In vivo confocal microscopy: The role of comparative approach in patients with multiple atypical nevi.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) increases diagnostic accuracy for melanoma diagnosis when combined with dermoscopy. In patients with multiple atypical nevi, a comparative dermoscopic approach improves melanoma recognition and saves unnecessary excision. The performance of a comparative approach combining dermoscopy and RCM has not been yet investigated. OBJECTIVE: To validate a comparative dermoscopic + RCM approach according to melanoma diagnostic accuracy in patients with multiple atypical nevi. METHODS: Consecutive patients undergoing RCM examination for ≥3 atypical melanocytic lesions, assessed with a dermoscopic + RCM comparative approach in a real-life setting, from July 2012 to April 2018 at a single centre, were enrolled. Dermoscopic and dermoscopic + RCM morphologic approaches were retrospectively applied by evaluating revisited 7-point checklist, RCM and Delphi scores for each enrolled lesion. Comparative dermoscopic and dermoscopic + RCM approaches were subsequently used. For each approach, lesions were classified as non-suspicious (long-term follow-up) or suspicious (short-term follow-up or excision) and diagnostic accuracy for melanoma diagnosis was assessed. RESULTS: Diagnostic accuracy progressively increased comparing morphologic to comparative approaches, and comparing dermoscopic to dermoscopic + RCM approaches. The retrospective comparative dermoscopic + RCM approach revealed the largest area under the curve (0.84; 95%CI:0.79-0.89; P < .001) and the lowest number needed to excise (5.7). Furthermore, this approach had the highest specificity (67.6%) and sensitivity (100%) levels, which were similar to those verified in the real-life setting. The main study limitations are the retrospective design and high-risk patient inclusion only. CONCLUSIONS: Comparative dermoscopic + RCM approach increases melanoma diagnostic accuracy, reducing unnecessary excision without missing melanomas.

Comparison of two perioperative antibiotic schedules in patients undergoing surgical reconstruction with dermal matrix after excision of skin cancer.

Perioperative antibiotic treatment duration in skin reconstruction with dermal substitutes is not well established. This study compares the incidence of infective complications after two different durations of perioperative antibiotic treatment in patients undergoing surgical reconstruction with skin dermal substitutes (SDS) after excision of skin cancer. Infective complications at the site of SDS were compared in subjects undergoing surgical reconstruction who received either a > 24-hour (extended protocol) or a ≤ 24-hour (short protocol) perioperative antibiotic treatment. Of 116 patients undergoing SDS surgical reconstruction, 62 (53.4%) received an extended schedule, and 54 (46.6%) received a short schedule. The two groups were similar for gender, age, comorbidities, American Society of Anesthesiologists score, and type of skin cancer. Overall incidence rate of infection was 20.7% (24/116). No differences in terms of risk of infection were observed between the two groups (OR: 1.04, 95% CI: 0.42-2.55; P = .937). Patients undergoing SDS reconstruction in the limb/foot had a higher risk of infection in comparison with those undergoing SDS reconstruction in the chest/head (OR: 2.69, 95% CI: 1.06-6.86; P = .038). The short protocol was demonstrated to be beneficial to patients undergoing surgical reconstruction with SDS. A ≤ 24-hour perioperative antibiotic schedule did not increase the infection rate, potentially allowing a reduction of antibiotic exposure.

The influence of MC1R on dermal morphological features of photo-exposed skin in women revealed by reflectance confocal microscopy and optical coherence tomography.

BACKGROUND: The melanocortin 1 receptor (MC1R) gene is one of the major determinants of skin pigmentation. It is a highly polymorphic gene and some of its polymorphisms have been related to specific skin phenotypes, increased risk of skin cancers and skin photoageing. Currently, its contribution to changes in dermal features in photo-exposed skin is unknown. OBJECTIVE: The main objective of this study is to evaluate the potential correlation between MC1R status and specific healthy photo-exposed skin characteristics. MATERIALS AND METHODS: Skin facial features were estimated by evaluation with standard digital photography with automated features count, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in 100 healthy women. Skin of the forearms was used as a control. RESULTS: The study found an association between RHC MC1R polymorphisms and dermal features in photo-exposed areas being represented by increased vessel density and pixel density in OCT (P = .025 and P = .001, respectively) and increased coarse collagen in RCM (P = .034), as compared to non-RHC subjects. To our knowledge this is previously unreported. Additionally, previously reported correlations between light hair colour and pigmented spots with MC1R RHC polymorphisms have been confirmed. CONCLUSIONS: Our results suggest the role of RHC MC1R variants in dermal variations of facial skin, as compared to non-RHC variants. To our knowledge this is previously unreported.

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy.

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already-described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

In vivo assessment of cytological changes by means of reflectance confocal microscopy - demonstration of the effect of topical vitamin E on skin irritation caused by sodium lauryl sulfate.

BACKGROUND: Irritant contact dermatitis is caused by skin barrier damage. Vitamin E is an antioxidant that is commonly used in cosmetics to prevent photo-damage. OBJECTIVES: To show the usefulness of reflectance confocal microscopy in the assessment of irritant skin damage caused by sodium lauryl sulfate (SLS) and of the protective action of vitamin E applied prior to skin irritation. METHODS: Ten healthy volunteers were enrolled. Irritation was induced by the application of a patch test containing SLS 5% aq. for 24 h. Three sites were compared: one site on which a product with vitamin E was applied before SLS treatment, one site on which the same product was applied after SLS treatment, and one control site (SLS only). Each site was evaluated with reflectance confocal microscopy, providing in vivo tissue images at nearly histological resolution. We also performed a computerized analysis of the VivaStack® images. RESULTS: Reflectance confocal microscopy is able to identify signs of skin irritation and the preventive effect of vitamin E application. CONCLUSION: Reflectance confocal microscopy is useful in the objective assessment of irritative skin damage.

Distinct melanoma types based on reflectance confocal microscopy.

Distinct melanoma types exist in relation to patient characteristics, tumor morphology, histopathologic aspects and genetic background. A new diagnostic imaging tool, reflectance confocal microscopy (RCM), allows in vivo analysis of a given lesion with nearly histologic resolution while offering a dynamic view of the tissue in its 'natural' environment. The aim of this study was to analyse cell morphology of consecutive melanomas as they appear on RCM and to correlate morphology with tumor and patient characteristics. One hundred melanomas were visualized by RCM before excision. Clinical data, confocal features and histologic criteria were analysed. Four types of melanomas were identified as follows: (i) Melanomas with a predominantly dendritic cell population ('dendritic-cell melanomas') typically were thin by Breslow index; (ii) Melanomas typified by roundish melanocytes were smaller in size than dendritic cell MMs, but thicker by Breslow index, and predominantly occurred in patients with a high nevus count; (iii) Melanomas characterized by dermal nesting proliferation usually were thick by Breslow index at the time of diagnosis, although frequently smaller in size compared with the other types; and (iv) combined type melanomas may represent an evolution of dendritic cell and/or round cell types. Integration of confocal microscopy with clinical and histologic aspects may help in identifying and managing distinct tumors.

Proposal for an in vivo histopathologic scoring system for skin aging by means of confocal microscopy.

BACKGROUND: Many instrumental devices have been testing in analysing and quantifying the skin aging signs. However, histopathology still remains the only methods that allow a microscopic assessment of the skin. However, a skin biopsy is not feasible in aesthetically critical areas such as the face. Recently, confocal microscopy has been discovered as a noninvasive tool with a nearly histologic resolution. Distinct morphologic confocal aspects on facial skin have been described and correlated with the histopathologic counterparts. OBJECTIVES: In our study we aim to develop an easy to use confocal aging score to quantify the skin aging related signs. METHODS: A sample of facial skin of fifty volunteers has been subjected to confocal imaging. Combining the previously identified confocal features, three different semi-quantitative scores were calculated: - epidermal disarray score (irregular honeycombed pattern + epidermal thickness + furrow pattern); - epidermal hyperplasia score (mottled pigmentation + extent of polycyclic papillary + epidermal thickness; - collagen score (curled fibers, 2 for huddles of collagen, 1 for coarse collagen structures, and 0 for thin reticulated collagen) RESULTS: The epidermal disarray score showed a stable trend up to 65 years and a dramatic increase in the elderly subjects epidermal. Hyperplasia score was characterized by an ascending trend from younger subjects to middle age. The total collagen score showed a progressive trend with age with a different proportion of distinct collagen type. CONCLUSIONS: RCM is a powerful, noninvasive technique that could permit to microscopically quantify the aging signs and to test cosmetic efficacy.

Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy.

