Effects of Short-Term Moisturizer Application in Different Ethnic Skin Types: Noninvasive Assessment with Optical Coherence Tomography and Reflectance Confocal Microscopy.

BACKGROUND/AIMS: Ethnic skin types are known to differ in their morphological and physiological features. Thus, treatment responses may vary among different races. We aimed to assess skin morphology of different ethnicities and to compare the effect of short-term moisturizer application using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). METHODS: Thirty healthy female subjects of European, Asian and Black ethnicity at 30-45 years of age were included in the study. OCT and RCM imaging was performed on the cheek to compare morphology. Following the 2-week application of a moisturizer cream (Sebamed® lotion) on one forearm, imaging was performed on both forearms to assess and compare treatment responses. RESULTS: Epidermal thickness and morphology of pores varied between the three ethnic groups, with Black subjects displaying the thickest epidermis and largest skin pores. On the treated forearm, OCT measurements revealed a significantly thicker epidermis in all groups as compared to the untreated forearm. Width of skin folds on the treated forearm was measured by RCM to be significantly lower in all ethnic groups as compared to the untreated forearm. CONCLUSION: Different ethnic skin types showed variations in skin morphology and treatment response to short-term moisturizer application. OCT and RCM were useful methods for noninvasive, real-time, repeated assessment of ethnic skin.

Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability.

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma.

The ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) is a novel diagnostic method for fresh tissue examination, which has already shown promising results in the evaluation of healthy skin and different skin tumors. In malignant melanoma, the histological tumor thickness plays an essential role for further treatment strategies. The immediate perioperative measurement of tumor thickness by means of ex-vivo CLSM might accelerate the decision for further operating procedures in malignant melanoma. Ten histologically confirmed malignant melanomas from various donor sites were blindly examined by two investigators via ex-vivo CLSM and conventional light microscopy. The histopathological tumor thickness (HTT) and confocal tumor thickness (CTT) were measured independently and evaluated using correlation curves, Spearman's correlation coefficient, and Bland-Altman plots. Bland-Altman plots for HTT and reflectance-mode CTT, as well as for fluorescence-mode CTT, showed high correlations. Spearman's correlation coefficient of HTT and CTT was 1.00 in FM and RM. The mean difference of RM-CTT and FM-CTT versus HTT was 0.09 ± 0.30 mm and 0.19 ± 0.35 mm. In one case, the HTT was identical to the CTT in both modes. This pilot study shows high conformity of CTT and HTT measured in malignant melanoma underlining the potential of ex-vivo CLSM for perioperative decisions on safety margin excisions of malignant melanoma in the future.

Non-invasive monitoring of subclinical and clinical actinic keratosis of face and scalp under topical treatment with ingenol mebutate gel 150 mcg/g by means of reflectance confocal microscopy and optical coherence tomography: New perspectives and comparison of diagnostic techniques.

Actinic keratosis (AK) corresponds to the earliest stage of in situ squamous cell carcinoma and arises on chronically sun-exposed skin. Around the clinically evident AKs, the apparently healthy epidermis may contain different grades of atypia that can be detected by noninvasive imaging techniques such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). Subclinical actinic keratosis (sAK) has captured increasing interest as a potential target of field therapies. The aim of this study was to evaluate in vivo the changes in the field cancerization undergoing treatment with topical ingenol mebutate by combining RCM and OCT. Twenty patients with field cancerization of the face and scalp were treated with ingenol mebutate gel (150 mcg/g) for three consecutive days on an area of 25 cm2 containing at least two AKs, two sAKs and two apparently healthy sites. About 120 lesions were evaluated through clinical investigation and clinical, dermoscopical, RCM and OCT images at day 0, 4, 14 and 56 based on the diagnostic criteria for AKs. Main pathological features improved in both AKs and sAKs, in particular the epidermal thickness measured by OCT and the epidermal atypia graded by RCM. Local skin reactions (LSR) arose predominantly in the lesional area compared with healthy skin. A complete clearance was detected in 58% for AKs, and in 55% and 72% for sAKs measured by RCM and OCT, respectively. Both OCT and RCM allow the morphological representation of field cancerization including subclinical lesions and provide complementary information. Ingenol mebutate is effective not only in clinically evident but also in sAKs. The differences in LSR highlight the potential selectivity of the treatment.

Patient Attitude towards Videodermatoscopy for the Detection of Skin Cancer: A Cross-Sectional Study.

BACKGROUND: Videodermatoscopy (VD) is a useful device for supporting dermatologists in the distinction between benign and malignant lesions. However, only few patients have access to VD in daily practice. OBJECTIVES: To investigate patient attitudes towards VD. METHOD: A cross-sectional study was conducted between May and June 2018. Patients were asked to complete a self-administered questionnaire on the popularity of VD. Descriptive analysis was performed including contingency tables and χ2 tests to investigate associations between sociodemographic data and the popularity of VD. RESULTS: A total of 61.2% (123/201) of the patients had not heard of VD at the time of assessment or were unsure. Of the 38.8% of patients (78/201) who already knew of VD, 64.1% (50/78) reported that they had already been investigated by VD; 57.5% (111/193) were willing to pay an extra fee for VD. A high level of education and private insurance status had a statistically significant association with the popularity of VD (p = 0.036 and p = 0.026, respectively). CONCLUSIONS: There was a strong information deficit, especially in patients with lower education and statutory health insurance. Nevertheless, the willingness to pay an extra fee for a VD-assisted skin examination was high. Dermatologists should actively offer and inform their patients about VD when performing skin cancer screening.

