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Zusammenfassung. Vaskulitiden sind eine heterogene Gruppe von Erkrankungen, die unterschiedlich klassifiziert werden, zum Beispiel nach der Grösse des betroffenen Gefässes oder nach primärer und sekundärer Ätiologie. Die Haut ist am häufigsten betroffen ist, sie kann sowohl isoliert als auch im Rahmen von systemischen Formen involviert sein. Die Kombination der Hautläsionen, deren anatomischer Lokalisation und Informationen zum Zeitablauf geben Hinweise für die Differenzialdiagnose. Purpura, Blasen, Nekrosen, Ulzerationen und allenfalls eine Livedo sind charakteristische Manifestationen. Konstitutionelle Symptome wie Gewichtsverlust, Abgeschlagenheit, Fieber und Arthralgien sind hinweisend auf eine systemische Form. Wichtig ist die differenzialdiagnostische Abgrenzung von Vaskulopathien, die sich ähnlich manifestieren können. Am häufigsten beim Erwachsenen ist die kutane leukozytoklastische Angiitis, beim Kind die IgA-Vaskulitis (Purpura Schönlein-Henoch). Bei diesen kommen diverse Auslöser in Frage: Infektionen, Medikamente, Autoimmunerkrankungen und Malignome, wobei bis zu 50% ätiologisch ungeklärt bleiben. Hautbiopsien und Laborparameter, allenfalls ergänzt durch Bildgebung, sind wichtige Schritte im Abklärungsprozedere. Die Behandlung richtet sich primär auf die Elimination einer möglichen Ursache. Die idiopathische kutane Form bildet sich meistens spontan zurück, die Behandlung ist symptomatisch. Bei schwererem Verlauf werden primär topisch Kortikosteroide oder Calcineurinantagonisten angewandt. Bei Therapieresistenz werden systemische Immunsuppressiva eingesetzt.

Cutaneous Vasculitides - Clinical Manifestations, Diagnosis, and Aetiology

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) can both present with histological dysplasia. Despite the presence of WHO-defined criteria for the evaluation of epithelial dysplasia, its assessment is frequently subjective (inter-observer variability). The lack of reproducibility in the evaluation of dysplasia is even more complex in the presence of a lichenoid inflammation. We evaluated dysplasia in 112 oral biopsies with lichenoid inflammation in order to study the inter-observer and the intra-observer variability.

Calciphylaxis and the arteriolosclerotic ulcer of Martorell (ASUM) represent two entities of cutaneous calcific arteriolopathies. Their differential diagnosis can be challenging, given similarities in their clinical and histological presentation. Calcification patterns have been proposed as a possible discriminative histological criterion, however, a systematic microstructural comparative analysis is lacking.The study aimed at a systematic comparative microstructural analysis of the calcification patterns in calciphylaxis versus ASUM.Skin biopsies of patients with leg ulcers due to calciphylaxis (20) and ASUM (69) diagnosed at three European wound care centres (Vienna, Bern, Zurich) were included. The extent of calcification, arteriolar calcification pattern and presence of extra-arteriolar calcification were assessed.All calciphylaxis and most ASUM patients (77%) presented with arteriolar calcification. Although the mean number of calcified vessels and the proportion of calcified area were significantly higher in calciphylaxis specimens (p = 0.003 and p = 0.0171), there was no significant difference in the pattern of arteriolar calcification (p = 0.177). Interestingly, extra-arteriolar calcification was detected in the majority of both calciphylaxis (93.3%) and ASUM samples (85.2%, p = 0.639). Notably, Alizarin Red S staining was superior to HE for the detection of calcifications of both entities (p = 0.014 and p 0.0001), and to von Kossa staining for ASUM samples (p = 0.0001). However, no differences could be observed between cases with uraemic and non-uraemic calciphylaxis or ulcerations located on the upper and lower leg.Our results indicate that extra-arteriolar calcification is not only present in calciphylaxis, but can also be detected in ASUM suggesting a lack of specificity for this finding. However, more specific calcification stains, such as Alizarin Red S, should be used in suspected cases, as calcifications may be overlooked using conventional HE staining.

