infantile hemangiomas (IH), no study has yet investigated factors associated with the risk of relapse in children with IH treated with propranolol after treatment cessation.

OBJECTIVE:

To compare factors associated with the risk of relapse in children with IH treated with oral propranolol

PATIENTS AND METHODS:

We conducted a single-centre retrospective observational study. All files and photographs of patients with IH aged 5 months or less at the time of treatment initiation and who were seen between June 1(st) 2008 and December 31(th) 2011at the National Reference Center for rare skin diseases of Bordeaux were retrospectively reviewed.

RESULTS:

A total of 158 children were included of whom 118 had not relapsed (R-) and 40 had relapsed (R+).52 patients were boys and 106 were girls (sex ratio M/F, 1:2), and 19 had a segmental IH (12%). When conducting multivariate analysis, only IH with a subcutaneous component and those with segmental distribution were independently associated with relapse.

CONCLUSIONS:

Our study shows that segmental IH as well as hemangiomas with a deeper component are more at risk for relapse and should thus beneficiate of closer follow-up after treatment interruption and/or longer treatment. This article is protected by copyright. All rights reserved.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects 4% of children. The exact etiology of PG remains obscure. It has been reported to occur in association with a variety of systemic disease that includes a wide spectrum of immunologic disorders. To date, however, no cases of PG have been described in the context of common variable immunodeficiency (CVID). This article is protected by copyright. All rights reserved.

BACKGROUND:

Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin.

OBJECTIVE:

The aim of this study was to quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilising autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders.

METHODS:

Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathological examination. In situ visualisation of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions.

RESULTS:

Based on the MPM-detected elastin-specific autofluorescence in skin sections, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using the DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other elastin-related skin disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We also imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in patients in vivo.

CONCLUSIONS:

MPM has the potential for non-invasive in vivo visualisation of elastic fibres in the dermis with near histological resolution. The DEMI is a novel approach to enable objective assessment of elastic fibres to support diagnosis as well as monitoring of disease progress or therapy of elastin-related skin disorders. This article is protected by copyright. All rights reserved.

MADAM, Papillon-Lefèvre syndrome (PLS) [OMIM: 245000] is a rare autosomal recessive genodermatosis caused by mutations in CTSC(1) and characterized by palmoplantar keratoderma, psoriasiform lesions over the extensor surface of extremities and severe gingivitis followed by loss of teeth(2,3) . CTSC encodes cathepsin C (CTSC), a lysosomal cysteine protease required for the activation of granule-associated serine proteases in inflammatory cells(1) . Seventy-seven distinct CTSC mutations have been identified, most of which are missense mutations that alter protein folding and function (Human Gene Mutation Database (Institute of Medical Genetics, Cardiff University, UK)). Here, we show a novel homozygous nonsense mutation, p.Lys106X, which results in a deficiency of the mutant mRNA because of nonsense-mediated mRNA decay in a patient with PLS that has atypical clinical feature of retention of all the permanent teeth at over 40 years of age. This article is protected by copyright. All rights reserved.

BACKGROUND:

Melanoma is responsible for almost 80% of the deaths attributed to skin cancer. Stem cells, defined by CD133 expression, have been implicated in melanoma tumor growth, but their specific role is still uncertain.

OBJECTIVES:

We hypothesized that the phenotypic heterogeneity of human cutaneous melanomas is related to their content of CD133+ cells.

METHODS:

We compared the percentages of CD133+ cells in 29 tumors from four classic types of melanoma: lentigo maligna melanoma (LMM), superficial spreading melanoma, nodular melanoma, and acral lentiginous melanoma (ALM). Also, we compared the percentages of CD133+ cells in melanomas with different degrees of exposure to ultraviolet light: 16 melanomas from skin with chronic sun-induced damage and 13 melanomas from skin without such damage.

RESULTS:

We found a statistically significant increase of CD133+ cells in three different contexts: in melanomas arising on skin with signs of chronic sun-induced damage versus non-exposed skin, in melanomas "in situ" versus invasive melanomas, and in LMM versus ALM. The proportions of CD133+ cells did not differ among samples of normal skin with different degrees of sun exposure. A distinct subpopulation of CD133+CXCR4+ cancer stem cells (CSCs) was identified and shown to be related with the invasive phenotype of the tumors.

