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Background: Dermatological health-related quality of life (HRQoL) in solid organ transplant recipients (SOTRs), often affected by skin cancer, has been insufficiently explored. This study aimed to evaluate the impact of skin cancer on quality of life (QoL) in SOTRs and to compare HRQoL measures between SOTRs with and without skin cancer. Methods: This cross-sectional study (June 2023–March 2024) assessed adult SOTRs using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. For SOTRs with keratinocyte carcinoma (KC), the Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) questionnaire was also administered. Results: A total of 150 adult SOTRs were included, with 82 having developed post-transplant skin cancer, including melanoma and KCs. DLQI scores were higher in SOTRs with skin cancer, however, the difference was not statistically significant (P ≥ 0.065). SOTRs with skin cancer had higher total Skindex-29 scores (P = 0.012) and "emotion" subscale scores (P = 0.0049), indicating a negative impact on QoL. BaSQoL scores showed a moderate negative effect on QoL, with a higher number of KCs correlating with lower QoL (P < 0.05). Female gender was associated with higher DLQI and BaSQoL diagnosis and treatment scores (P < 0.05). Conclusions: SOTRs with skin cancer had lower QoL, with greater cancer burden linked to worse outcomes. Female gender was also associated with lower QoL. Tailored management strategies are crucial for this population. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed <21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. The burden of KC in CCS remains high, but predictable risk factors should guide screening. [ABSTRACT FROM AUTHOR]

Residual tumor is not always clinically apparent following biopsy of cutaneous carcinomas, which may prompt patients to question the need for definitive treatment. We investigated the percentage of cases in which residual tumor was histologically present at the time of Mohs micrographic surgery (MMS) for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) and investigated factors associated with residual tumor. We examined 483 MMS cases performed for biopsy-proven BCC (n = 287) and SCC (n = 196) between October 2022 and April 2023. Single-stage MMS specimens were step-sectioned en face to exhaust the block. Univariate and multivariable logistic regression models were created. Residual tumor was identified in 83.3% of BCC and 66.8% of SCC at the time of MMS (P =.01). In patients clinically appearing tumor-free following biopsy, residual histologic tumor was identified in 68.2% of BCC and 41.5% of SCC. Residual tumor was significantly more likely in men (P =.04), high-risk sites (P =.002), smaller biopsy sizes (P =.0003), and larger preoperative sizes (P <.0001). Single center, retrospective cohort. The majority of patients with BCC and SCC have residual histologic tumor at the time of MMS, oftentimes even when tumor is not clinically apparent. Multiple factors impact the presence/absence of residual tumor. [ABSTRACT FROM AUTHOR]

Nonmelanoma skin cancer (NMSC) represents the most prevalent form of skin cancer globally, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common types. The search for effective chemopreventive and therapeutic agents has led to the exploration of natural compounds, among which resveratrol (RES), a polyphenolic phytoalexin found in grapes, berries, peanuts, and red wine, has garnered significant attention. This comprehensive review aims to elucidate the effects of RES on NMSC, focusing on its mechanisms of action, efficacy in preclinical studies, and potential as a chemopreventive and therapeutic agent. RES exhibits promising chemopreventive and antineoplastic capabilities against NMSC through various mechanisms, including the induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and anti‐inflammatory activities. Studies have demonstrated that RES can significantly enhance the effectiveness of traditional chemotherapeutic agents, such as 5‐fluorouracil (5‐FU), by inhibiting cellular proliferation and inducing apoptosis in cancerous cells. Furthermore, resveratrol's antioxidant properties may mitigate the impact of reactive oxygen species (ROS) triggered by UV exposure, thus reducing DNA damage and mutations associated with skin cancer development. In vitro and in vivo experiments have shown that RES can effectively hinder the growth and spread of various tumor cell types, including human cutaneous SCC A431 cells, and induce apoptosis. The development of advanced delivery systems, such as nanostructured lipid carriers and liposomes, has been recognized for their potential to enhance the therapeutic effects of RES, particularly its anticancer properties. In conclusion, RES presents a viable candidate for the prevention and treatment of NMSC, owing to its multifaceted mechanisms of action, including its ability to regulate oxidative stress, trigger apoptosis, and inhibit proliferation. However, further clinical studies are required to fully understand its effectiveness and safety in humans, as well as to optimize delivery methods for improved bioavailability and therapeutic outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND Hypertension affects 25%–30% of the world population. Hydrochlorothiazide (HCTZ) is among the most used and cheapest medications but was in 2018 labeled with a warning stating the increased risk of nonmelanoma skin cancer (NMSC). This study describes geographical differences in the association between HCTZ and NMSC from the perspective of hypertensive heart disease (HHD). METHODS We conducted a systematic literature search (PubMed, Embase, Clinicaltrial.gov, and Clinicaltrial.eu) using PICO/PECO acronyms, including case–control, cohort, and randomized controlled trials. We constructed a rate ratio of disability-adjusted life years (DALY) for HHD/NMSC in the global burden of disease (GBD) regions. RESULTS No increased risk of NMSC with the use of HCTZ was found in Taiwan, India, and Brazil. A small (hazard ratio (HR)/odds ratio (OR) ≤1.5) but significantly increased risk was seen in Canada, the United States, and Korea. An increased risk (1.5< HR/OR ≤2.5) in Iceland, Spain, and Japan and a highly increased risk (HR/OR >2.5) in the United Kingdom, Denmark, the Netherlands, and Australia. HHD is associated with a more than tenfold DALY rate compared with NMSC in 13 of 21 GBD regions, corresponding to 77.2% of the global population. In none of these 13 regions was there an increased risk of HCTZ-associated NMSC. CONCLUSIONS Despite limited information from many countries, our data point to large geographical differences in the association between HCTZ and NMSC. In all GBD regions, except Australasia, HHD constitutes a more than fivefold DALY rate compared to NMSC. This disproportionate risk should be considered before avoiding HCTZ from the antihypertensive treatment. [ABSTRACT FROM AUTHOR]