BACKGROUND Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids. OBJECTIVE To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS. STUDY DESIGN Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12��weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters. RESULTS Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate. At 12��weeks, the mean clinical LS scores improved from 4.6 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p��=��0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, p��=��0.095). LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol 0.35; 95% CI 0.06 to 2.06, p��=��0.234). No drug-related serious adverse event occurred during the trial. CONCLUSIONS Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12��weeks treatment.

Background Moulages can greatly extend the possibilities of simulation in teaching and assessment. Since moulages that fit an educator’s exact needs are often unavailable commercially, this paper explains how 2-dimensional transfer tattoos can be independently developed, produced, and evaluated. Methods From representative photographs of the specific skin condition an analogue copy of the pathological finding is drawn. Once validated by the medical expert, it can be digitized by scanning and processed using graphics software. The final digital image file is printed onto transfer paper. Once applied and fixed onto the intended wearer, usually a simulated patient, its authenticity can be confirmed, and further transfer tattoos can be produced. Results Using this moulage technique we produced 10 different 2-dimensional transfer tattoos to date, including hematoma, Janeway lesions and splinter nails. These moulages are used in clinical skills training, formative and high-stakes summative assessment in undergraduate medical and nursing programs. Conclusions By sharing our development process for 2-dimensional transfer tattoos, health profession educators can produce their own that best fit their local educational needs. Due to their high authenticity and standardization, 2-dimensional transfer tattoos are ideal for use in high-stakes assessment.

International audience

Background: Multiple studies have compared the performance of artificial intelligence (AI)–based models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice. Objective: The objective of the study was to systematically analyse the current state of research on reader studies involving melanoma and to assess their potential clinical relevance by evaluating three main aspects: test set characteristics (holdout/out-of-distribution data set, composition), test setting (experimental/clinical, inclusion of metadata) and representativeness of participating clinicians. Methods: PubMed, Medline and ScienceDirect were screened for peer-reviewed studies published between 2017 and 2021 and dealing with AI-based skin cancer classification involving melanoma. The search terms skin cancer classification, deep learning, convolutional neural network (CNN), melanoma (detection), digital biomarkers, histopathology and whole slide imaging were combined. Based on the search results, only studies that considered direct comparison of AI results with clinicians and had a diagnostic classification as their main objective were included. Results: A total of 19 reader studies fulfilled the inclusion criteria. Of these, 11 CNN-based approaches addressed the classification of dermoscopic images; 6 concentrated on the classification of clinical images, whereas 2 dermatopathological studies utilised digitised histopathological whole slide images. Conclusions: All 19 included studies demonstrated superior or at least equivalent performance of CNN-based classifiers compared with clinicians. However, almost all studies were conducted in highly artificial settings based exclusively on single images of the suspicious lesions. Moreover, test sets mainly consisted of holdout images and did not represent the full range of patient populations and melanoma subtypes encountered in clinical practice. info:eu-repo/semantics/publishedVersion

Onychopapilloma is a fairly common lesion that is clinically typical enough to make the diagnosis. It is unique in that it stretches from the distal matrix all along the nailbed to the hyponychium. A case is described that developed pain eventually resulting in total excision. Histopathology revealed a malignant onychopapilloma. The differential diagnosis of this lesion is discussed.

Background: Prurigo pigmentosa (PP) is an inflammatory dermatosis typically reported in young Asian women and characterized by recurrent papulovesicular lesions resolving with a postinflammatory reticulated hyperpigmentation. Methods: We have included all consecutive patients with PP diagnosed in our tertiary center between 2013 and 2020. The clinical information was retrospectively collected from medical records. Results: We identified 14 patients with PP. The median age at the time of diagnosis was 29.5 years (range 17–43 years), while the female-to-male ratio was 13:1. Diagnostic delay varied from 10 days to 10 years (mean of 25 months). Light microscopy studies consistently showed presence of a lymphohistiocytic infiltrate in combination in 40% of cases with neutrophils. Interface changes were found in 60% of cases. In 6 (43%) of 14 cases, there was a chronological relationship between the starting of a new diet and the development of the first flares. Treatment with doxycycline in 9 patients resulted in a complete regression of the lesions. Limitation: This was a retrospective study in a tertiary referral hospital. Conclusions: Our observations indicate that PP is not so rare in Europe as previously thought and is often diagnosed after a long delay. Demographics, clinical characteristics and triggering factors in Caucasian patients are similar to those described in the Asian population. Diagnosis is based on the peculiar recurrent course and distinctive clinicopathological features. Tetracyclines represent the first-line therapy in PP.

