Artificial intelligence algorithms and 3D volumetric rendering for basal cell carcinoma detection and tumor depth assessment in RCM-OCT images: a pilot study.

The Reflectance Confocal Microscopy - Optical Coherence Tomography (RCM-OCT) device has shown utility in detecting and assessing depth of basal cell carcinoma (BCC) in vivo but is challenging for novices to interpret. Artificial intelligence (AI) applied to RCM-OCT could aid readers. We trained artificial intelligence (AI) models, using OCT rasters of biopsy-confirmed BCC, to detect and create 3D BCC rendering and automatically measure tumor depth. Trained AI models were applied to a separate test set containing rasters of BCC, benign lesions, and normal skin. Blinded reader analysis and tumor depth correlation with histopathology were conducted. BCC detection improved from viewing OCT rasters only (sensitivity 73.3%, specificity 45.5%) to viewing rasters with AI-generated BCC rendering (sensitivity 86.7%, specificity 48.5%). A Pearson Correlation r2 = 0.59 (p=0.02) was achieved for the tumor depth measurement between AI and histologic measured depths. Thus, addition of AI to the RCM-OCT device may expand its utility widely.

Dynamic Optical Coherence Tomography of Blood Vessels in Cutaneous Melanoma-Correlation with Histology, Immunohistochemistry and Dermoscopy.

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery.

Dynamic Optical Coherence Tomography: A Non-Invasive Imaging Tool for the Distinction of Nevi and Melanomas.

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted.

Visible characteristics and structural modifications relating to enlarged facial pores.

BACKGROUND: Many factors relate to enlargement and visibility of facial pores. However, how enlargement relates to modification of the skin structure is still poorly analysed. Therefore, our aim was to characterise the visible features and the micro-environment of facial pores. MATERIALS AND METHODS: We recruited 160 women, half of them with normal-size facial pores, the other half presenting enlarged pores. We analysed their right cheek using standardised photography, in vivo reflectance microscopy and optical coherence tomography. RESULTS: If the area of pores is indeed the most differentiating visible characteristic, enlarged facial pores are also denser and more contrasted. At the structural level, enlarged facial pores present a more regular organisation of keratinocytes, an irregular dermo-epidermal junction and a higher attenuation of collagen between the surface and deeper layers. Still, the most relevant alterations of enlarged facial pores are the presence of bright tubular structures surrounding hair follicles and enlarged hair shafts. CONCLUSION: These observations suggest that alterations of the stroma could result in altered skin tensions, leading to the dilation of the infundibulum and enlarged hair shaft. The modified tension would also explain the more regular organisation of the keratinocytes and the irregular dermo-epidermal junction.

Reflectance confocal microscopy in actinic keratosis-Comparison of efficacy between cryotherapy protocols.

BACKGROUND: Actinic keratosis (AK) incidence is increasing. Due to the risk of progression to squamous cell carcinoma, early detection and treatment are essential. The method stated in the European Consensus is cryotherapy, but there is no standard protocol defined for better results. OBJECTIVES: To compare two different cryotherapy protocols for AK using reflectance confocal microscopy (RCM) as a noninvasive imaging method for evaluation. METHODS: A self-controlled clinical trial was proposed to compare the efficacy of cryotherapy in two different application protocols. Grade II AKs in the forearms were submitted to freezing and thawing time of 10 seconds for 1 cycle (group A) or 2 cycles (group B). At baseline and 4 weeks after treatment, the same dermatologists assessed RCM evaluation (thickness of horny layer, parakeratosis, dyskeratosis, atypia in spinous layer, fibrosis, and presence of inflammatory cells in epidermis and dermis). RESULTS: We examined 24 AK lesions in each group. Statistical evaluation of the results evidenced superior response after 2 cycles of cryotherapy in parakeratosis and number of inflammatory cells in epidermis. CONCLUSION: Both protocols are effective in clearing clinical AK. Two cycles are not generating more side effects (fibrosis) and could reduce the risk of recurrence (better "clearance" of parakeratosis).

Concordance among in vivo reflectance confocal microscopy, trichoscopy, and histopathology in the evaluation of scalp discoid lupus.

