The value of reflectance confocal microscopy in diagnosis of flat pigmented facial lesions: a prospective study.

BACKGROUND: Flat pigmented facial lesions are difficult to diagnose even with dermatoscopy. It is controversial how additional information obtained by in vivo reflectance confocal microscopy (RCM) impacts the diagnosis and management. OBJECTIVE: To examine what in vivo reflectance confocal microscopy of flat pigmented facial lesions adds to clinical examination using dermatoscopy including digital dermatoscopic monitoring. METHODS: We prospectively collected 70 cases of flat pigmented facial lesions and recorded diagnoses and management decisions by experts based on direct clinical examination aided by dermatoscopy including digital dermatoscopic monitoring and by remote experts who reviewed the corresponding confocal images. The expert confocal readers were blinded to the clinical and dermatoscopic appearance of the lesion. RESULTS: The sensitivity of dermatoscopy plus digital dermatoscopic monitoring was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 84.0% (95% CI 70.89% to 92.83%). The sensitivity of RCM was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 82.0% (95% CI 68.56% to 91.42%). CONCLUSION: Although most flat pigmented facial lesions can be managed by clinical examination and dermatoscopy alone, confocal microscopy is a useful adjunct in selected lesions. If RCM is not correlated with clinical and dermatoscopic information, there is risk of overdiagnosis of actinic keratosis, however.

UV-induced alterations of the skin evaluated over time by reflectance confocal microscopy.

BACKGROUND: Ultraviolet radiation (UVR) induces various alterations of the skin and plays a decisive part regarding the development of melanoma and non-melanoma skin cancer. For a closer examination of these phenomena in vivo reflectance confocal microscopy (RCM) is one of the most eligible options as it represents a diagnostic tool that allows a non-invasive examination of the skin, showing microanatomical structures and individual cells. OBJECTIVES: The aim of this study was using RCM to observe alterations of the skin induced by UVR and to describe the development of these changes. In addition, the findings were compared with histological examinations of the same area. METHODS: A small area in the gluteal region of 10 healthy subjects was exposed to a threefold individual minimal erythema dose of solar-simulated UVR. The following development of the sunburn reaction was evaluated with RCM 1, 24, 72 h and 1 week after UVR exposure. Furthermore, RCM images of unexposed skin were obtained, serving as a reference. To contrast histological examination with RCM, punch biopsies were performed at each point in time. The obtained data were interpreted regarding histological and RCM-based criteria on sunburn reaction. RESULTS: All important UVR-induced alterations of the skin could be shown in RCM beginning with an inflammatory reaction (inflammatory cells, vasodilatation, oedema), containing the formation of microvesicles, followed by the appearance of apoptotic keratinocytes (sunburn cells), activated melanocytes and at last, loss of the epidermal structure. There was an excellent correlation between RCM and histological features. CONCLUSIONS: Reflectance confocal microscopy is a highly valuable tool for non-invasive monitoring of UVR-induced changes of the skin over time. Furthermore, RCM provides a more detailed visualization of inflammatory cell formation and epidermal blood flow than histological examination can.

Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.

Patient acceptance and diagnostic utility of automated digital image analysis of pigmented skin lesions.

BACKGROUND: Computerized analysis of pigmented skin lesions may help to increase diagnostic accuracy for melanoma, help to avoid unnecessary procedures and reduce health care costs. OBJECTIVES: We evaluated both the patient acceptance and diagnostic utility of such an analysis tool in a real clinical setting. METHODS: Two hundred nine consecutive patients (median age: 34 years, range: 2-73 years), who were concerned about a pigmented skin lesion, answered a questionnaire about their attitude towards computerized analysis and their confidence in the resulting findings. Using a dermoscopy analyser, their skin lesions (n = 219) were then grouped into the categories, benign, suspicious and malignant, and results were compared with those obtained by in-person examination of dermato-oncologic experts. RESULTS: More than half of the patients (n = 114) would accept the use of computer analysis for melanoma screening; although 16 (14.0%) patients would accept this method solely, 98 (86.0%) patients would prefer an additional in-person examination by a dermatologist. Of the 219 pigmented skin lesions, the dermoscopic experts rated 171 (78.1%) as benign, 36 (16.4%) as suspicious and 12 (5.5%) as malignant, whereas computer analysis revealed 102 (46.6%) benign, 78 (35.6%) suspicious and 39 (17.8%) malignant lesions. At the expense of specificity (48.8%), the sensitivity of computerized analysis was excellent (100%) and equal to that of in-person examination. CONCLUSIONS: Most patients would accept computer analysis for melanoma screening, some of them even without reservations. However, due to a high rate of false positive computer assessments, it cannot be recommended as a screening tool at this time.

Autoimmune bullous diseases in Austria.

Autoimmune bullous diseases (AIBD) are chronic disorders associated with significant morbidity and even mortality, for which the 19 dermatologic departments in Austria apply standard modalities to provide state-of-the-art diagnosis and treatment. Most of the affected individuals are initially treated on an inpatient basis, with follow-up done in specialized outpatient clinics or in private practices. A well-established system of care for AIBD patients is thus available nationwide. Considering the significant morbidity and mortality but also rareness of AIBD, national and international standardization of AIBD administration in registries is a major requirement of further improvement in patient care.

In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. OBJECTIVES: In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. METHODS: Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). RESULTS: The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 ± 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 ± 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). CONCLUSIONS: The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening.

Follow-up of actinic keratoses after shave biopsy by in-vivo reflectance confocal microscopy--a pilot study.

