Exposome and basal cell carcinoma: a multicenter case-control study.

BACKGROUND: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population. METHODS: BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study. RESULTS: The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05). CONCLUSIONS: The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk.

Non-invasive Skin Imaging in Cutaneous Lymphomas.

The diagnosis of cutaneous lymphomas is challenging and requires skin tissue for histology and immunophenotyping using immunohistochemistry and molecular studies. In recent years, the role of non-invasive imaging techniques has been described as part of the clinical assessment of cutaneous lymphoma lesions. Imaging modalities such as dermoscopy, reflectance confocal microscopy (RCM), and high frequency ultrasound (HFUS) have been shown to be very valuable in raising the clinical suspicion for lymphomas of the skin, and in distinguishing cutaneous lymphomas from inflammatory dermatoses such as lupus, psoriasis, or eczema. These non-invasive methods can be used to direct the clinician to the optimal biopsy site to maximize the histopathological results and minimize false negatives. These methods also have a potential place in monitoring treatment response. In this review we present a concise summary of the dermoscopic imaging, RCM, and HFUS features seen in cutaneous T-cell lymphomas (CTCL) and B-cell lymphomas (CBCL).

The Influence of the Exposome in the Cutaneous Squamous Cell Carcinoma, a Multicenter Case-Control Study.

INTRODUCTION: The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence. OBJECTIVES: To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort. MATERIALS AND METHOD: A multicenter case-control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer. RESULTS: A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%, p < 0.001), less recreational exposure (sunbathing, p = 0.05, and outdoor sports, p = 0.01), and a lower annual income (p = 0.01), with an increase in tobacco exposure (p < 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use (p < 0.001) and practiced more relaxation activities (p = 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC (p < 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis (p < 0.05). CONCLUSIONS: The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.

Disseminated Monomorphic Pink Papules.

A woman in her 60s with previous breast carcinoma, currently in remission, presented with pruritic lesions on her chest, arms, and back. What is your diagnosis?

Melanoma-specific survival is worse in the elderly: a multicentric cohort study.

We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P  < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P  < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P  < 0.001), as were nodular melanoma and acral lentiginous melanoma ( P  < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan-Meier survival curves showed longer melanoma-specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P  = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.

A multicenter case-control study comparing sun exposure habits and use of photoprotection measures in patients diagnosed with different types of skin cancer.

BACKGROUND: While skin cancer awareness programs have significantly furthered public understanding about the harmful effects of the sun, there is a disparity between photoprotection knowledge and protection practices. OBJECTIVE: To compare sun exposure habits and photoprotection measures in patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma versus controls. METHODS: Multicentre case-control observational study carried out by 13 Spanish dermatologists between April 2020 and August 2022. Patients diagnosed with BCC, SCC, or melanoma were considered cases. The control group consisted of individuals with no history of skin cancer. RESULTS: Of the 254 cases (56.2% female; mean age, 62.67 ± 15.65), 119 (31.2%) had BCC, 62 (16.27%) SCC, and 73 (19.1%) melanoma. The control group consisted of 127 (33.33%) individuals. Avoiding sun exposure between 12:00 and 16:00 was the most commonly used photoprotection measure (habitually/always: 63.1%), followed by the use of sunscreen (habitually/always: 58.9%). Patients with melanoma were less likely to use clothing and shade to avoid sun exposure (p < .05), whereas those with BCC and SCC reported greater use of head coverings (p = .01). BCC and SCC groups reported greater sun exposure 15 years prior, whereas controls reported greater use of sunscreen. However, at the time of this study all groups reported using SPF ≥ 21, and the majority SPF > 50. No differences were observed in photoprotection measures between people with and without a previous history of skin cancer. CONCLUSIONS: We describe differences in photoprotection measures and sun exposure patterns among patients diagnosed with different skin tumor types. Whether these differences may influence the type of tumor each developed will require further investigation.

Exploring the potential of artificial intelligence in improving skin lesion diagnosis in primary care.