BACKGROUND: Reflectance confocal microscopy (RCM) has been used for the evaluation of several inflammatory skin conditions, including skin discoid lupus erythematosus (DLE), and has been correlated with conventional histopathology (HP). However, RCM is not being widely used in trichology. Few reports and just preliminary data suggest the use of RCM as a complementary tool in alopecias. OBJECTIVES: To correlate the major RCM features of scalp DLE with trichoscopy and HP findings of biopsy specimens obtained from the same lesions. METHODS: This is an observational, analytical, and cross-sectional study involving 12 patients with a clinically established diagnosis of scalp DLE. Patients underwent global clinical photograph, trichoscopy, and RCM examination in the same site followed by two 4-mm punch biopsy specimens for HP analysis. Inter-methods agreement among RCM imaging, trichoscopy, and horizontal histopathology sections (HHS) were calculated using Cohen Kappa (k) statistics. RESULTS: Statistical analysis of the agreement between RCM and HP features disclosed an overall agreement similar to skin DLE. Seven of the eleven features evaluated had agreement superior to 75%. We also evaluated RCM features associated with three of their corresponding trichoscopic findings for further investigation of their agreement with HP. Statistical analysis showed an enhancement with agreement of 86% when the non-invasive techniques are used together. CONCLUSION: Consistent correlation between RCM and HP observed in our study supports the reliability of RCM in the diagnosis of scalp DLE. RCM may be considered a promising tool for scalp DLE microscopic evaluation and presents similar RCM features to DLE in other body sites. By associating clinical, trichoscopic and RCM evaluation, dermatologists will have a non-invasive arsenal for the assessment of hair and scalp disorders, benefiting patients.

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.

Reflectance confocal microscopy made easy: The 4 must-know key features for the diagnosis of melanoma and nonmelanoma skin cancers.

BACKGROUND: Reflectance confocal microscopy (RCM)-based skin cancer diagnosis requires proficiency. OBJECTIVE: To identify a short list of key RCM features of skin cancers and test their diagnostic utility. METHODS: We identified key RCM features through consensus among 6 experts using a modified Delphi method. To test the diagnostic utility of these RCM key features, 10 novice RCM readers evaluated a subset of 100 RCM cases from a retrospective data set of benign and malignant skin neoplasms. RESULTS: From 56 features reported in the literature, the experts identified 18 RCM features as highly valuable for skin cancer diagnosis. On the basis of consensus definitions, these RCM features were further clustered into 2 melanoma-specific key features (atypical cells and dermoepidermal junction disarray), 1 basal cell carcinoma-specific key feature (basaloid cords/islands), and 1 squamous cell carcinoma-specific key feature (keratinocyte disarray). The novice reading study showed that the presence of at least 1 of the 4 key features was associated with an overall sensitivity for skin cancer diagnosis of 91%, with a sensitivity for melanoma of 93%, a sensitivity for basal cell carcinoma of 92%, and a sensitivity for squamous cell carcinoma of 67%, and an overall specificity of 57%. LIMITATIONS: The consensus was based on only six RCM experts and the validation study was retrospective. CONCLUSIONS: A consensus terminology short list identifying the 4 RCM key features for skin cancer diagnosis may facilitate dissemination of RCM to novice users.

Reflectance confocal microscopy features of thin versus thick melanomas.

BACKGROUND: In-vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1 mm according to Breslow index) versus thick (>1mm) melanomas. METHODS: Thirty patients with histopathologically confirmed cutaneous melanoma were included in the study. RCM was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤1 mm) and 15 were thick (Breslow thickness >1 mm). RESULTS: In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs. 0%, P=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs. 6.7%, P=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs. 40%, P=0.001), non-edged papillae (100% vs. 60%, P=0.006), numerous pagetoid cells (73.3% vs. 33.3%, P=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs. 20%, P=0.058) and epidermal disarray (93.3% vs. 66.7%, P=0.068). CONCLUSIONS: Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy.

BACKGROUND: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. OBJECTIVES: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs). METHODS: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the re visited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications. RESULTS: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001). CONCLUSIONS: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs.

Resurfacing with Ablation of Periorbital Skin Technique: Indications, Efficacy, Safety, and 3D Assessment from a Pilot Study.

OBJECTIVES AND BACKGROUND: Nowadays, several approaches for skin rejuvenation of the lower eyelid are available. We present a new technique of resurfacing with ablation of periorbital skin (RAP) performed in a single session. METHODS: This is a retrospective study involving 20 patients showing skin elastosis with or without evidence of the nasojugal fold and atrophic and dyschromic skin or needing a combined approach of transconjuntival lower blepharoplasty for fat bag removal. RAP technique is assessed in terms of efficacy, safety, and 3D evaluation of results at 6 months' follow-up. RESULTS: Global Assessment Improvement Scale results highlighted an improvement in all cases, for both physicians (blinded to treatment) and individual subjects. Only minor adverse events (edema, erythema, and discoloration) were reported in almost all patients, lasting 2-3 weeks after treatment, and were resolved without intervention. A 3D imaging tool revealed the reduction of medium protrusions and depressions and an improved texture at 2 months. Skin recovery was inversely correlated with hemoglobin reduction. CONCLUSIONS: RAP seems to offer expert dermatologists a safe and clinically effective technique for skin rejuvenation of lower eyelids, without significant adverse events. Further studies will be performed to confirm our results.

The vascular morphology of melanoma is related to Breslow index: An in vivo study with dynamic optical coherence tomography.

BACKGROUND: Malignant melanoma is an aggressive skin cancer, which can lead to metastasis development. Vascularization enhancement is fundamental for tumor growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT) enables the in vivo evaluation of vascular patterns in skin lesions. OBJECTIVE: In vivo evaluation of the melanoma vessel morphology by means of D-OCT and correlation with Breslow index. METHODS: Retrospective analysis of histologically proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500 µm), was performed. Vessels were classified according to morphology (dots, blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and the presence/type of branches. The data were correlated with Breslow thickness. RESULTS: A total of 127 melanomas were evaluated. Dotted vessels were recorded at all depths, and their irregular distribution was associated with lesions thicker than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 µm (P = 0.031), and from 33% to 57% vs 18% at 300 µm (P = 0.021). Serpiginous and branching vessels with bulges were predominantly seen in melanomas thicker than 2 mm at 150 µm (from 14% to 27%, P < 0.001) and 300 µm of depth (from 36% to 54%, P < 0.001). LIMITATIONS: Background noise hampered vessel detection at 500 µm. No correlation with dermoscopy/histology. CONCLUSION: Vascular pattern evaluation at 150 and 300 µm provided data on tumor microvascular asset and its pattern of progression in accordance with Breslow thickness. Since vascular progression is theoretically linked with tumor aggressiveness, the study of vascular pattern related with melanoma metastatization capability is warranted.

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 differentiation of common basal cell carcinoma subtypes by microvascular and structural imaging using dynamic optical coherence tomography.

The subtype of basal cell carcinoma (BCC) influences the choice of treatment. Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent development of an angiographic version of OCT has extended the application of OCT to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This study explores D-OCT's ability to differentiate the common BCC subtypes by microvascular and structural imaging. Eighty-one patients with 98 BCC lesions, consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC) and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology centres. Blinded evaluations of microvascular and structural features were performed, followed by extensive statistical analysis of risk ratio (RR) and multiple correspondence analysis. nBCC lesions displayed most characteristic structural and vascular features. Serpiginous vessels, branching vessels, vessels creating a circumscribed figure and sharply demarcated hyporeflective ovoid structures in the dermis were all associated with a higher risk of the subtype being nBCC. The presence of highly present lines and dark peripheral borders at the margin of ovoid structures was negatively associated with iBCC. Lastly, the finding of hyporeflective ovoid structures protruding from epidermis correlated with sBCC. We identified various microvascular and structural D-OCT features that may aid non-invasive identification of BCC subtypes. This would allow clinicians to individualize and optimize BCC treatment as well as aid follow-up of non-surgical treatment.

Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2%-3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12 ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant ( PWex < 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12 ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis.

Imaging Blood Vessel Morphology in Skin: Dynamic Optical Coherence Tomography as a Novel Potential Diagnostic Tool in Dermatology.

Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel morphology and distribution. The potential of D-OCT as a diagnostic tool in dermatology is examined and may give rise to future studies on D-OCT, which are needed to confirm the aforementioned features.