International audience

Background: There are no proper management guidelines for nail apparatus melanoma (NAM). Objective: This study aimed to describe the clinical features, the presence of locoregional and distant metastases and disease-free and overall survival of NAM treated at our institution. Methods: A retrospective cohort review of patients with single, primary localized histopathologically confirmed NAM was performed. Collected data consisted of patients’ characteristics and tumor features. In addition, local recurrence, locoregional metastases, distant metastases, disease-free survival (DFS) and overall survival (OS) were used as the main outcomes in our analysis. Results: Thirty patients with NAM were included. The overall survival (OS) in our patients at 5 and 10 years was 85.6 and 73.4%, respectively. DFS was significantly higher in patients with primary tumor location in the hand and without tumor-infiltrating lymphocytes (p value = 0.01 and 0.04, respectively). The patients with in situ melanoma or Breslow thickness Conclusion: Primary tumor location in the hand and lower tumor thickness might be correlated with better patients’ survival. The study results suggest that total amputation might not be necessary in all NAM cases.

Journal of the American Academy of Dermatology : JAAD 86(3), 640-642 (2022). doi:10.1016/j.jaad.2021.02.009, Published by Elsevier, Amsterdam [u.a.]

International audience; Skin involvement in Waldenström's macroglobulinaemia is poorly described, and diagnosis of this disorder may be difficult. Many differential diagnoses are possible (other lymphomas, primary cutaneous lymphoma, etc.). Describing 2 aspects of Waldenström's macroglobulinaemia (infiltration by lymphoplasmacytic tumour cells or histological transformation into diffuse large B-cell lymphoma) allows the identification of clinical, histological and immunohistochemical diagnostic aids. Detection of the MYD88 L265P mutation is of interest. This study identified a characteristic clinical picture in non-transformed cases, and was able to distinguish between transformed and non-transformed cases by their severity and poor prognosis. Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the followup of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).

Background Angiogenesis is a key event in tumour growth. An infection with human papillomavirus (HPV) typically leads to benign tumours, such as warts (papillomas) on the skin and mucous membranes. The role of angiogenesis in skin warts is yet to be established. The present work evaluates the hypothesis that the development of skin warts is associated with alterations in the dermal vascularisation (dermal microvessel density/mm 2 , MVD). Methods Seventeen cases of cutaneous warts and eight cases of normal skin were studied. Dermal vessels were immunostained for CD31, CD34 and CD105. The ten areas with the highest number of microvessels were counted. Results The number of CD31 + , CD34 + and CD105 + vessels was significantly higher in cutaneous warts compared to that in normal skin (mean±SD: 45.71±22.63 vs 21.27±5.83, P=0.0062; 59.75±24.93 vs 17.13±5.67, P

In the oral mucosa, a precise classification of inflammatory lesions with a histopathological lichenoid inflammation represents a diagnostic challenge. Oral lichen planus (OLP) and oral lichenoid lesions (OLL) share several clinical and histopathological characteristics, therefore it is often difficult to distinguish between them. However, considering that the pathophysiologic mechanisms and the treatment approach of OLP and OLL are different, an early distinction of between these two diseases is meaningful.

is missing (Short communication)

Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive antitumor activity. However, it causes adverse effects, including lichenoid reactions. Cases of ICI-triggered bullous pemphigoid (BP) and anecdotally mucous membrane pemphigoid (MMP) have also been reported. We describe two new cases of pembrolizumab-triggered MMP, one of which was associated with cutaneous lichenoid lesions.

