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Introduction: Being able to recognize high-risk facial basal cell carcinoma (BCC) may lead to fewer incomplete excisions and inappropriate treatments. Objectives: We sought to investigate clinical and dermoscopic criteria for predicting facial BCC subtypes, analyze the interobserver agreement between readers, and develop a diagnostic algorithm to predict high-risk histopathological subtype. Methods: In this single-center, retrospective investigation, 6 independent readers evaluated predefined clinical and dermoscopic criteria in images of histopathologically verified primary facial BCCs including: topography, border demarcation, vessels, ulceration, white porcelain areas, shiny white blotches and strands, and pigmented structures and vessels within ulceration. Results: Overall, 297 clinical and dermoscopic image pairs were analyzed. The strongest associations with high-risk subtype were: “bumpy” topography (OR 3.8, 95% CI, 3.1-4.7), ill-defined borders (OR 3.4, 95% CI 3.1-4.7), white porcelain area (OR 3.5, 95% CI 2.8-4.5), and vessels within ulceration (OR 3.1, 95% CI 2.4-4.1). Predominantly focused vessels were a positive diagnostic criterium for either nodular (OR 1.7, 95% CI 1.3-2.2) or high-risk (OR 2.0, 95% CI 1.6-2.5) subtypes and a strong negative diagnostic criterium for superficial BCC (OR 14.0, 95% CI 9.6-20.8). Interobserver agreement ranged from fair to substantial (κ=0.36 to 0.72). A diagnostic algorithm based on these findings demonstrated a sensitivity of 81.4% (95% CI, 78.9-83.7%) and a specificity of 53.3% (95% CI, 49.7-56.9%) for predicting high-risk BCC subtype. Conclusions: Integration of both clinical and dermoscopic features (including novel features such as topography and vessels within ulceration) are essential to improve subtype prediction of facial BCCs and management decisions.

Standard assessment of immune infiltration of biopsies is not sufficient to accurately predict response to immunotherapy. Here, the authors show that reflectance confocal microscopy can be used to quantify dynamic vasculature and inflammatory features to better predict treatment response in skin cancers.

Introduction: A wide range of descriptive terms have been used for dermoscopic findings in intraepidermal carcinoma (IEC) and the clinical diagnostic accuracy of IEC can be challenging. Furthermore, dermoscopic findings in IEC have only rarely been evaluated in fair-skinned populations. Objectives: To measure the interobserver agreement between dermatologists for dermoscopic findings in IEC. Furthermore, to describe the frequency of these findings in a predominantly fair-skinned population. Methods: One hundred dermoscopic images of histopathologically verified IECs were collected. The 11 most common dermoscopic findings described in previous studies were re-defined in a new terminology in a pre-study consensus meeting. Images were assessed by eight experienced international dermoscopists. The frequency of findings and the interobserver agreement was analyzed. Results: Scales (83%), dotted/glomerular vessels (77%), pinkish-white areas (73%) and hemorrhage (46%) were the most commonly present dermoscopic findings. Pigmented structures were found in 32% and shiny white structures (follicular or stromal) in 54% of the IEC. Vascular structures (vessels and/or hemorrhage) could be seen in 89% of the lesions. Overall, the interobserver agreement for the respective dermoscopic findings was poor to moderate, with the highest kappa values noted for scales (0.55) and hemorrhage (0.54) and the lowest for pinkish-white areas (0.015). Conclusion: Our results confirm those of previous studies on dermoscopy in IEC, including the frequency of pigmented structures despite the fair-skinned population. The interobserver agreement was relatively low. The proposed new terminology and our findings can hopefully serve as a guideline for researchers, teachers and students on how to identify IEC.

Abstract Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1–2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1–2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.

Introduction: Among the various widely recognized basal cell carcinoma (BCC) clinical patterns, linear basal cell carcinoma (LBCC) is an uncommon morphologic variant of BCC. Objective: Describe the clinical and dermoscopic characteristics of LBCC. Methods: Retrospective study including LBCC cases from 5 dermatology centers in North and South America. Biopsy-proven primary BCCs, that presented with at least 3:1 length:width ratio on physical examination, irrespective of tumor subtype or location, were included. Clinical and dermoscopic analysis were performed by 2 experts in dermoscopy. Results: Eighteen cases of LBCC met our inclusion criteria and were included in the study. Median age at diagnosis was 86.0 years, 10 patients (58.8%) were males. Regarding anatomic location, 11/18 (61.1%) were located on the head and neck, 5/18 (27.7%) cases were found on the trunk, and 2 on lower extremities (11.1%). Under dermoscopy, 15/18 (83.3%) of LBCC were pigmented. All tumors displayed at least one of the BCC-specific dermoscopic criteria the most common being blue-grey globules (72.2%). Conclusions: Dermoscopy might be useful in the differentiation of LBCC from other diagnoses presenting as linear lesions such as scars, scratches/erosions, and tattoos, among others. Some of these lesions might be confused by naked eye examination alone.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Tertiary lymphoid structures (TLS) are specialized lymphoid formations that serve as local repertoire of T- and B-cells at sites of chronic inflammation, autoimmunity, and cancer. While presence of TLS has been associated with improved response to immune checkpoint blockade therapies and overall outcomes in several cancers, its prognostic value in basal cell carcinoma (BCC) has not been investigated. Herein, we determined the prognostic impact of TLS by relating its prevalence and maturation with outcome measures of anti-tumor immunity, namely tumor infiltrating lymphocytes (TILs) and tumor killing. In 30 distinct BCCs, we show the presence of TLS was significantly enriched in tumors harboring a nodular component and more mature primary TLS was associated with TIL counts. Moreover, assessment of the fibrillary matrix surrounding tumors showed discrete morphologies significantly associated with higher TIL counts, critically accounting for heterogeneity in TIL count distribution within TLS maturation stages. Specifically, increased length of fibers and lacunarity of the matrix with concomitant reduction in density and alignment of fibers were present surrounding tumors displaying high TIL counts. Given the interest in inducing TLS formation as a therapeutic intervention as well as its documented prognostic value, elucidating potential impediments to the ability of TLS in driving anti-tumor immunity within the tumor microenvironment warrants further investigation. These results begin to address and highlight the need to integrate stromal features which may present a hindrance to TLS formation and/or effective function as a mediator of immunotherapy response.