Successful Treatment of Genital Warts with Ingenol Mebutate Monitored with Optical Coherence Tomography and Reflectance Confocal Microscopy.

Ingenol mebutate (IM) is approved for the treatment of actinic keratosis and induces cell death in precancerous lesions. The efficacy of IM in the treatment of genital warts was investigated in a therapy-refractory patient. The 74-year-old male was treated with IM gel for three consecutive days. Treatment course and efficacy were evaluated by clinical inspection and non-invasive diagnostics namely optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Within 24 to 48 hours IM induced a strong local inflammatory reaction. One week later a complete response was observed. OCT and RCM showed a strong reaction after treatment with erosions, swelling of cells, and a subepidermal dark band in representative lesions. IM has the advantage of a short treatment period in contrast to other topical treatments and shows a promising clinical outcome. Larger studies are needed to validate the data.

Simple 3-criteria-based ex vivo confocal diagnosis of basal cell carcinoma.

BACKGROUND: Fast and simple microscopic evaluation of basal cell carcinoma (BCC) together with its subtype determination would accelerate diagnostic and therapeutic procedures in dermatology including Mohs surgery. OBJECTIVES: Assessing whether simplified 3-criteria-based ex vivo confocal microscopic (CM) examination can reliably predict BCC diagnosis and subtype. Analyzing interobserver agreement between expert and novice examiner. METHODS: CM images of 235 skin samples from 150 patients were prospectively evaluated by 2 blinded examiners for the presence of 3 predefined BCC criteria namely presence of tumor mass, peripheral palisading and clefting. RESULTS: Out of 235 skin samples 116 showed histological presence of BCC, confocally expert diagnosed a BCC in 110 and novice examiner in 107 samples. The overall sensitivity and specificity of detecting residual BCC was 96.6% and 98.7%, respectively. Confocally, examiners diagnosed correctly nodular BCC in 96.6%, respectively, 98.3%, superficial BCC in 96.8%, respectively, 93.5%, infiltrating BCC in 88.9%, respectively, 83.3% and other BCC subtype in 22.2%, respectively, 0% (expert and novice examiner, respectively). CONCLUSION: Ex vivo CM allowed intraoperative examination of BCC based on only 3-criteria with high sensitivity and specificity, provided useful information on tumor subtype and showed that both experienced and non-experienced examiners may use this diagnostic approach with excellent results.

Ex vivo confocal microscopy features of cutaneous squamous cell carcinoma.

BACKGROUND: Rapid microscopic evaluation of cutaneous squamous cell carcinoma (SCC), its grade of differentiation and level of invasiveness would enable better management of patients' therapy. OBJECTIVES: Analyzing specific ex vivo confocal microscopy criteria whether they can predict diagnosis of invasive SCC vs carcinoma in situ and poorly differentiated or undifferentiated vs well and moderately differentiated SCC. METHODS: Ex vivo confocal images of 102 SCCs in 57 patients were evaluated immediately after excision for the presence of predefined criteria based on confocal and histological knowledge. RESULTS: In histopathological examination, 30 SCCs were in situ and 72 invasive. Of these, 29 invasive SCC tumors were well, 19 moderately, 15 poorly differentiated and 9 undifferentiated. χ2 analysis demonstrated that presence of erosion/ulceration, plump bright or speckled cells in dermis, keratin pearls and peritumoral inflammatory infiltrate correlated with diagnosis of invasive SCC. Erosion/ulceration and peritumoral inflammatory infiltrate were observed more frequently in poorly differentiated or undifferentiated tumors. Plump bright or speckled cells in the dermis were observed less often in well-differentiated tumors. The presence of keratin pearls was associated with well or moderately differentiated tumors. CONCLUSION: Ex vivo CLSM allowed rapid examination of SCC and provided useful information on invasiveness and grading of the tumor.

Immunofluorescence and confocal microscopy for ex-vivo diagnosis of melanocytic and non-melanocytic skin tumors: A pilot study.

BACKGROUND: Ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) offers rapid examination of freshly excised tissue. During the conventional examination immunohistochemistry enables to distinguish various cell types. The possibility of immunofluorescent techniques could enhance the accuracy of the diagnosis performed by ex-vivo CLSM. METHODS: The tissue probes from various skin tumors were stained with FITC-labeled S-100A10, Melan-A and anti-Ber-EP4 antibodies before examination with ex-vivo CLSM in the fluorescence and reflectance modes. Results were compared to negative controls and conventional histopathology. The staining protocols were evaluated by establishing a scoring system according to the signal intensity found in ex-vivo CLSM. RESULTS: S100 immunostaining was successful in 55.6%. Dilution of 1:200 resulted in the best possible evaluation of the tumor. The best suitable protocol was protocol B (phosphate buffered saline [PBS], without blocking agent). Melan A immunostaining was positive in 66.7%, the best dilution was 1:500 and protocol B (PBS, without blocking agent) was the most suitable. Ber-EP4 immunostaining presented a signal in 85.7%, the best dilutions were 1:200 and 1:500 and protocol A (PBS, with blocking agent) showed most optimal results. CONCLUSION: The use of fluorescent-labeled antibodies in ex-vivo CLSM is possible and could improve intraoperative diagnostics of skin tumors.