Introduction Le mycosis fongoide (MF) de l’enfant est rare. Son profil evolutif a l’âge adulte est mal connu. Notre objectif etait de decrire les profils epidemiologique/clinique/histologique/therapeutique et evolutif du MF de l’enfant. Materiel et methodes Dans cette etude multicentrique retrospective, nous avons inclus les patients avec MF confirme avant l’âge de 18 ans ; traitements et evolution (si suivi superieur a 1 an) ont ete analyses. Resultats 47 patients ont ete inclus, dont 40 analysables pour le suivi (âge median aux premiers symptomes 7,8 ans, au diagnostic 11 ans, sexe ratio M/F = 3/1). Au diagnostic, 85 % etaient au stade I. Les lesions etaient en patchs dans 64 %, hypopigmentees dans 41 %. La forme histologique etait pilotrope dans 20 cas (43 %), dont 12 avec mucinose folliculaire. Le phenotype etait CD8+ dans 19 % des cas, sans association significative avec la presence de lesions hypopigmentees (p = 0,136). Une abstention therapeutique initiale etait proposee a 6/40 (15 %) des patients, 28/40 (70 %) etaient traites par traitements locaux (topique/phototherapie) et 6/40 (15 %) recevaient un traitement systemique. Une reponse clinique etait obtenue chez 28/40 (70 %) patients (complete RC 10 et partielle RP 18). Une RC etait plus souvent observee en 1ere ligne dans les formes CD8 + (p = 0,049). Une rechute etait constatee chez 14/40 (35 %) patients (delai median pour la 1ere rechute : 22 mois). Apres une duree mediane de suivi de 57 mois (12–216), une reponse clinique etait observee dans 31/40 (78 %) des cas (RC 14, RP 17), une stabilite dans 6 (15 %), une progression dans 3 (7,5 %) (1 stade IIB apres 10 ans et 2 stades IV apres 1 et 5,6 ans) et une transformation chez 4 patients (10 %) dont les 3 ayant progresse et 3 apres plus de 12 ans (phenotype CD4+ pour 3/4). Chez les 16 patients devenus adultes, 14 (88 %) ont evolue vers un MF de l’adulte : âge median aux premiers symptomes et au diagnostic plus tardif (10,8 et 12,5 ans), phenotype majoritairement CD4+ (12/14, 86 %). A la derniere visite, 9/14 (64 %) etaient toujours en reponse clinique (RC 2, RP 7). Discussion Une predominance masculine est observee dans cette serie de MF pediatrique. La forme hypopigmentee est plus frequente que chez l’adulte, mais non associee a la reponse clinique. Le phenotype CD8+, trouve dans 19 % des cas (taux relativement bas par rapport aux autres series pediatriques) n’est pas particulierement associe aux formes hypopigmentees mais correle a une meilleure RC en 1ere ligne. Les traitements locaux semblent efficaces dans la plupart des cas. L’evolution est majoritairement indolente avec un bon pronostic d’ensemble. Cependant une transformation souvent tardive est constatee chez presque 10 % des patients, taux superieur a celui des autres series pediatriques mais similaire a celui observe chez l’adulte (10 a 22 %). La persistance de la maladie a l’âge adulte est frequente et incite a une surveillance au long cours.

Clinical differential diagnosis of arteriolosclerotic ulcers of Martorell is challenging due to the lack of clearly affirmative instrument-based diagnostic criteria. The aim of this study was to develop vascular histomorphological diagnostic criteria differentiating Martorell ulcers from other types of leg ulcers. The histomorphology of patients diagnosed with arteriolosclerotic ulcers of Martorell (n���=���67) was compared with that of patients with venous leg ulcers, necrotizing leukocytoclastic vasculitis, pyoderma gangrenosum, and non-ulcerative controls (n���=���15 each). In a multivariable logistic regression model, the rates of arteriolar calcification (odds ratio (OR) 42.71, 95% confidence interval (CI) 7.43-443.96, p���

