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Background: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. Objective: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. Methods: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. Results: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. Limitations: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. Discussion: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

Summary Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. Results In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01–0·76] and vitiligo (OR 0·07, 95% CI 0·006–0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02–0·31), lichenoid reactions (OR 0·15, 95% CI 0·03–0·77) and eczematous reactions (OR 0·24, 95% CI 0·07–0·78), all compared with pruritic rash. Conclusions Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy.Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer.The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus.Clinical awareness and specialized dermatological consultation should be advocated.

The World Health Organization declared the global monkeypox outbreak a public health emergency of international concern in July 2022. In response, the American Academy of Dermatology and International League of Dermatological Societies expanded the existing COVID-19 Dermatology Registry to become the "AAD/ILDS Dermatology COVID-19, Monkeypox, and Emerging Infections Registry." The goal of the registry is to rapidly collate cases of monkeypox and other emerging infections and enable prompt dissemination of findings to front-line healthcare workers and other members of the medical community. The registry is now accepting reports of monkeypox cases and cutaneous reactions to monkeypox/smallpox vaccines. The success of this collaborative effort will depend on active case entry by the global dermatology community.

We present an interesting case of a patient with post-kala-azar dermal leishmaniasis (PKDL), encountered in Greece. The man developed PKDL while on treatment with lenalidomide and corticosteroids for multiple myeloma. PKDL is an important neglected tropical disease. It usually occurs in the Indian subcontinent and East Africa. To our knowledge, this is the first case of PKDL in a European territory. The case should raise awareness among clinicians that PKDL could be encountered in European countries, and further strengthens the immunosuppression hypothesis for the causation of PKDL.

Several studies have started investigating the safety of temporal rejuvenation using soft tissue fillers. However, as the temporal region is highly vascularized, adverse events due to intravascular injection are of primary concern. The scarcity of treatment guidelines to date have focused primarily on avoiding the superficial and middle temporal arteries. The aim of the present anatomical study was to describe the topography of the deep temporal arteries (DTAs) with reference to superficial landmarks, to aid clinicians who perform temporal injections.The tissue layers of eight fresh-frozen cephalic cadavers were dissected and assessed, bilaterally in the temporal region (N = 16). Distance (D) of the anterior (D1 and D3) and posterior (D2 and D4) arteries was measured from (i) the zygomaticofrontal suture line at the lateral orbital rim (D1 and D2) and (ii) the junction of the superior border of the zygomatic arch and lateral orbital rim (D3 and D4). The distance between the anterior and posterior DTAs was also recorded, at the two regions (D5).Bifurcations of the DTAs were observed in 18.75% (3/16) and 12.5% (2/16) of cases, for the anterior and posterior branches, respectively. On average [mean (standard deviation)], D1 (anterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 1.56 cm (0.59); D2 (posterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 2.98 cm (0.70); D3 (anterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 1.14 cm (0.63); D4 (posterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 2.37 cm (0.62); and D5 (distance between the anterior and posterior DTAs) = 1.54 cm (0.68).To help avoid vascular adverse events while performing temporal injections, aesthetic clinicians should be conscientious of safety implications related to the anatomical location of the DTAs and their ramifications.

New onset or exacerbation of pre-existing psoriasis after therapeutic TNF-α inhibition is a well-described phenomenon. Over the last two decades, similar cases of paradoxical psoriasis have been reported following the administration of other biologic agents. We aimed to review all published cases of induced or exacerbated psoriasis after biologic therapy other than anti-TNF-α agents in order to further elucidate the pathophysiology of this phenomenon. A systematic literature review in the Medline database regarding any relevant case series or case reports on new onset or exacerbation of psoriasis after the administration of biologic agents targeting B cells, T cell co-stimulation, interleukin-1, interleukin-6, interleukin-17 and interleukin-12/23 was performed using appropriate key words. The literature search revealed nine articles (nine cases) of paradoxical psoriasis after ustekinumab and eight articles (nine cases) after secukinumab administration, both of which are approved therapies for psoriasis Moreover, 15 articles (23 cases) for rituximab, nine articles (12 cases) for abatacept, eight articles (nine cases) for tocilizumab, and one case report for anakinra have been published. In the majority of cases, patients had no prior history of psoriasis while 18 patients presented with exacerbation of pre-existing psoriatic lesions. Paradoxical psoriasis is not a specific adverse event of TNF-α inhibitors but is a possible side effect of any biologic agent interfering with the immune system. Awareness among physicians regarding early recognition is mandatory. Further clinical and experimental data are needed in order to unravel the pathophysiology of this unexpected phenomenon.

Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the “one-size-fits-all” approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with AD into distinct endotypes and clinical phenotypes based on biomarkers that will contribute to the development of precision medicine in AD. The development of reliable biomarkers that may distinguish which patients with AD are most likely to benefit from specific targeted therapies is a complex procedure and to date none of the identified candidate biomarkers for AD has been validated for use in routine clinical practice. Reliable biomarkers in AD are expected to improve diagnosis, evaluate disease severity, predict the course of disease, the development of comorbidities, or the therapeutic response, resulting in effective and personalized treatment of AD. Among the studied AD potential biomarkers, thymus and activation-regulated chemokine/C-C motif ligand 17 (TARC/CCL17) has the greatest evidence-based support for becoming a reliable biomarker in AD correlated with disease severity in both children and adults. In this review, we present the most prominent candidate biomarkers in AD and their suggested use.

High-risk cSCC is defined as invasive cSCC staged as N0 (without detectable regional lymph nodes) and M0 (without distant metastasis), that has features associated with a higher risk of poorer prognosis. The focus of this review is on the recent advances in the diagnosis and management of high-risk cSCC. The interest in high-risk cSCC relies on its higher risk of progression to advanced cSCC, as it represents the main pool of cSCCs that give rise to advanced tumors. Assessment of the risk is thus particularly relevant for common cSCC to identify the few with a high-risk risk of local recurrence, metastasis, or disease-specific death among all other low-risk tumors. The timely diagnosis and effective treatment of high-risk cSCCs may halt their further progression and aim to prevent and lower the incidence of advanced cSCCs. Clearance of the tumor with negative surgical margins is the main goal of surgery, which is the primary treatment of cSCC. It seems that it is difficult to discern the group of high-risk cSCCs that may benefit from adjuvant RT, as a universal beneficial effect for a cSCC with any high-risk factor which was resected with clear surgical margins has not been established. In the case of a high-risk cSCC with positive margins after surgery, and re-excision not feasible, post-operative radiotherapy is performed when possible. Recommendations on further management are discussed. Regarding the follow-up of patients diagnosed with high-risk cSCC, factors to consider regarding the frequency and intensity of the follow-up schedule include the risk and possible time of occurrence of metastasis from cSCC.

Background In the era of precision medicine, identification of possible predictive factors of clinical response to treatment is fundamental. This need is particularly strong for anogenital warts (AGW), because there are several treatment modalities with different clearance and recurrence rates. However, data regarding the effect of mental health parameters on response to treatment in patients with AGW are lacking. Objectives The purpose of the present study was to evaluate the association between patients' mental health parameters and AGW treatment outcomes. Methods This was a single-centre, prospective study that included newly diagnosed male patients with AGW. At their initial visit, all patients completed the State-Trait Anxiety Inventory (STAI), the Symptom Checklist-90-Revised (SCL-90-R), and the Eysenck Personality Questionnaire (EPQ) questionnaires, which evaluate anxiety, psychopathological manifestations, and personality traits, respectively. All patients received cryotherapy until clearance of lesions and were followed up for 18 months for detection of recurrences. Results The study included 167 male patients. The mean number of days for AGW clearance was 89+/-65. During the 18-month follow up, 28 % of participants showed a recurrence, after a mean number of 150+/-132 days. No statistically significant association was detected between questionnaires scores and a) time needed for AGW clearance, b) time until 1st recurrence, and c) number of recurrences. Conclusion If confirmed, our findings indicate that we may not need to modify our AGW treatment plan according to a patient's mental health profile.