CONCLUSIONS:

Here, we provide evidences showing, for the first time, that an increase in the CD133+ cell content is associated both with melanomas arising on skin with signs of chronic sun-induced damage and in melanomas "in situ" with better prognostic. Moreover, our study further confirms the existence of a subpopulation of CD133+CXCR4+ CSCs in cutaneous melanomas with invasive phenotype and bad prognostic. This article is protected by copyright. All rights reserved.

BACKGROUND:

Cadherin switch in melanoma, with loss of E-cadherin and up-regulation of N-cadherin, is believed to underlie melanoma cell detachment from the epidermis and promotion of dermal and vascular melanoma invasion. The tumour suppressor PTEN has been suggested as a potential regulator of this cadherin switch.

OBJECTIVES:

To study the biological and clinical implications of cadherin switch and PTEN expression in melanoma progression.

METHODS:

We constructed tissue microarrays from primary tumour samples from 393 formalin-fixed paraffin-embedded melanomas diagnosed between 2001 and 2006. Median follow-up was ten years. Tissue microarray sections were stained by immunohistochemistry for E-cadherin, N-cadherin, and PTEN, and expression was analysed semi-quantitatively.

RESULTS:

Breslow thickness correlated strongly with reduced/absent PTEN expression (p<0.0001), low E-cadherin expression (p<0.0001), high N-cadherin expression (p<0.0001) and the combination of low E-cadherin and high N-cadherin expression (cadherin switch profile; p=0.001). There was a significant association between reduced/absent PTEN expression and the presence of the cadherin switch profile (p=0.03). In univariate analyses, a low E-cadherin expression significantly predicted an adverse overall-relapse-free (p=0.04), melanoma-specific (p=0.03), and distant-metastasis-free (p=0.01) survival; reduced/absent PTEN predicted an adverse overall-relapse-free survival (p=0.006), and the cadherin switch profile predicted an adverse melanoma-specific (p=0.005), and distant-metastasis-free (p=0.01) survival. In multivariate analysis, the cadherin switch profile was an independent prognostic marker of melanoma-specific (p=0.04) and distant-metastasis-free survival (p=0.02).

CONCLUSIONS:

Cadherin switch and reduced/absent PTEN expression are associated in melanoma, and both factors may play important roles in the progression of melanoma. This article is protected by copyright. All rights reserved.

INTRODUCTION:

Anti-tumour necrosis factor (anti-TNF-α) agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents.

MATERIALS AND METHODS:

Single nucleotide polymorphisms (SNPs) for TNF-α promoter and IL12B/IL23R genes, and presence of HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months (PASI and BSA).

RESULTS:

Patients with the TNF-α-238GG genotype more frequently achieved PASI75 at six months (82.5 vs. 58.8, p=0.049). At six months patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI and BSA (83.1 vs. 92.7, p=0.004; 82.7 vs. 92.6, p=0.009) and more frequently achieved PASI75 (71.4 vs. 96.3, p=0.006). More patients with the TNFα-1031TT genotype achieved PASI75 at three months (90.8 vs. 75.7, p=0.047) and six months (85.5 vs. 65.7, p=0.038) and demonstrated superior improvements in PASI at six months (89.9 vs. 78.7, p=0.041). Patients with the IL23R GG genotype (rs11209026) achieved PASI90 at six months (66.3 vs. 0, p=0.006) more frequently and the improvement of PASI was also greater (86.8 vs. 67.8, p=0.013). Patients with HLA-Cw6 haplotype showed poorer response than those without this haplotype.

CONCLUSION:

This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient. This article is protected by copyright. All rights reserved.

BACKGROUND:

Propranolol is now widely used to treat severe infantile hemangiomas. Very few cases of propranolol-resistant infantile hemangiomas (PRIHs) are mentioned in the literature.

OBJECTIVES:

To describe the characteristics of PRIHs.

METHODS:

A NATIONAL, MULTICENTER, RETROSPECTIVE, OBSERVATIONAL STUDY WAS CONDUCTED FROM: February 2011 to December 2011. All PRIH patients evaluated by the members of the "Groupe de Recherche Clinique en Dermatologie Pédiatrique" from 1 January 2007 to 1 December 2011 were eligible.

RESULTS:

Among 1130 patients treated with propranolol for infantile hemangioma, 10 (0.9%) had PRIHs. Hemangioma propranolol-resistance was observed at all ages during early childhood and at any proliferation stage.

CONCLUSION:

PRIH is a rare phenomenon that raises questions and merits further investigation. This article is protected by copyright. All rights reserved.