Introduction Le mycosis fongoide (MF) est le plus frequent des lymphomes T cutanes (LTC). L’evolution est habituellement indolente avec une survie a 5 ans de 88 %. Les formes histologiquement pustuleuses de MF (MFP) sont rares mais semblent, dans des cas isoles, avoir un pronostic defavorable. Materiel et methodes Cette etude prospective a regroupe tous les MF histologiquement pustuleux (pustules folliculaires ou epidermiques) diagnostiques dans un centre expert depuis le 01/01/2009, et une revue de la litterature. Les donnees cliniques, histologiques, immunophenotypiques et de clonalite ont ete recueillies par fiche standardisee. Les donnees evolutives ont ete comparees a la cohorte des MF du PHRC KIRs (cohorte KIRs, n = 78) du GFELC, realisee de 2009 a 2011. Resultats Vingt deux patients ont ete inclus (6 % des MF diagnostiques dans le centre expert sur la periode), et associes aux 14 cas de la litterature. 78 % (28/36) etaient des hommes, avec un âge median au diagnostic de 62,5 ans (30-88 ans). 61 % (20/31) avaient necessite plus d’une biopsie pour arriver au diagnostic de MFP (delai median avant diagnostic de 14,5 mois), avec un diagnostic de maladie inflammatoire dans 24 % des cas (8/34, dont 3 folliculites suppurees, 2 dermatoses psoriasiformes, 2 dermatoses pustuleuses). Cliniquement, 91 % des patients (31/34) avaient des plaques, 52 % des pustules (18/34, figA) et 24 % une desquamation psoriasiforme (8/34). 78,6 % des patients evaluables (22/28) ont presente une evolution agressive (tumeurs, adenopathies, atteinte viscerale), vs 9 % (8/78) dans la cohorte KIRs (p Discussion Le MFP semble etre une variante particulierement agressive de MF, dont le diagnostic histologique est rendu difficile par la presence de pustules, confondues avec une dermatose inflammatoire. L’infiltration neutrophilique pourrait temoigner de caracteristiques des cellules tumorales de MF plus agressifs (production cytokinique particuliere). Inversement, un terrain inflammatoire ou une infection cutanee superficielle pourraient constituer un microenvironnement favorable aux cellules tumorales.

BACKGROUND Direct immunofluorescence microscopy (DIF) studies constitute the gold standard for diagnosis of bullous pemphigoid (BP) but depend on the availability of specialized laboratories and often on an additional skin biopsy specimen. OBJECTIVES To assess the value of immunohistochemical analyses (IHCA) in the diagnosis of BP using formalin-fixed, paraffin-embedded skin biopsy specimens as an alternative to DIF; and to study the correlation between the results of IHCA and the presence of histological subepidermal blister formation and of circulating autoantibodies by indirect immunofluorescence studies using split skin or by enzyme-linked immunosorbent assays. METHODS We included all patients newly diagnosed with BP evaluated between 2008 and 2010. There were 51 consecutive skin biopsy specimens obtained from 38 patients with BP with positive DIF. RESULTS By IHCA, deposits of immunoreactants were found in 45% of all tested cases. Deposits of C3d, IgG, IgM, IgE and IgA were found in 37%, 23%, 2%, 0% and 0% of cases, respectively. Deposits of C3d and/or IgG were found in 79% of the 24 cases with a blister and in 83% of the 12 cases with subepidermal blistering and positive immunoserological analyses, respectively. CONCLUSIONS In contrast to previous studies, our findings in an unselected patient cohort indicate that IHCA are not sufficiently sensitive to replace DIF studies for confirming the diagnosis of BP. IHCA sensitivity significantly increases in the presence of histological blistering and/or of circulating autoantibodies. IHCA represents a potential rescue diagnostic technique only if specialized laboratories and/or a second biopsy specimen for DIF are unavailable.

BACKGROUND Bowen disease is the most frequent nail malignancy, usually seen as a verrucous plaque of the nail in men. OBJECTIVE To characterize the affected patient population, the clinical manifestations, the diagnostic delay and diagnostic steps, and presence of human papilloma virus (HPV) infection. METHODS We retrospectively evaluated all cases of Bowen disease of the nail unit over a period of 9 years. Data were obtained from our electronic database. Human papilloma virus genotype was assessed in biopsy specimens by polymerase chain reaction (PCR) sequencing. RESULTS We identified 12 cases of Bowen disease of the nail unit in 10 patients. Mean age at onset was 52 years, with a male predominance of 90%. The thumb and middle finger were the most frequently affected (66%). Fifty percent of the lesions presented as periungual and subungual verrucous tumours. Patients sought medical evaluation after a mean delay of 5.7 years; histopathological diagnosis was made after a mean delay of 3.2 years. HPV infection was identified in 75% of the cases. CONCLUSIONS Any recently appeared verrucous lesion of the nail unit in men above the age of 40 years should raise the suspicion of Bowen disease and lead to further histopathological diagnostic procedures.