Dermatological conditions are a relevant health problem. Machine learning (ML) models are increasingly being applied to dermatology as a diagnostic decision support tool using image analysis, especially for skin cancer detection and disease classification. The objective of this study was to perform a prospective validation of an image analysis ML model, which is capable of screening 44 skin diseases, comparing its diagnostic accuracy with that of General Practitioners (GPs) and teledermatology (TD) dermatologists in a real-life setting. Prospective, diagnostic accuracy study including 100 consecutive patients with a skin problem who visited a participating GP in central Catalonia, Spain, between June 2021 and October 2021. The skin issue was first assessed by the GPs. Then an anonymised skin disease picture was taken and uploaded to the ML application, which returned a list with the Top-5 possible diagnosis in order of probability. The same image was then sent to a dermatologist via TD for diagnosis, as per clinical practice. The GPs Top-3, ML model's Top-5 and dermatologist's Top-3 assessments were compared to calculate the accuracy, sensitivity, specificity and diagnostic accuracy of the ML models. The overall Top-1 accuracy of the ML model (39%) was lower than that of GPs (64%) and dermatologists (72%). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained (n = 82), the balanced Top-1 accuracy of the ML model increased (48%) and in the Top-3 (75%) was comparable to the GPs Top-3 accuracy (76%). The Top-5 accuracy of the ML model (89%) was comparable to the dermatologist Top-3 accuracy (90%). For the different diseases, the sensitivity of the model (Top-3 87% and Top-5 96%) is higher than that of the clinicians (Top-3 GPs 76% and Top-3 dermatologists 84%) only in the benign tumour pathology group, being on the other hand the most prevalent category (n = 53). About the satisfaction of professionals, 92% of the GPs considered it as a useful diagnostic support tool (DST) for the differential diagnosis and in 60% of the cases as an aid in the final diagnosis of the skin lesion. The overall diagnostic accuracy of the model in this study, under real-life conditions, is lower than that of both GPs and dermatologists. This result aligns with the findings of few existing prospective studies conducted under real-life conditions. The outcomes emphasize the significance of involving clinicians in the training of the model and the capability of ML models to assist GPs, particularly in differential diagnosis. Nevertheless, external testing in real-life conditions is crucial for data validation and regulation of these AI diagnostic models before they can be used in primary care.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Challenges for New Adopters in Pre-Surgical Margin Assessment by Handheld Reflectance Confocal Microscope of Basal Cell Carcinoma; A Prospective Single-center Study.

Introduction: In vivo reflectance confocal microscopy (RCM) is a useful tool for assessing pre-surgical skin tumor margins when performed by a skilled, experienced user. The technique, however, poses significant challenges to novice users, particularly when a handheld RCM (HRCM) device is used. Objectives: To evaluate the performance of an HRCM device operated by a novice user to delineate basal cell carcinoma (BCC) margins before Mohs micrographic surgery (MMS). Methods: Prospective study of 17 consecutive patients with a BCC in a high-risk facial area (the H zone) in whom tumor margins were assessed by HRCM and dermoscopy before MMS. Predicted surgical defect areas (cm2) were calculated using standardized photographic digital documentation and compared to final defect areas after staged excision. Results: No significant differences were observed between median HRCM-predicted and observed surgical defect areas (2.95 cm2 [range: 0.83-17.52] versus 2.52 cm2 [range 0.71-14.42]; P = 0.586). Dermoscopy, by contrast, produced significantly underestimated values (median area of 1.34 cm2 [0.41-4.64] versus 2.52 cm2 [range 0.71-14.42]; P < 0.001). Confounders leading to poor agreement between predicted and observed areas were previous treatment (N = 5), a purely infiltrative subtype (N = 1), and abundant sebaceous hyperplasia (N = 1). Conclusions: Even in the hands of a novice user, HRCM is more accurate than dermoscopy for delineating lateral BCCs margins in high-risk areas and performs well at predicting final surgical defects.

Using Artificial Intelligence as a Diagnostic Decision Support Tool in Skin Disease: Protocol for an Observational Prospective Cohort Study.

BACKGROUND: Dermatological conditions are a relevant health problem. Each person has an average of 1.6 skin diseases per year, and consultations for skin pathology represent 20% of the total annual visits to primary care and around 35% are referred to a dermatology specialist. Machine learning (ML) models can be a good tool to help primary care professionals, as it can analyze and optimize complex sets of data. In addition, ML models are increasingly being applied to dermatology as a diagnostic decision support tool using image analysis, especially for skin cancer detection and classification. OBJECTIVE: This study aims to perform a prospective validation of an image analysis ML model as a diagnostic decision support tool for the diagnosis of dermatological conditions. METHODS: In this prospective study, 100 consecutive patients who visit a participant general practitioner (GP) with a skin problem in central Catalonia were recruited. Data collection was planned to last 7 months. Anonymized pictures of skin diseases were taken and introduced to the ML model interface (capable of screening for 44 different skin diseases), which returned the top 5 diagnoses by probability. The same image was also sent as a teledermatology consultation following the current stablished workflow. The GP, ML model, and dermatologist's assessments will be compared to calculate the precision, sensitivity, specificity, and accuracy of the ML model. The results will be represented globally and individually for each skin disease class using a confusion matrix and one-versus-all methodology. The time taken to make the diagnosis will also be taken into consideration. RESULTS: Patient recruitment began in June 2021 and lasted for 5 months. Currently, all patients have been recruited and the images have been shown to the GPs and dermatologists. The analysis of the results has already started. CONCLUSIONS: This study will provide information about ML models' effectiveness and limitations. External testing is essential for regulating these diagnostic systems to deploy ML models in a primary care practice setting.