Background: Basal cell carcinoma is the most common nonmelanoma skin cancer, followed by cutaneous squamous cell carcinoma. The objective of the current study was to retrospectively evaluate the epidemiology, characteristic variations, histological aspects, and prognosis of basal cell carcinoma of the facial region based on a single-centre experience. Methods: Data from 125 patients admitted to the Department of Oral and Maxillofacial Surgery, University Medical Center Schleswig-Holstein (UKSH), Kiel, for surgical treatment of basal cell carcinomas of the face between January 2015 and April 2021 were evaluated. Results: The mean patient age was 79.58 years, 60.5% were male and 39.5% were female. Six patients (4.8%) had tumour recurrence with no regional metastasis. Seventy-nine patients (63%) were classified as T1. The nose and the temporal region were the most common areas. The mean tumour thickness was 3.20 mm. Conclusions: Micronodular, sclerosing/morphoeic, nodular, and superficial growth patterns of basal cell carcinoma are highly correlated to recurrence, so an excision safety margin is recommended. There is a strong correlation between tumour thickness and recurrence among basal cell carcinoma cases. When completely excised, the recurrence rate for basal cell carcinoma is relatively low. [ABSTRACT FROM AUTHOR]

Background: Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting Caucasian populations and has been seeing steady increases in incidence globally for decades. Our previous study (from Alberta, Canada) had shown a plateau in the incidence rates for NMSC. This contrasts with data from other regions within Canada and throughout the world that indicated a continued increase in incidence rates of NMSCs. Objectives: The objective of this study was to provide an update on the trends in incidence of NMSC in Alberta, Canada, from 2007 to 2018. Methods: A retrospective analysis of patients from Alberta diagnosed with NMSC from 2007 to 2018 inclusive was conducted with data retrieved from Alberta Cancer Registry. Sex-, age-, anatomical location-, NMSC subtype-, stage-specific incidence rates and trends were examined. Results: From 2007 to 2018, overall incidence rates of NMSC increased by 36%. Invasive squamous cell carcinoma (SCC) and in situ SCC demonstrated the most significant increase, invasive SCC [annual percentage change (APC) 3.48, P =.014] and in situ SCC (APC 5.61, P =.0001). In addition, we were able to determine that females had the most significant increases in NMSC incidence rates from 2007 to 2018 particularly invasive SCC (APC 3.03, P = <.0001) and in situ SCC (APC 5.08, P = <.0001). Conclusions: After initial levelling of NMSC incidence in Alberta in the early part of 21st century, the incidence of NMSC continues to increase over the past decade. The reasons for this change are not clear and likely multifactorial. [ABSTRACT FROM AUTHOR]

Simple Summary: The study examined the number of deaths from nonmelanoma skin cancer (NMSC) in Australia for the fifty years from 1971 to 2021. Australia has the highest reported incidences of NMSC in the world. Deaths from NMSC have been recorded since 1971 and have increased more than five-fold in the 50 years to 2021. There is no sign of a reduction in the increasing incidence of deaths from NMSC. Most deaths from NMSC are due to cutaneous squamous cell carcinoma (SCC). It is estimated that 1 in 260 cutaneous SCCs will metastasize and cause death. The number of non-melanoma skin cancers (NMSC) removed from Australians is increasing every year. The number of deaths from NMSC is increasing but so is the population. However, the population has greatly changed with many dark-skinned people migrating to Australia. These people are at low risk for skin cancer even if they live all their lives in Australia. The susceptible population is the rest of the population. The death rate from NMSC for the entire population and susceptible populations since 1971 is examined in this article. Materials and methods: Data on the Australian population were obtained from the Australian Bureau of Statistics (ABS). Every five years a census is held in Australia and detailed information of the population is provided. The ABS also provided yearly data on the causes of death in Australia. Results: The total population increased from 12,755,638 in 1971 to 25,738,140 in 2021. However, the susceptible population increased by far less, from 12,493,780 to 19,773,783. The number of deaths from NMSC increased from 143 to 765. The crude death rate for the susceptible population increased from 1.1 per 100,000 to 3.9 per 100,000. The crude death rate in the susceptible population aged 65 or more increased from 9.4 to 18.2 per 100,000. Conclusion: Deaths from NMSC are increasing despite public health campaigns to prevent skin cancer. According to current trends, NMSC will cause more deaths than melanoma in Australia. [ABSTRACT FROM AUTHOR]

Objective: One in every three diagnosed malignancies is skin cancer, making it the most prevalent type of cancer in the world. As skin cancer is not commonly reported in Kuwait, this study was conducted to analyze the clinicopathological characteristics of nonmelanoma skin cancers (NMSC), primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), during the last 13 years in a tertiary dermatology center in Kuwait. Materials and Methods: Data were searched for patients with NMSC, primarily BCC and SCC, from 2010 to 2022. A retrospective review was conducted and descriptive data analysis was performed. Results: Of 7,645 cases, a total of 146 patients had NMSC. The patient's average age was 64.9 years. 123 cases (84.2%) had BCC, whereas 23 (15.8%) had SCC. Most of the tumors were seen on the face (35.6%), scalp (20.8%), and nose (17.8%), followed by the back (6.2%), trunk (5.5%), and ear (5.5%). Well-differentiated Cutaneous SCCs were detected in 82.6% of cases. Ulceration was observed in (21.9%) of tumors. The nodular BCC subtype was observed in 50.4% of patients. Conclusion: BCC is the most common type of NMSC detected in Kuwait, with the scalp and face being the most common sites of involvement. Any suspicious lesions should be biopsied to rule out skin malignancy. Highlights of the Study: This is a retrospective and descriptive study that highlights the clinicopathological characteristics of nonmelanoma skin cancer (NMSC) in Kuwait. Most of the tumors were seen on the face and scalp. Traditional clothes worn by men which cover the head and neck regions represent a protective factor from NMSC. [ABSTRACT FROM AUTHOR]

Background/aimIt is estimated that nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans each year. Translation of next-generation sequencing (NGS) data into identification of new potential targets for therapeutic applications may be helpful. Whole-exome sequencing (WES) is a widely used NGS method that involves sequencing the protein-coding regions of the genome.Case reportWe report a case of a 65-year-old female smoker who was found to have two 6 mm lesions in her left nasal vestibule. Biopsies demonstrated synchronous BCC and SCC. The patient underwent surgical excision of both cancers with safe margins followed by plastic reconstruction. WES was performed on both cancers and 16 alterations including BRCA2 (p.P389S), FAM5C (S420L), KMT2A (P855L), and SMO (L412F), as unique for BCC, and 4 alterations including TP53 (p.H179Q) and CDKN2A (p.P114L), as unique for SCC, were identified.ConclusionWe report the first documented case with unique genetic alterations in two distinct and synchronous skin BCC and SCC arising from the same nasal vestibule of a patient. This adds to the growing field of data regarding genetic variants in characterizing malignancies and potentially for targeted therapies.