BACKGROUND Histopathology is often essential to establish an accurate diagnosis. Pathology laboratories are scarce in most Sub-Saharan Africa where dermatopathology is a developing field. In resource-poor countries, most specimens are analyzed only after hematoxylin and eosin staining. The availability of special stains is very limited and restricted to only few centers. The aim of this study is to analyze the extent of dermatopathological cases which can be adequately diagnosed after hematoxylin and eosin alone. Secondly, to investigate which cases required further special stains. METHODS All skin specimens submitted to two University Hospitals (Tanzania and Kenya) were included in this study. All specimens were first analyzed with hematoxylin and eosin and a diagnosis established when possible. All cases in which an accurate diagnosis after hematoxylin and eosin only was not possible, were registered and evaluated after further special stains. RESULTS A total of 386 specimens were examined. A proper histopathologic diagnosis with hematoxylin and eosin alone was possible in 344 (89.1%) samples. In 45 (11.6%) cases, mostly skin infections, further special stains were necessary. CONCLUSION A proper histopathologic diagnosis was possible after hematoxylin and eosin alone in almost 90% of the specimens submitted to the two laboratories in Sub-Saharan Africa.

The histopathological differentiation of melanocytic nevi from malignant melanoma (MM) is based on well-known criteria, and is straightforward in the vast majority of cases. However, there are few cases of melanocytic lesions (ML), the diagnosis of which is very challenging or even impossible. Here we have studied several morphological characteristics with particular focus on elastic fibers (EF) to identify features, helpful for the distinction between nevi and MM. In a monocentric retrospective study we have analyzed 14 morphological histological characteristics in 30 MMs and 90 nevi, encompassing 30 compound/dermal nevi, 30 junctional nevi, 30 dysplastic nevi. All consecutive cases were retrieved from the archives of our tertiary referral centre during the 6-month study period. Nine characteristics including loss of EF in the ML, loss of EF in lesional fibrosis, pushing of the EF, UV-elastosis, loss of rete ridges of the epidermis, regression of the ML, atrophy of the epidermis, pigment incontinence, and concentric eosinophilic fibroplasia (CEF) showed a statistical significant difference (p 2) distinguishing nevi from MM. Loss of EF was found in 73.1% of MM cases, but in less than 2.5% of nevi. We identified nine morphological characteristics that are helpful to differentiate melanocytic nevi from MM. A loss of the EF in a ML appeared to be highly associated with MM.

Despite advances in understanding the underlying mechanisms of flap necrosis and improvement in surgical techniques, skin flap necrosis after reconstructive surgery remains a crucial issue. We investigated the efficacy of electroporation-mediated IL-10 gene transfer to random skin flap with an aim to accelerate wound healing and improve skin flap survival. Nine male Wistar rats (300-330 g) were divided in two groups (a) control group (n = 5), only surgery no gene transfer, and (b) experimental group, received electroporation-mediated IL-10 gene transfer 24 h before the surgery as prophylaxis (n = 4). Random skin flap (McFarlane) was performed in both groups. Planimetry, Laser Doppler imaging, and immunohistochemistry were used to evaluate the effect of IL-10 gene transfer between study groups at day 7. Electroporation-mediated IL-10 gene transfer decreased percentage of flap necrosis (p value = 0.0159) and increased cutaneous perfusion compared to the control group (p value = 0.0159). In addition, Spearman's rank correlation showed a significant negative correlation between percentage of flap necrosis and Laser Index (p value = 0.0083, r -0.83, respectively). Furthermore, significantly higher mean CD31(+) vessel density was detected in the experimental group compared to the control group (p value = 0.0159). Additionally, semi-quantitative image analysis showed lower inflammatory cell count in experimental group compared to control group (p value = 0.0317). In vivo electroporation-mediated IL-10 gene transfer reduced necrosis, enhanced survival and vascularity in the ischemic skin flap.