Background: Minimal knowledge exists regarding skin cancers in Black individuals, which may adversely affect patient care. Objectives: To describe clinical features and risk factors of skin cancers in Black individuals. Methods: Retrospective study of Black individuals diagnosed with skin cancer between January 2000 and January 2020 at our institution. Results: 38,589 patients were diagnosed with skin cancer, of which 165 were Black. One-hundred-thirteen of these Black individuals were diagnosed with melanoma, 35 with squamous cell carcinoma (SCC), and 17 with basal cell carcinoma (BCC). Most melanomas (80.0%, n=90) were of the acral subtype; 75% (6 of 8 cases with dermoscopic images) displayed a parallel ridge pattern (PRP). The surrounding uninvolved background skin was visible in 7 cases, all demonstrating a PRP. This disappeared adjacent to most of the melanoma lesions (n=4, 57.1%) – creating a peripheral hypopigmented “halo”. The nonmelanoma skin cancers were pigmented and had similar dermoscopic features as reported in predominantly white populations. Most SCCs (n=5, 71.4%) had a hypopigmented “halo” and most BCCs (n=10, 55.6%) had an accentuated reticular network adjacent to the lesions. Most (80.0%, n=28) SCC patients had a chronic inflammatory condition. Two BCC patients (16.7%) had Gorlin syndrome. Conclusions: Skin cancers are pigmented in Black individuals. In both ALMs and SCCs, we noted a peripheral rim of hypopigmentation between the lesions and the surrounding uninvolved background skin, while BCCs had accentuation of the background pigmentation adjacent to the lesions. Most acral melanomas displayed a PRP, which was also seen in surrounding uninvolved background skin.

Importance: Dermoscopic triage algorithms have been shown to improve beginners' abilities for identifying pigmented skin lesions requiring biopsy. Objective: To estimate the diagnostic accuracy of the Triage Amalgamated Dermoscopic Algorithm (TADA) for pigmented and nonpigmented skin cancers. Secondarily, to compare TADAs performance to those of existing triage algorithms for the identification of pigmented skin cancers. Design: Cross-sectional, observational, reader study that took place at a beginner and intermediate level dermoscopy course. Participants: Two hundred medical professionals of various specialties attended the course and 120 voluntarily joined the study (60% participation rate). Exposures: After receiving basic dermoscopy training, participants evaluated 50 polarized, dermoscopic images of pigmented (22 benign, 18 malignant) and nonpigmented (1 benign, 9 malignant) skin lesions using TADA. Pigmented lesions were also evaluated using the Three-Point Checklist and AC Rule. With TADA, participants first determined if a lesion was an unequivocal angioma, dermatofibroma, or seborrheic keratosis, which would exclude it from further evaluation. All other lesions were assessed for architectural disorder, starburst pattern, blue-black or gray color, shiny white structures, negative network, ulcer/erosion, or vessels. Any one feature indicated suspicion for malignancy. Results: Most participants were dermatologists (n=64, 53.3%) or primary care physicians (n=41, 34.2%), and many lacked previous dermoscopy training (n=52, 43.3%). TADA's sensitivity and specificity for all skin cancers was 94.6% (95% CI=93.4-95.7%) and 72.5% (95% CI=70.1-74.7%), respectively. For pigmented skin cancers, the sensitivity and specificity were 94.0% (95% CI=92.9-95.0%) and 75.5% (95% CI=73.8-77.2%). This compared to 71.9% (95%CI=69.8-73.9%) and 81.4% (95%CI=79.7-83.0%) for the Three- Point Checklist and 88.6% (95%CI=87.1-89.9%) and 78.7% (95%CI=76.9-80.3%) for the AC Rule. Conclusions: These results suggest that TADA compares favorably to existing triage algorithms and might be a useful triage tool with high sensitivity and specificity for pigmented and nonpigmented skin cancers. Further studies are needed to validate these preliminary observations.

Clinical observations and an expanding knowledge of cell-to-cell communication have led us to speculate that the finding of a melanocytic nevus in conjunction with a seborrheic keratosis is more than a coincidental collision of two lesions. Here we present five cases demonstrating dermoscopic features of both melanocytic lesions and seborrheic keratoses with corresponding histology. Four cases demonstrate dermoscopic features of a melanocytic nevus and seborrheic keratosis, and the final case a melanoma arising in association with a seborrheic keratosis.