In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the examination of skin morphology in real time at a resolution equal to that of conventional microscopes. The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of benign nevi and melanoma. five independent observers without previous experience in CLSM received a standardized instruction about diagnostic CLSM features. Subsequently, 117 melanocytic skin tumors (90 benign nevi and 27 melanoma), imaged using a commercially available, near-infrared, reflectance confocal laser scanning microscope, were evaluated by each observer. Overall, sensitivity of 88.15% and specificity of 97.60% was achieved by the five observers. Logistic regression analysis revealed that mainly cytomorphology, architecture and keratinocyte cell borders should be taken into account for diagnostic decisions. Remarkably, using the presence or absence of monomorphic melanocytes as a single diagnostic criterion, the classification results with a sensitivity of 98.15% and a specificity of 98.89% were superior to the intuitive, integrative judgement of the observers. This first sensitivity and specificity study with CLSM has yielded promising results. CLSM provides new and useful information to the clinician diagnosing melanocytic skin tumors.

BACKGROUND Melanoma and nonmelanoma skin cancer are the most frequent malignant tumors by far among whites. Currently, early diagnosis is the most efficient method for preventing a fatal outcome. In vivo confocal laser‐scanning microscopy (CLSM) is a recently developed potential diagnostic tool. METHODS One hundred seventeen melanocytic skin lesions and 45 nonmelanocytic skin lesions (90 benign nevi, 27 malignant melanomas, 15 basal cell carcinomas, and 30 seborrheic keratoses) were sampled consecutively and were examined using proprietary CLSM equipment. Stored images were rated by 4 independent observers. RESULTS Differentiation between melanoma and all other lesions based solely on CLSM examination was achieved with a positive predictive value of 94.22%. Malignant lesions (melanoma and basal cell carcinoma) as a group were diagnosed with a positive predictive value of 96.34%. Assessment of distinct CLSM features showed a strong interobserver correlation (κ >0.80 for 11 of 13 criteria). Classification and regression tree analysis yielded a 3‐step algorithm based on only 3 criteria, facilitating a correct classification in 96.30% of melanomas, 98.89% of benign nevi, and 100% of basal cell carcinomas and seborrheic keratoses. CONCLUSIONS In vivo CLSM examination appeared to be a promising method for the noninvasive assessment of melanoma and nonmelanoma skin tumors. Cancer 2006. © 2006 American Cancer Society.

These results indicate that TLR9-targeted therapy can stimulate innate immune responses in cancer patients, identify biomarkers that may be associated with TLR9-induced tumor regression, and encourage the design of follow-up studies to evaluate the ability of this therapeutic approach to target human cancer.

Reflectance confocal microscopy examination appears to be a promising method for non-invasive assessment of erythematosquamous skin diseases. This study provides a set of well-described morphological criteria with obvious diagnostic impact, which should be used in further investigations.

We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

This study provides a set of morphologic confocal microscopy criteria showing promise as a noninvasive monitoring tool in the treatment of actinic keratoses.

In vivo CLSM augurs a sea change in the way we will view skin tumour processes clinically at the bedside and merits application for use as a screening tool in skin oncology.

Reflectance confocal microscopy (RCM) enables in vivo imaging of human skin at a quasi histologic resolution. The black-and-white RCM images show horizontal sections of the skin, at a maximum depth of 350 microm. To date, the RCM features of a significant number of skin conditions have been described. The main focus of the research community investigating RCM, however, lies on describing and diagnosing melanocytic skin lesions. Taking into account all RCM studies dealing with diagnostic accuracy in melanocytic skin lesions, sensitivity and specificity of approximately 90% and 86% could be found. Improvement of diagnostic accuracy, improved assessment of dermoscopic-histologic correlation, in vivo biopsy side selection, surgical margin assessment, and response control of conservative therapies in skin diseases are some of the major advantages of this novel imaging method. Additionally, RCM holds inherent potential for teledermatologic application and automated image analyzing. This article describes morphologic features of diverse skin lesions and features of "normal skin," summarizes diagnostic advances of RCM, compares studies dealing with diagnostic applicability, and discusses further research goals of this exciting new imaging technique.