A common debate among dermatopathologists is that prior knowledge of the clinical picture of melanocytic skin neoplasms may introduce a potential bias in the histopathologic examination. Histologic slides from 99 melanocytic skin neoplasms were circulated among 10 clinical dermatologists, all of them formally trained and board-certified dermatopathologists: 5 dermatopathologists had clinical images available after a 'blind' examination (Group 1); the other 5 had clinical images available before microscopic examination (Group 2). Data from the two groups were compared regarding 'consensus' (a diagnosis in agreement by ≥4 dermatopathologists/group), chance-corrected interobserver agreement (Fleiss' k) and level of diagnostic confidence (LDC: a 1-5 arbitrary scale indicating 'increasing reliability' of any given diagnosis). Compared with Group 1 dermatopathologists, Group 2 achieved a lower number of consensus (84 vs. 90) but a higher k value (0.74 vs. 0.69) and a greater mean LDC value (4.57 vs. 4.32). The same consensus was achieved by the two groups in 81/99 cases. Spitzoid neoplasms were most frequently controversial for both groups. The histopathologic interpretation of melanocytic neoplasms seems to be not biased by the knowledge of the clinical picture before histopathologic examination.

Eosinophil infiltration can be observed in skin disorders, such as allergic/immunologic, autoimmune, infectious, and neoplastic diseases. Clinical presentations are variable and include eczematous, papular, urticarial, bullous, nodular, and fibrotic lesions; pruritus is a common symptom in all. In this review, we present representative eosinophilic skin diseases according to their clinical pattern, together with histologic findings and diagnostic procedures. We also discuss the potential roles of eosinophils in the pathogenesis of dermatologic disorder. Current pathogenesis-based diagnostic and therapeutic approaches are outlined.

Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male-female ratio, 7:5; median age, 61 years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma such as Sezary syndrome or CD30+ T-cell lymphoproliferative disorder. All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs associated with fever. All but one had received a polychemotherapy for an acute myeloid leukemia (n=10) or a urothelial carcinoma (n=1) before the occurrence of the skin eruption. One had an autoimmune lymphoproliferative syndrome causing chronic agranulocytosis requiring granulocyte colony-stimulating factor injection. In all patients, the skin eruption was associated with a slight increase of white blood cell count followed by bone marrow recovery within the next weeks. All skin biopsies showed a dermal perivascular lymphocytic infiltrate containing atypical medium- to large-sized CD3+, CD4+ and CD8+, CD25+, ICOS+, PD1- lymphocytes with a strong CD30 expression in most instances (n=10), suggesting the recruitment of strongly activated T cells in the skin. In 6 patients, a diagnosis of CD30+ lymphoproliferative disorder or Sezary syndrome was proposed or suspected histopathologically, and only the clinical context allowed the diagnosis of ELR with a peculiar presentation with atypical lymphocytes. We describe a series of patients with an unusual form of ELR characterized by the presence of atypical activated T cells in the skin. On a practical ground, pathologists should be aware of this distinctive and misleading presentation.

BACKGROUND Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups. Group a, the control group (n = 5), underwent surgery and received no gene transfer. Group b received electroporation-mediated HGF gene delivery 24 hours after surgery as a treatment. Group c received electroporation-mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5). Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess the efficacy of HGF gene therapy among the groups. RESULTS Electroporation-mediated HGF gene delivery significantly decreased flap necrosis percentage compared with the control group in prophylactic and treatment groups (p = 0.0317 and p = 0.0079, respectively) and significantly increased cutaneous perfusion compared with the control group (p = 0.0317 and p = 0.0159, respectively). Moreover, Spearman rank correlation showed a significant negative correlation between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964, respectively). Furthermore, significantly higher mean CD31 vessel density was detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159, respectively). In addition, quantitative image analysis revealed significantly higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079, respectively). CONCLUSION These findings suggested in vivo electroporation-mediated HGF gene delivery enhanced viability and vascularity of the ischemic skin flap.

BACKGROUND Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. METHODS Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-β, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). RESULTS Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. CONCLUSIONS The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP.