Is a single day patient friendly methyl aminolevulinate photodynamic therapy illumination scheme for superficial basal cell carcinoma feasible? A randomized multicenter pilot trial.

BACKGROUND: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) is highly effective for the treatment of superficial basal cell carcinoma (sBCC). Current European treatment protocol requires two hospital visits, which is costly and unpractical. The aim of this study was to evaluate the efficacy of fractionated MAL-PDT, using two light fractions at 3 and 4 h compared to illumination at 3 and 5 h after MAL-application. METHODS: Thirty patients were randomized into two groups. The first group received illumination at 3 and 4 h (20 + 55 J/cm2) after MAL-application (3/4 group). In the other group, two light fractions were performed at 3 and 5 h (20 + 55 J/cm2) after MAL-application (3/5 group). The lesion response was evaluated at 3 and 12 months posttreatment. RESULTS: In the 3/5 group, 70.0% showed a complete response (CR) at 3 months compared to 63.6% in the other group. At 12 months, 100% showed a CR in the 3/5 group compared to 80.0% in the other group. However, most failures/recurrences were eventually due to the presence of a more aggressive BCC subtype, mostly caused by sampling error of the primary punch biopsy. CONCLUSION: Single day protocol for MAL-PDT for sBCC is feasible and this study shows promising results.

A four-phase strategy for the implementation of reflectance confocal microscopy in dermatology.

BACKGROUND: Reflectance confocal microscopy (RCM) is gradually implemented in dermatology. Strategies for further implementation and practical 'hands on' guidelines are lacking. OBJECTIVE: The primary outcome was to conduct a general strategy for further implementation of RCM. The secondary outcome was the diagnosis of psoriasis and differentiation of stable from unstable psoriatic plaques by means of the 'hands on' protocol, derived from the strategy. METHODS: We used a four-phased model; an exploring phase, a systematic literature search, a clinical approach and, finally, an integration phase to develop a clinical guideline for RCM in psoriasis. Receiver operating characteristic curve statistics was applied to define the accuracy for the diagnosis of unstable psoriasis. RESULTS: A general strategy for further implementation of RCM and practical approach was developed to examine psoriasis by RCM and to distinguish stable from unstable psoriasis. Unstable psoriasis was diagnosed by epidermal inflammatory cell counts with a sensitivity and specificity of 91.7% and 98.3%, respectively, and with an accuracy of 0.92 (area under the curve). In addition, a monitoring model was proposed. CONCLUSION: This is the first study that shows a method for implementation of RCM in dermatology. The strategy and hands on protocol for psoriasis may serve as a model for other dermatological entities and additionally may lead to specialized ready-to-use RCM protocols for clinical dermatological practice.

Reflectance confocal microscopy: non-invasive distinction between actinic keratosis and squamous cell carcinoma.

BACKGROUND: Early recognition of squamous cell carcinoma (SCC) is difficult. Non-invasive reflectance confocal microscopic (RCM) imaging of the skin is a promising diagnostic technique. Although several RCM features for SCC and AK have been described, it is not determined whether RCM has the ability to distinguish between SCC and actinic keratosis (AK). OBJECTIVE: To determine in vivo reflectance confocal microscopic features that are specific for making a distinction between AK and SCC. METHODS: In 24 patients, 30 lesions clinically suspicious for AK or SCC were selected for RCM imaging. Following the imaging procedure, a 3 mm skin biopsy was obtained for confirmation of the histopathological diagnosis. Two observers evaluated the RCM images according to a literature based list of RCM features. The obtained data were evaluated by an univariate and forward multivariate logistic regression analysis, kappa analysis and independent T-test. RESULTS: The univariate logistic regression showed statistically significant odds ratios for several RCM features, including architectural disarray in the stratum granulosum, architectural disarray in the spinous layer and nest-like structures in the dermis. The forward multivariate logistic regression analysis showed that the combination of these features increased the ability to make the correct diagnosis AK and SCC non-invasively. The interobserver agreement between a starting and an experienced RCM observer ranged from poor to no agreement. CONCLUSION: This study revealed specific RCM features that can distinguish between AK and SCC, stimulating further prospective, large cohort research in this field. This will result in correct, efficient and adequate diagnosis and treatment of clinically difficult to distinguish AK and SCC lesions.

Prospective differentiation of clinically difficult to distinguish nodular basal cell carcinomas and intradermal nevi by non-invasive Reflectance Confocal Microscopy: a case series study.

BACKGROUND: Clinical differentiation between a nodular basal cell carcinoma (nBCC) and a benign intradermal nevus can be difficult. Even with additional dermoscopic evaluation, a correct diagnosis may be difficult. Currently, histopathological examination of a biopsy is the gold standard to differentiate between these lesions. However, this is an invasive technique and sampling errors can occur. In vivo Reflectance Confocal Microscopy (RCM) is a non-invasive technique to evaluate a skin lesion at a microscopic level. RCM features of nBCCs and intradermal nevi have been described in research setting. However, the use of RCM for prospective differentiation between difficult to diagnose nodules into nBCCs and intradermal nevi in clinical practice has not been demonstrated yet. OBJECTIVE: In this study, we aim to address a common clinical scenario; to differentiate clinically and dermoscopically difficult to distinguish nodules, into nBCCs and intradermal nevi by RCM. MATERIAL AND METHODS: Six patients with clinically and dermoscopically difficult to distinguish nodular skin lesions were evaluated by RCM to differentiate prospectively between nBCCs and intradermal nevi. In five out of six cases, a 3 mm punch biopsy was obtained to confirm the RCM diagnosis. RESULTS: Observed RCM features that allowed differentiation between nBCCs and intradermal nevi were the dermal-epidermal junction patterns, the appearance of the nests and the degree of vascularization. CONCLUSIONS: This case series study demonstrates the value of non-invasive in vivo RCM imaging in routine patient care, with respect to the prospective diagnosis of clinically difficult to distinguish nBCCs and intradermal nevi. Subsequently, biopsies of benign lesions in cosmetic areas could be avoided.

The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: a systematic review.

In vivo examination of the skin by reflectance confocal microscopy (RCM) has been performed for about 20 years, leading to a broad spectrum of imaged infectious and inflammatory skin diseases (ISD) with many described RCM features. We systematically reviewed all available literature concerning ISD evaluated by RCM. Furthermore, we assessed the accuracy of the features and defined recommendations for future studies after indicating the limitations in the current published literature. PubMed, Embase, Cochrane Library and Web of Science databases were searched for literature. All studies on RCM and ISD were reviewed and quality assessment was determined by using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The literature search revealed 77 eligible studies for inclusion. Different RCM features in a broad spectrum of ISD have been described. Further, RCM has been used for monitoring treatment and evolution of ISD, as well as for diagnostic purposes. This systematic review provides an overview of the broad spectrum of ISD imaged by RCM. Although RCM seems to be a promising monitoring and diagnostic tool for ISD, studies with appropriate methodological quality are necessary to create adequate guidelines and protocols for further implementation of RCM in clinical practice.