Marie-Annick Reginster

Dermal Ultrastructure in Low Beighton Score Members of 17 Families with Hypermobile-Type Ehlers-Danlos Syndrome

The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH.

Smouldering malignant melanoma and metastatic dormancy: an update and review.

The fund of knowledge regarding the versatility of presentation of MM metastases is still quite incomplete. The recent literature pertaining to the current understanding of the mechanisms underlying two special features of MM metastasis is reviewed. On the one hand, a long disease-free interval (MM dormancy) may occur before the surge of overt metastases. On the other hand, the so-called MM smouldering phenomenon refers to the condition where regional metastases wax and wane for long periods of time on restricted skin regions. It is important to emphasize that local micrometastases often predict sentinel lymph node involvement but may not reflect progression of the primary MM to full-blown visceral metastatic competence. It is likely that a combination of factors impacts the versatile MM metastasic progression. Among the main factors, one has to mention the phenotypic heterogeneity and variability in the phenotype of MM cells, the presence of MM stem cells and MM cells engaged in an amplification proliferation pool, as well as the host immune response, and possibly the induction of a particular stromal structure and vascularity.

Molecular Dermatopathology in Malignant Melanoma

At present, immunohistochemistry is taken for granted in the establishment of malignant melanoma (MM) diagnosis. In recent years, molecular diagnosis in dermatopathology has benefited from a vast array of advances in the fields of genomics and proteomics. Sensitive techniques are available for detecting specific DNA and RNA sequences by molecular hybridization. This paper intends to update methods of molecular cytogenetics available as diagnostic adjuncts in the field of MM. Cytogenetics has highlighted the pathogenesis of atypical melanocytic neoplasms with emphasis on the activation of the mitogen-activated protein kinase (MAPK) signalling pathway during the initiation step of the neoplasms. 20 to 40% of MM families have mutations in the tumour suppressor gene p16 or CDKN2A. In addition, somatic mutations in p16, p53, BRAF, and cKIT are present in MM. Genome-wide scan analyses on MM indicate positive associations for genes involved in melanocytic naevi, but MM is likely caused by a variety of common low-penetrance genes. Molecular dermatopathology is expanding, and its use in the assessment of melanocytic neoplasms appears to be promising in the fields of research and diagnosis. Molecular dermatopathology will probably make its way to an increased number of diagnostic laboratories. The expected benefit should improve the patient management. This evolution points to a need for evolution in the training requirements and role of dermatopathologists.

Intense Pulsed-Light Therapy for Proliferative Haemangiomas of Infancy

Infantile haemangioma therapy has long been a wait-and-see policy. Since recent development of laser and light therapy, pulsed dye laser has been successfully used for treating superficial haemangiomas. Few studies have been published about treatment with intense pulsed light (IPL) to assess the risk/benefit of IPL in the treatment of infantile haemangiomas during their early proliferative phase. In the present retrospective cohort study, we retrieved data about a series of 14 Caucasian children (median age: 4.8 months) with infantile haemangiomas treated with Photoderm Vasculight flash lamp. All patients experienced a rapid regression of the haemangiomas after 3 treatments on average. Few adverse events were noted, including ulceration and crusts. No residual scarring and cosmetic damages were noticed. Fast growing haemangiomas should be treated with light therapy as soon as possible. This technology is safe, efficient, inducing regression, and preventing any further functional and aesthetic complications. The benefit-risk ratio favours the treatment of most types of haemangiomas which are out of the scope of betablocker administration.

Giant morphea-form basal cell carcinoma of the umbilicus: Successful debulking with vismodegib

Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus. A sequential treatment was initiated with debulking using vismodegib 150 mg per day for 4 months, followed by reconstructive surgery. To the best of our knowledge, this is the first report of a giant basal cell carcinoma of the morphea-form type of the umbilicus. The sequential treatment plan reduces the duration of vismodegib inherent adverse effects and significantly reduces the tumor mass prior to surgery. Besides increasing adherence to vismodegib treatment, this approach facilitates the surgical technique and improves cosmetic outcome.

Melanoma masquerading as nonmelanocytic lesions.

Increased awareness among dermatologists as well as the development of dermoscopy and sequential dermoscopy have contributed significantly toward an increase in the diagnostic accuracy of pigmented melanoma and even of amelanotic melanoma. However, the dermatologist’s nightmare is the small group of melanomas that present as common skin diseases, often associated with a significant delay in diagnosis and hence a poor prognosis. The study was carried out to prospectively assess the number of melanomas lacking any clinical suspicion of melanoma and to describe their clinical and histological features over a 6-year observation period in an University Tertiary Skin Cancer Center. Out of 502 cases of newly diagnosed cases of melanoma, seven (1.4%) nonpigmented and nonamelanotic cases of melanoma were identified. The mean age of the patients was 69 years (two females/five males). All cases were discovered by chance on a punch biopsy. The clinical diagnostic suspicions were basal cell carcinoma, fungal intertrigo, keratoacanthoma, lichenoid keratoma, diabetic foot ulcer, eczema, and necrotic pressure ulcer. Dermoscopy, performed after the punch biopsies, was only partially contributive. The mean histological thickness was 2.7 mm, the mean number of mitoses was 7/mm2, local micrometastases were present in 5/7 (71%), the mean Ki67 count was 18.9%, and a positive sentinel lymph node was observed in 4/6 (66%) cases. Nonpigmented and nonamelanotic melanomas are rare, are at high risk, and have a poor prognosis because of a delayed diagnosis. Dermoscopy is only of partial diagnostic aid. Treatment resistance or atypical behavior of the above-mentioned lesions should lead to biopsy.

Corneosurfametry and Corneoxenometry

Corneosurfametry and corneoxenometry are two related investigative methods allowing safe assessment of some irritation potential of surfactants and other xenobiotics, respectively. The method entails harvesting a sheet of the stratum corneum using the cyanoacrylate skin surface procedure. The neat or diluted test product is applied ex vivo for a given period of time at defined temperatures. The material is then rinsed and stained, and the color is measured using reflectance colorimetry in the L*a*b* system. The more the color is intense, the more the product is at risk of in vivo irritation.