Prior skin image datasets have not addressed patient-level information obtained from multiple skin lesions from the same patient. Though artificial intelligence classification algorithms have achieved expert-level performance in controlled studies examining single images, in practice dermatologists base their judgment holistically from multiple lesions on the same patient. The 2020 SIIM-ISIC Melanoma Classification challenge dataset described herein was constructed to address this discrepancy between prior challenges and clinical practice, providing for each image in the dataset an identifier allowing lesions from the same patient to be mapped to one another. This patient-level contextual information is frequently used by clinicians to diagnose melanoma and is especially useful in ruling out false positives in patients with many atypical nevi. The dataset represents 2,056 patients (20.8% with at least one melanoma, 79.2% with zero melanomas) from three continents with an average of 16 lesions per patient, consisting of 33,126 dermoscopic images and 584 (1.8%) histopathologically confirmed melanomas compared with benign melanoma mimickers., Measurement(s) melanoma • Skin Lesion Technology Type(s) Dermoscopy • digital curation Factor Type(s) approximate age • sex • anatomic site Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.13070345

The MITF(E318K) variant confers moderate risk for cutaneous melanoma. While there are small studies suggesting that this risk is associated with other malignancies (e.g. renal cell carcinoma), little is known about the role of this variant in specifying risk for other cancers. In this study, we perform a systematic review and meta-analysis of the published data as a backdrop to a whole-exome sequence(WES)-based characterization of MITF(E318K) risk for various cancers in sporadic samples from the TCGA and several genetically-enriched patient cohorts. We found minimal evidence of MITF(E318K)’s contribution to non-melanoma cancer risk among individuals with low inherited risks of melanoma (OR 1.168; 95% CI 0.78–1.74; p = 0.454), suggesting that earlier reports of an association between this variant and other malignancies may be related to shared environmental or polygenic risk factors rather than MITF(E318K). Interestingly, an association was observed with uterine carcinosarcoma, (OR 9.24; 95% CI 2.08–37.17; p = 0.024), which was not previously described. While more research needs to be completed, this study will help update cancer screening recommendations for patients with the MITF(E318K) variant.

BACKGROUND Oxidative hair dyes are an important source of chemical exposure and a major risk factor for the development of occupational and non-occupational allergic contact dermatitis (ACD) worldwide. OBJECTIVE To identify the frequency of common allergens associated with occupational and non-occupational ACD to hair dyes during the last 10 years, in Greece. METHODS We retrospectively reviewed the medical records of patients with suspected ACD to hair dyes from 2010-2019. All patients with patch-test-confirmed ACD to hair dyes were evaluated. RESULTS Out of 501 patients with suspected ACD to hair dyes, 362 had at least one positive reaction to hair dye allergens (62.4% were customers and 37.6% were hairdressers). The mean age of customers and hairdressers was 43.8 years and 30.8 years, respectively. Of the customers, 58.9% were exposed to dyes for >10 years and 61% of hairdressers for

Background: Patients with localized cutaneous squamous cell carcinoma (cSCC) have different risk for disease-specific death (DSD) from patients with metastatic cSCC. Patients and Methods: We conducted a sensitivity meta-analysis to identify the risk factors associated with DSD, in patients with localized cSCC at initial diagnosis (without locoregional or distant metastasis). Results: Nine studies, with 5,205 patients, were included. Median follow-up ranged from 18 to 81 months. The number of deaths due to cSCC ranged from 3 to 40. Patients with immunosuppression were almost 2 times more likely to die from cSCC compared to immunocompetent patients (risk ratio: 1.85, 95% CI: 1.32–2.61). There was a positive but nonsignificant overall association with DSD for depth beyond fat, tumor diameter, presence of perineural invasion, location, and thickness. These results should be interpreted with caution, as there was limited evidence-based data on DSD in localized cSCC, due to the small number of studies reporting DSD, the absence of reporting the margin status, the variability of selected risk factors across studies, and the variability of definition of risk factors. Conclusions: In our meta-analysis, in localized cSCC at initial diagnosis, patients with immunosuppression were at significantly higher risk to die from cSCC. Our findings further highlight the need for a standardized set of risk factors to be included in studies on prognosis of cSCC and for including margin status and DSD among the studied outcomes.

Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I2 statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39–63%) with high heterogeneity at I2: 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51–77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36–75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63–78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.

BACKGROUND The human face significantly affects the individuals' quality of life, attitude, and mental state. The study of anatomy would always be on the spotlight, as the beauty of the face is desired by humans worldwide. However, age, stress, and negative emotions could lead to stimulation of the corrugator supercilii and procerus muscles in the glabellar region and, subsequently, to alterations in face's characteristics, which could be associated with isolation and avoidance of engaging in social contacts. AIMS Here, we aimed to examine the degree to which treatment with botulinum toxin type A (BoNT A) can affect patients' quality of life and mental state. PATIENTS/METHODS The data collection was performed using 11 questionnaires, which were filled by 83 individuals who underwent BoNT A treatment (sex, 95% female and 5% male; mean age, 48 years). RESULTS The results showed that the treatment with BoNT A improved the patients' social and psychological behavior, and their opinion regarding their appearance. This effect developed within 1 month following completion of the treatment. Moreover, the effect was higher in patients' social behavior and was better in patients aged 40-49 years compared to those aged

The COVID-19 pandemic has led to delays in diagnosis and treatment of patients with skin cancer: presentational delay of patients to the physician, diagnostic referral delay due to restrictions of diagnostic capacities, and/or treatment delay (decision to defer treatment due to increased risk of COVID-19 transmission or health policy restrictions to treatment capacities).

Introduction: Basal cell carcinoma (BCC) quite frequently presents as multiple tumors in individual patients. Neoplasm’s risk factors for local recurrence have a critical impact on therapeutic management. Objective: To detect risk factors for multiple BCCs (mBCC) in individual patients and to describe clinical and dermatoscopic features of low- and high-risk tumors. Materials &amp, Methods: Our study included 225 patients with 304 surgically excised primary BCCs. All patients’ medical history and demographics were recorded. Clinical and dermatoscopic images of BCCs were evaluated for predefined criteria and statistical analyses were performed. Results: Grade II-III sunburns before adulthood (OR 2.146, p = 0.031) and a personal history of BCC (OR 3.403, p &lt, 0.001) were the major predisposing factors for mBCC. Clinically obvious white color (OR 3.168, p &lt, 0.001) and dermatoscopic detection of white shiny lines (OR 2.085, p = 0.025) represented strongly prognostic variables of high-risk BCC. Similarly, extensive clinico-dermatoscopic ulceration (up to 9.2-fold) and nodular morphology (3.6-fold) raise the possibility for high-risk BCC. On the contrary, dermatoscopic evidence of blue-black coloration had a negative prognostic value for high-risk neoplasms (light OR 0.269, p &lt, 0.001/partial OR 0.198, p = 0.001). Conclusions: Profiling of mBCC patients and a thorough knowledge of high-risk tumors’ clinico-dermatoscopic morphology could provide physicians with important information towards prevention of this neoplasm.

Background Imiquimod 3.75% is a field‐directed treatment for actinic keratosis that can detect and treat clinical and subclinical lesions across an entire sun‐exposed field. The detection of subclinical lesions is evidenced by an increase in lesions to the maximum lesion count during treatment (L max). We report clinical outcomes for the first 15 patients treated with imiquimod 3.75% in daily clinical practice in Greece. Methods Fifteen patients with actinic keratosis lesions were treated with imiquimod 3.75% in an outpatient setting in two 2‐week treatment cycles separated by a 2‐week treatment‐free interval. Actinic keratosis lesions were counted before treatment, at the end of the first treatment cycle (Week 2; L max), and 2 weeks after the second treatment cycle (Week 8). Local skin reactions (LSR) were also evaluated at Weeks 2 and 8. Results The median baseline actinic keratosis lesion count was 25, which increased to a median L max of 29 at Week 2 and decreased to a median of 5 at Week 8. The median percentage and absolute reduction in actinic keratosis lesions from L max to Week 8 were 87% and 23%, respectively. Most of the LSR were mild‐to‐moderate in intensity at Week 2 and had resolved by Week 8. Conclusion Imiquimod 3.75% effectively detected and cleared both the clinical and subclinical actinic keratosis lesions across the entire sun‐exposed field in this cohort of Greek patients. Treatment was well tolerated.