Matching-adjusted indirect comparison of efficacy outcomes in trials of calcipotriol plus betamethasone dipropionate foam and cream formulations for the treatment of plaque psoriasis.

BACKGROUND AND OBJECTIVES: Once-daily, fixed-combination calcipotriol 50 µg/g (Cal) plus betamethasone dipropionate 0.5 mg/g (BD) is available in aerosol foam and cream formulations. As no head-to-head data are available, we use a matching-adjusted indirect comparison (MAIC) approach to compare Cal/BD foam and cream. METHODS: Anchored and unanchored MAIC analyses were conducted using individual patient data (IPD) from five Cal/BD foam trials and two trials of Cal/BD cream. Outcomes of interest were the proportion of patients with Physician's Global Assessment (PGA) success and the mean reduction in modified Psoriasis Area and Severity Index (mPASI). RESULTS: In the anchored MAIC, patients were more likely to achieve PGA success after 4 weeks of Cal/BD foam than after 8 weeks of Cal/BD cream and had larger mean improvements in mPASI (p < .01 in EU mPASI analysis). In unanchored analyses, 4 weeks of Cal/BD foam treatment was statistically significantly more efficacious in inducing PGA success than 8 weeks of Cal/BD cream (p < .01 in five of six comparisons). Mean reductions in mPASI were consistently statistically significantly greater with Cal/BD foam than with Cal/BD cream. CONCLUSIONS: Use of Cal/BD foam consistently shows significantly greater improvements in PGA and mPASI outcomes, compared with Cal/BD cream.

Spitzoid proliferative nodules arising in a congenital melanocytic naevus: A case report with clinical, dermoscopic and histologic correlation.

Proliferative nodules (PNs) are benign nodular proliferation of melanocytes occurring within congenital melanocytic naevi (CMN). Differential diagnosis between PN and melanoma is challenging for clinicians and pathologists. We describe the case of a 9-month-old boy who developed multiple nodules arising in a medium-sized CMN. Clinically, pink papules were observed, with dotted vessels on dermoscopy, suggesting spitzoid PN. On histopathological examination, the dermoscopic findings correlated with the vertical vessels of a spitzoid PN. Dermoscopy could be a useful tool to differentiate PN from melanoma. However, further studies describing the dermoscopic features of the different PN subtypes are needed. Histopathology remains the gold standard for definitive diagnosis aided by ancillary molecular tests such as fluorescence in situ hybridization or comparative genomic hybridization.

Lentigo Maligna: Clinical Presentation and Appropriate Management.

Lentigo maligna (LM) is a type of melanoma in situ that has distinctive characteristics regarding epidemiology, risk factors and clinical features. In addition, LM has a potential to progress to an invasive tumor with potentially aggressive behavior: lentigo maligna melanoma (LMM). Overall, LM has a very good prognosis, whereas LMM has the same prognosis as other invasive melanomas with similar Breslow thickness. LM/LMM represents a challenging entity not only regarding the diagnosis but also regarding the management. Diagnostic criteria are not well established, and there is an overlap of clinical, dermoscopic and pathological features with other benign pigmented skin lesions such as lentigines, pigmented actinic keratoses or macular seborrheic keratoses. LM/LMM's common appearance within photodamaged skin makes lesion border identification difficult. Wide excisions are often required, but since LM/LMM typically appears on cosmetically sensitive areas such as the face, sometimes large excisions are not possible nor desirable. In this sense, specialized approaches have been developed such as margin-controlled surgery or image-guided treatment using reflectance confocal microscopy. Other treatments for LM such as cryosurgery, imiquimod, radiotherapy or photodynamic therapy have been proposed, although recurrence/persistence is common. The current manuscript reviews extensively the published data regarding the diagnosis, treatment and management of both complex entities LM and LMM.