Fractionated carbon dioxide (CO2) laser resurfacing is an effective treatment of skin aging. Several studies investigated the morphologic changes due to this laser treatment by using skin biopsies or animal model. Recently, reflectance confocal microscopy (RCM) has emerged as a new tool that can "optically" scan the skin in vivo with a nearly histologic resolution and in a totally noninvasive modality. Our study aims to analyze the skin changes following the ablative fractional CO2 laser sessions by using RCM. Ten patients were subjected to ablative fractional CO2 laser sessions for skin aging. Confocal microscopic images were acquired at baseline (w0), 3 weeks (w3), 6 weeks (w6), and 12 weeks (w12) after laser session. Previously identified confocal parameters were used to assess the skin aging at baseline and after treatment. At w3, the epidermis showed a complete disappearance of the mottled pigmentation upon RCM along with the presence of few Langherans' cells. The collagen type as seen upon RCM observed at baseline was replaced by a newly formed collagen type of long, bright and straight fibers (collagen remodeling). These fibers were parallel arranged and observed throughout the entire RCM mosaic. At w6 and w12 the confocal aspects of the skin was unchanged compared to w3. RCM confirmed the presence of an intense collagen remodeling following laser resurfacing. In line with previous studies, this collagen showed a peculiar arrangement and distribution. The collagen remodeling was still present after 3 months and confirms the long-term effect of the treatment. This is the first time that the skin can be analyzed in vivo at patient's bedside. In the near future, RCM can be an essential adjunct for Clinicians to measure the effects of laser treatment and possibly to gain new insights into the development of side effects.

Early diagnosis of melanoma: what is the impact of dermoscopy?

There are three possible explanations for the improved melanoma recognition when a clinician uses dermoscopy: first, the presence of early dermoscopy signs that become visible in melanoma much before the appearance of the classical clinical features; second, an increased attitude of clinicians to check more closely clinically banal-looking lesions; and third, an improved attitude of clinicians to monitor their patients. In this review, the light and the dark sides of melanoma screening are briefly discussed, including the need to find better strategies to decrease the number of unnecessary excision of benign lesions on one hand, and to finally decrease melanoma mortality rates on the other.

Can noninvasive imaging tools potentially predict the risk of ulceration in invasive melanomas showing blue and black colors?

The aim of this study was to evaluate the reflectance microscopy and histopathologic correlates of dermoscopic blue and black color (BB) in a series of melanomas. We searched our database for dermoscopic images of histopathologically diagnosed pigmented nodular melanomas (pNM), superficial spreading melanomas with a nodular component (SSM+Nod), and melanoma metastasis (METs). All cases were assessed for the presence of dermoscopic BB. Confocal microscopy findings were then compared with those of histopathology. A total of 17 BB-positive tumors including eight pNMs, five SSM+Nod, and four METs were included in the study. We identified two different dermoscopic patterns associated with black color, namely, large black blotches and irregular black dots/globules, which corresponded to two different confocal and histopathologic findings. Black blotches resulted from a total filling of the epidermis by an upward migration of melanocyte nests and pagetoid melanocytes as single cells and clusters, whereas black dots/globules also corresponded to the upward migration of melanocyte nests in the epidermis and pagetoid spread, but with sparing of intervening areas of epidermis. Interestingly, two pNM and two METs showing black color lacked any epidermal involvement and, instead, they were characterized by upward-bulging dermal masses of atypical melanocytes covered by an highly attenuated epidermis. In both cases, black color corresponded to pigment-containing melanocytes in close proximity to the surface of the skin. Our study suggests that black color results not only from epidermal melanin but also from a dense dermal proliferation of pigmented melanocytes under a thinned epidermis. It seems reasonable to suggest that a bulging proliferation of dermal melanocytes beneath a thin epidermal layer could precede ulceration. As ulceration is a very significant prognostic factor, speculation arising from this study that dermoscopic black color may in some cases indicate incipient ulceration is worthy of further study.

Improving triage and management of patients with skin cancer: challenges and considerations for the future.

Skin cancer is the most common malignancy in humans, thus representing a major health concern. Because of the increasing attention to skin cancer prevention, there has been a growing workload for dermatology clinics, with patients referred from primary care requiring assessment of suspicious skin tumors. This places a strain on limited specialist resources and can create a paradoxical situation wherein an early diagnosis becomes increasingly difficult for those patients who actually do suffer from skin cancer. The aim of these recommendations is to propose an updated, rational system of triage, involving improved accuracy of diagnosis and more timely management of skin cancer by both general practitioners and dermatologists.