Along with traditional effects of aging and carcinogen exposure—inherited DNA variation has substantial contribution to cancer risk. Extraordinary progress made in analysis of common variation with GWAS methodology does not provide sufficient resolution to understand rare variation. To fulfill missing classification for rare germline variation we assembled dataset of whole exome sequences from>2000 patients (selected cases tested negative for candidate genes and unselected cases) with different types of cancers (breast cancer, colon cancer, and cutaneous and ocular melanomas) matched to more than 7000 non-cancer controls and analyzed germline variation in known cancer predisposing genes to identify common properties of disease-associated DNA variation and aid the future searches for new cancer susceptibility genes. Cancer predisposing genes were divided into non-overlapping classes according to the mode of inheritance of the related cancer syndrome or known tumor suppressor activity. Out of all classes only genes linked to dominant syndromes presented significant rare germline variants enrichment in cases. Separate analysis of protein-truncating and missense variation in this list of genes confirmed significant prevalence of protein-truncating variants in cases only in loss-of-function tolerant genes (pLI 0.9). In addition to findings in genetically enriched cases, we observed significant burden of rare variation in unselected cases, suggesting substantial role of inherited variation even in relatively late cancer manifestation. Taken together, our findings provide reference for distribution and types of DNA variation underlying inherited predisposition to some common cancer types.

We present an interesting and unusual case of a 5 cm well-demarcated erosive plaque on the labia minora, extending to the vagina in an 85-year-old woman, causing pain and discomfort for 2 years. The patient was treated several times with topical and systemic anti-fungals without benefit. Histopathology revealed a typical superficial spreading basal cell carcinoma (BCC) and the patient was referred to a gynecologist for surgical excision. Our case is an alert of BCCs arising on the genital area because they are rare and patients usually present with large lesions, as they do not seek medical attention for what they consider simple irritation. Physicians easily misdiagnose these cancers as inflammatory or infectious dermatoses.

Background: Cemiplimab is the first treatment approved in the US (as cemiplimab-rwlc) for patients with metastatic basal cell carcinoma (mBCC) or locally advanced disease (laBCC) after hedgehog inhibitor (HHI) treatment or for whom an HHI is not appropriate. Cemiplimab provided substantial clinical benefit and an acceptable safety profile in patients with laBCC who discontinued HHI therapy due to progressive disease (PD), intolerance, or no better than stable disease (SD) after 9 months (NCT03132636). Here, we present the primary analysis of the mBCC cohort. Methods: Patients with mBCC (nodal or distant) post-HHI treatment received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until PD. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Key secondary endpoints included safety and tolerability, ORR per investigator (INV) assessment, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and complete response (CR) rate (data cutoff date: May 20, 2021). Results: Fifty-four patients were enrolled (70.4% male; median age 63.5 years [range, 38−90]; Eastern Cooperative Oncology Group performance status 0 [66.7%] and 1 [33.3%]). Median duration of follow-up was 8.4 months (range 1.5-36.2). ORR per ICR was 24.1% (95% confidence interval [CI], 13.5-37.6); with 1 CR and 12 partial responses (PRs). ORR per INV was 25.9% (95% CI, 15.0-39.7), with 2 CRs and 12 PRs. Among responders, median time to response per ICR was 4.0 months (range, 2.0−10.5). Estimated median DOR per ICR was 16.7 months (95% CI, 9.8-not evaluable). Disease control rate was 63.0% (95% CI, 48.7-75.7) per ICR and 70.4% (95% CI, 56.4-82.0) per INV. Median OS was not reached. Median PFS per ICR was 8.3 months (95% CI, 4.2-15.9). The most common treatment-related adverse events were fatigue (37.0%), diarrhea (14.8%), pruritus (13.0%), hyperthyroidism (9.3%), and arthralgia (9.3%) as well as hypothyroidism, asthenia, constipation, and maculo-papular rash (7.4% each). There were no treatment-related deaths. Conclusions: Cemiplimab provided clinically meaningful antitumor activity, including durable responses, and an acceptable safety profile in patients with mBCC who had progressed on or were intolerant to HHI therapy. Citation Format: Karl Lewis, Ketty Peris, Aleksander Sekulic, Alexander J. Stratigos, Lara Dunn, Zeynep Eroglu, Anne Lynn S. Chang, Michael R. Migden, Suk-Young Yoo, Kosalai Mohan, Ebony Coates, Emmanuel Okoye, Timothy Bowler, Jean-François Baurain, Oliver Bechter, Axel Hauschild, Marcus O. Butler, Leonel Hernandez-Aya, Lisa Licitra, Rogerio I. Neves, Emily S. Ruiz, Frank Seebach, David M. Weinreich, George D. Yancopoulos, Israel Lowy, Priscila Goncalves, Matthew G. Fury. Primary analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT165.

Many of the volunteer activities required to raise public awareness on skin cancer screening and prevention are supported by dermatological societies and volunteer dermatologists, and are framed by substantial voluntary groups, often not sufficiently credited for their contribution, including blood donors and Red Cross Samaritans. We herein propose that amid the ongoing pandemic, skin cancer screening and blood donations must not be disrupted with attention paid to patient safety foremost. Although efforts over the last decade have led to a significant reduction in skin cancer, ongoing activities have been suspended and, in many cases, disrupted since the coronavirus disease 2019 (COVID-19) spread has created a Public Health Emergency of International Concern. International Health systems are burdened, and patients ignore symptoms and evade specialist visits due to contamination fear of coronavirus, resulting in a 68.61% reduction in skin cancer diagnoses. However, the COVID-19 pandemic has also major implications for blood transfusion. Currently, there are uncertain patterns of demand, and transfusion institutions need to plan for reductions in donations and loss of crucial staff because of sickness and public health restrictions. Supporting volunteer blood donors through voluntary skin cancer screening could be an excellent initiative, bringing people together, giving us the opportunity to abandon the illusion of power and admit our weakness to the ongoing pandemic. Most of us have not worked through pandemics before but it is time to embrace humanity and solidarity via volunteering, with no profit aims but with social goals of equal skin cancer screening opportunities of vitally important volunteer blood donors, encouraging blood donation. In light of a change in dermatology practice, investing in prevention strategies in public health and social protection is the mark of responsible policy action.

A Correction to this paper has been published: https://doi.org/10.1038/s41597-021-00865-3.