BACKGROUND: Monitoring of treatment efficacy after shave biopsy of actinic keratoses (AK) is often difficult, as clinical and dermoscopic features may not be reliable. OBJECTIVES: We investigated the applicability of in-vivo reflectance confocal microscopy (RCM) for the follow-up of AK after shave biopsy. METHODS: A total of 10 lesions were investigated by RCM before shave biopsy, after 3 and 12 months by two observers in agreement blinded to location, patients and time interval. RESULTS: At baseline all lesions showed typical clinical, dermoscopic and RCM criteria of AK. Three months after shave biopsy, all lesions presented clinically as normal skin (NS), but two lesions showed features suspicious for AK by RCM. After 12 months, one lesion of these two lesions changed into NS in RCM, whereas the other lesion progressed into clinical visible AK. At baseline, the two observers diagnosed 10 of 10 lesions correctly in RCM, after 3 months eight of 10 lesions and after 12 months all lesions were diagnosed correctly. CONCLUSIONS: Our results suggest that RCM might be a useful tool in the follow-up of AK after shave biopsy and might be used in inconclusive clinical and dermoscopic presentations of lesions after surgery or other treatment modalities.

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

BACKGROUND: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level. OBJECTIVES: To assess cytomorphological and architectural RCM features of facial LM/LMM. METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM. RESULTS: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed. CONCLUSIONS: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

Frequency, clinical and dermoscopic features of benign papillomatous melanocytic naevi (Unna type).

BACKGROUND: Most previous studies on melanocytic naevi have not distinguished between the different types of naevi, except for some studies trying to define atypical naevi. No large, population-based studies on papillomatous or Unna-type melanocytic naevi have been performed. OBJECTIVES: To investigate the dermoscopic and clinical features of papillomatous naevi and to study some of the factors which could potentially influence their development. METHODS: Seven hundred and seven caucasians aged 1-82 years participated in a screening campaign at open-air recreation facilities in Austria. The volunteers underwent a total body examination by experienced dermatologists and answered a questionnaire. Clinical and dermoscopic images of one representative papillomatous naevus per person were taken. RESULTS: Twenty-nine per cent of the volunteers exhibited papillomatous naevi, the highest frequency being found in young adults. No correlation between the frequency of papillomatous naevi and gender, skin type, sunburns, sunbed use or hormonal factors was found. Most lesions were brown papules (median diameter 5.0 mm), located on the trunk. Dermoscopy showed a predominance of homogeneous and globular pattern, multifocal hypo/hyperpigmentation and comma vessels. Of the papillomatous naevi, 9.8% showed suspicious scores with dermoscopic algorithms. CONCLUSIONS: The lack of exogenous influencing factors and the predominance of globular dermoscopic pattern strengthen the hypothesis that papillomatous naevi belong to the same spectrum as small congenital melanocytic naevi. As the role of papillomatous naevi as precursors of melanoma remains unclear and they are frequently not recognized by the patients, one should perform dermoscopy of papillomatous naevi during skin cancer screening.

In vivo confocal scanning laser microscopy of common naevi with globular, homogeneous and reticular pattern in dermoscopy.

BACKGROUND: A systematic examination and comparison of confocal scanning laser microscopy (CSLM) features of benign naevi showing different dermoscopic patterns has never been performed. OBJECTIVES: Systematically to assess CSLM features of dermoscopically benign reticular, globular and homogeneous naevi and to correlate CSLM findings with dermoscopy and histopathology. METHODS: CSLM was performed on 30 naevi in 29 patients including 10 reticular, 10 globular and 10 homogeneous naevi showing a uniform pigmentation pattern with dermoscopy. Cytomorphological and architectural features of each naevus were assessed and distinct characteristics for each group of naevi were defined. CSLM features were correlated with the histopathological findings and their applicability for the diagnosis of naevi with different dermoscopic patterns was assessed by two blinded observers. RESULTS: A correct diagnosis was made in 26 and 28 of 30 cases, respectively, by two blinded observers using previously defined CSLM features. Well-defined melanocytic caps, well-defined edged papillae and black papillae concurrently with the absence of white papillae were found in all reticular naevi (10 of 10). Numerous, large junctional/dermal melanocytic nests (10 of 10), ill-defined edged papillae (eight of 10) and white papillae (nine of 10) were found in globular naevi. Homogeneous naevi showed an intermediate pattern between reticular and globular naevi: ill-defined edged papillae (10 of 10), black and white papillae within the same naevus (eight of 10) and junctional/dermal melanocytic nests (three of 10) were seen. CONCLUSIONS: Different dermoscopic patterns of benign naevi are reflected in different architectural features in CSLM. As benign naevi show a regular architecture of monomorphous melanocytes in contrast to melanomas, similar dermoscopic features of naevi and early melanomas may be differentiated by CSLM.

In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images.

BACKGROUND: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasi-histopathological' resolution viewing microanatomical structures and individual cells. OBJECTIVES: To validate diagnostic confocal examination of melanocytic skin tumours using unselected tumour images. METHODS: In the present study, we used a total of 3709 unselected CLSM tumour images obtained from 20 malignant melanomas and 50 benign naevi. The entire set of images derived from each tumour was evaluated by independent observers. Classification tree analysis based on a subsample of 857 tumour images was performed to develop a diagnostic algorithm. RESULTS: Overall, sensitivity and specificity of 97.5% and 99% could be achieved by the independent observers (positive predictive value 97.5%, negative predictive value 99%). Classification tree analysis yielded a three-step algorithm based on only three morphological CLSM features, facilitating a correct classification in 92.4% of the benign naevus images and 97.6% of melanoma images. CONCLUSIONS: 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.