Introduction: Primary cutaneous lymphomas (PCL) encompass a heterogeneous group of cutaneous T cell (CTCL) and B cell (CBCL) lymphomas. The scarcity of these clinical entities makes the epidemiological study quite challenging. To date, a few studies of PCL have been conducted in the USA, Europe and Asia. We present epidemiological data of PCL in Greece based on a twelve-year retrospective study. Methods: Our study is based on histology reports from the major haemopathology referral centre in Athens, Greece from 2009 to 2020. Clinical data including the type of lymphoma, date of first diagnosis, age at diagnosis and gender were collected and processed. The patients’ classification is according to the 2018 update of WHO-EORTC classification for PCL. Results: In total, 1171 new cases with PCL have been registered from the 1st of January 2009 to the 31st of December 2020, consisting of 715 males and 456 females, with a male/female ratio of 1.6. The vast majority was CTCL accounting for 83.2% (n=975) of PCL, followed by CBCL with 196 new cases comprising 16.7% of PCL. The male:female ratio was 1.8 for CTCL and 0.9 for CBCL. Mycosis fungoides (MF) was the most common cutaneous lymphoma accounting for 82.3% of CTCL and 68.6% of all PCL (n=803). Classic MF (n=553, 69%) was the most frequent subtype among MF patients followed by folliculotropic MF (n=138, 17.2%). One hundred and twelve patients with MF were presented with atypical forms of the disease. A male predominance was observed among MF patients with 526 newly diagnosed MF in men and 277 in women and a ratio male/female of 1.9. In contrast to the literature, a decreased number of primary cutaneous CD30+ lymphoproliferative disorders was noticed comprising 8.4% of PCL and 10% of CTCL. The most frequent CBCL was the primary cutaneous follicle centre lymphoma (pcFCBCL). Ninety-five new pcFCBCL cases were recorded accounting for 48.4% of CBCL and 8.1% of PCL. The marginal zone lymphoma (pcMZBCL) was the second most common CBCL with 86 new cases representing 43.8% and 7.3% of CBCL and PCL, respectively. Discussion: In the present study, an increasing trend for PCL was observed through the years. This increase may reflect the improvements in the detection and classification of these lymphomas in conjunction with an increase of the underlying causative agents. It is noteworthy that in 2020, during the COVID-19 era, there was a downward trend in new PCL diagnoses, mainly those of MF, whilst the diagnoses of CBCL were steady. While the COVID-19 pandemic may be held responsible for this, other reasons may be implicated and it needs further monitoring over the next few years. This report will empower the comparison with epidemiological data of PCL from other countries and the observation of the diagnostic trend contributing to the investigation of pathogenesis of the disease and novel therapies in the near future.

Restrictive measures due to COVID-19 outbreak resulted in unprecedented modifications in healthcare services and social life. We reviewed records from two referral centres in Greece to identify newly diagnosed cases of gonorrhoea and syphilis from 1 March 2020 to 30 October 2020 and compared them with the respective numbers of the same period in 2019. The total number of new syphilis and gonorrhoea diagnoses in 2020 was 423 versus 521 in 2019. Syphilis cases in 2020 were significantly lower compared with 2019 (306 vs 340, respectively, p=0.02, 10% reduction). Similarly, there were 113 versus 179 gonorrhoea cases in 2020 …

Background: Immune checkpoint inhibitor (ICI)–mediated psoriasis poses significant diagnostic and therapeutic challenges. Objective: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. Methods: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. Results: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P =.03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P

Summary Background Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy. Methods We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov , NCT03132636 , and is no longer recruiting new participants. Findings Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8–18). An objective response per independent central review was observed in 26 (31%; 95% CI 21–42) of 84 patients, including two partial responses that emerged at tumour assessments before the data cutoff and were confirmed by tumour assessments done subsequent to the data cutoff. The best overall response was five (6%) patients with a complete response and 21 (25%) with a partial response. Grade 3–4 treatment-emergent adverse events occurred in 40 (48%) of 84 patients; the most common were hypertension (four [5%] of 84 patients) and colitis (four [5%]). Serious treatment-emergent adverse events occurred in 29 (35%) of 84 patients. There were no treatment-related deaths. Interpretation Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy. Funding Regeneron Pharmaceuticals and Sanofi.

Background HHIs, vismodegib and sonidegib, are approved for treatment of patients with mBCC or locally advanced BCC who are not candidates for surgery or radiation. There is no approved option for patients who progress on or are intolerant to HHIs. Cemiplimab is an anti-programmed cell death-1 monoclonal antibody approved for treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Here we present the prespecified interim analysis of the mBCC cohort from the pivotal Phase 2, non-randomized, multi-center study of cemiplimab in patients with advanced BCC who discontinued HHI therapy due to disease progression, intolerance, or no better than stable disease after 9 months (NCT03132636). Methods Patients with mBCC (nodal and/or distant) received cemiplimab 350 mg intravenously every 3 weeks; interim analysis included patients with the opportunity to be followed for approximately 57 weeks. The primary endpoint was objective response rate (ORR) per independent central review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results In this interim efficacy analysis of 28 patients, 82.1% were males and median age was 65.5 years (range 38−90). Six patients had a partial response, per ICR, for an ORR of 21.4% (95% CI, 8.3, 41.0). ORR per investigator assessment was 28.6% (95% CI, 13.2, 48.7). Among responders, observed DOR was 9−23 months. Median time to response per ICR was 3.2 months (range, 2.1−10.5). Median Kaplan–Meier (KM) estimation of PFS was 8.3 months. Median DOR had not been reached and median KM estimation of OS was 25.7 months. All six responses had observed durations of at least 8 months. The disease control rate was 67.9% (95% CI, 47.6, 84.1).The most common treatment emergent adverse events (TEAEs) regardless of attribution were fatigue (50.0%), diarrhea (35.7%), pruritus (25.0%), and constipation (25.0%). Hypertension (n=2) was the only Grade ≥3 TEAE regardless of attribution occurring in ≥2 patients. TEAEs leading to death occurred in one (3.6%) patient who died from staphylococcal pneumonia, considered unrelated to study treatment. Conclusions This interim analysis demonstrates that cemiplimab is the first agent to provide clinically meaningful anti-tumor activity, including durable responses, in patients with mBCC after progression or intolerance on HHI therapy. Acknowledgements Editorial acknowledgment: Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Ethics Approval The study protocols and all amendments were approved by the institutional review board at each participating study site. The study was conducted in accordance with the principles of the Declaration of Helsinki and with Good Clinical Practice guidelines as defined by the International Conference on Harmonization. All patients provided written informed consent before enrollment.

Keratinocyte carcinoma (KC) is the most common malignancy in white skinned populations. Metformin one of the most commonly prescribed drugs and has been reported to protect against solid cancers. The association between metformin and KC has not been studied in patients at high risk for a subsequent KC. The purpose of this study is to evaluate the association between metformin and KC development in high-risk patients. We performed a secondary analysis of patients enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial to compare risk for KC development between metformin users and non-users. Metformin-users compared to non-users had a significantly lower risk for squamous cell carcinoma with an adjusted Hazard ratio (HR): 0.45, (CI: 0.24-0.84, P < .01) and basal cell carcinoma (HR: 0.70, CI: 0.49-0.97, P < .03). Patients at high risk might benefit from metformin use against a subsequent KC.

One of the major functions of human skin is to provide protection from the environment. Although we cannot entirely avoid, for example, sun exposure, it is likely that exposure to other environmental factors could affect cutaneous function. A number of studies have identified smoking as one such factor that leads to both facial wrinkle formation and a decline in skin function. In addition to the direct physical effects of tobacco smoke on skin, its inhalation has additional profound systemic effects for the smoker. The adverse effects on the respiratory and cardiovascular systems from smoking are well known. Central to the pathological changes associated with smoking is the elastic fibre, a key component of the extracellular matrices of lungs. In this study we examined the systemic effect of chronic smoking (>40 cigarettes/day; >5 years) on the histology of the cutaneous elastic fibre system, the nanostructure and mechanics of one of its key components, the fibrillin-rich microfibril, and the micromechanical stiffness of the dermis and epidermis. We show that photoprotected skin of chronic smokers exhibits significant remodelling of the elastic fibre network (both elastin and fibrillin-rich microfibrils) as compared to the skin of age- and sex-matched non-smokers. This remodelling is not associated with increased gelatinase activity (as identified by in situ zymography). Histological remodelling is accompanied by significant ultrastructural changes to extracted fibrillin-rich microfibrils. Finally, using scanning acoustic microscopy, we demonstrated that chronic smoking significantly increases the stiffness of both the dermis and the epidermis. Taken together, these data suggest an unappreciated systemic effect of chronic inhalation of tobacco smoke on the cutaneous elastic fibre network. Such changes may in part underlie the skin wrinkling and loss of skin elasticity associated with smoking. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.