Despite the importance of patient satisfaction in ensuring high-quality care, studies investigating patient satisfaction in Mohs micrographic surgery (MMS) are limited. We investigated the factors associated with patient satisfaction in MMS for nonmelanoma skin cancer and how patient satisfaction changes in the postoperative period. In this prospective cohort study including 100 patients, patient satisfaction surveys were administered at the time of surgery and at 3 months postsurgery. Sociodemographic characteristics, medical history, and surgical parameters were collected by chart review. Univariate linear and logistic regression models were created to examine these relationships. Decreased satisfaction was observed in patients requiring 3 or more MMS stages both at the time of surgery (P =.047) and at 3 months post-surgery (P =.0244). Patients with morning procedures ending after 1:00 pm had decreased satisfaction at the time of surgery (P =.019). A decrease in patient satisfaction between the time of surgery and 3 months postsurgery was observed in patients with surgical sites on the extremities (P =.036), larger preoperative lesion sizes (P =.012), and larger defect sizes (P =.033). Single-institution data, self-selection bias, and recall bias. Patient satisfaction with MMS is impacted by numerous factors and remains dynamic over time. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy, after basal cell carcinoma (BCC). Photodynamic therapy (PDT) involves converting a photosensitizer to reactive oxygen intermediates, which preferentially bind to hyperproliferative tissue. The most commonly used photosensitizers are methyl aminolevulinate and aminolevulinic acid (ALA). Presently, ALA‐PDT is approved in the US and Canada for the treatment of actinic keratoses on the face, scalp, and upper extremities. Aims: This cohort study evaluated the safety, tolerability, and efficacy of aminolevulinic acid, pulsed dye laser, and photodynamic therapy (ALA‐PDL‐PDT) for treatment of facial cutaneous squamous cell carcinoma in situ (isSCC). Methods: Twenty adult patients with biopsy‐confirmed isSCC on the face were recruited. Only lesions 0.4–1.3 cm in diameter were included. Patients underwent two treatments with ALA‐PDL‐PDT spaced 30 days apart. The isSCC lesion was then excised 4–6 weeks following the second treatment for histopathological assessment. Results: No residual isSCC was detected in 17/20 (85%) patients. Two of the patients with residual isSCC had skip lesions present that explained the treatment failure. Excluding the patients with skip lesions, the posttreatment histological clearance rate was 17/18 (94%). Minimal side effects were reported. Limitations: Our study was limited by small sample size and lack of long‐term recurrence data. Conclusions: The ALA‐PDL‐PDT protocol is a safe and well‐tolerated treatment option for isSCC on the face, providing excellent cosmetic and functional results. [ABSTRACT FROM AUTHOR]

The number of Mohs stages needed to remove a keratinocyte carcinoma affects resource use, expenses, and repair complexity. This study aimed to identify clinicopathological predictors associated with increased or decreased stages and areas for further research. A retrospective review was conducted from a single private practice with two Mohs surgeons of 2788 consecutive Mohs cases between January 2017 and December 2021, analyzing the average number of stages taken versus national norms (P = 0.21) and subgroups using unpaired t tests (*<0.05). Several tumor features were significantly associated with fewer stages: squamous cell carcinomas, Mohs appropriate use criteria score of 7 or 8, preoperative size <0.25 cm2, tumors on the lips and extremities (including hands/fingers), and smoking. Clinicopathological features significantly associated with more stages included Mohs appropriate use criteria score of 9, recurrent skin cancers, basal cell carcinomas, tumor size of 2.25–3.99 cm2, cancers on ears, solid organ transplant patients, treatment delays >180 days, and patients ≥90 years old. Significant predictors exist for both increased and decreased numbers of Mohs micrographic surgery stages required to eradicate a tumor, which may help Mohs surgeons facilitate, plan, and allocate resources more effectively. Areas for further research in Mohs micrographic surgery are identified. [ABSTRACT FROM AUTHOR]

Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80 years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. Study patients were predominantly White and from a single institution, limiting the generalizability of results. Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up. [ABSTRACT FROM AUTHOR]

Background: The possible correlation between melanoma and Parkinson's disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary. Methods: From 2004 to 2017, a retrospective analysis of the centre's database was performed based on International Statistical Classification of Diseases-10 codes. Results: Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47-0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56-0.98, p=0.0392) but not for melanoma. Conclusions: We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population. [ABSTRACT FROM AUTHOR]

The vast majority of skin cancers can be classified into two main types: melanoma and keratinocyte carcinomas. The most common keratinocyte carcinomas include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Multiple familial syndromes have been identified that can increase the risk of developing SCC, BCC, and/or melanoma. The major syndromes include oculocutaneous albinism for SCC, basal cell nevus syndrome for BCC, familial atypical multiple mole-melanoma syndrome, and hereditary breast and ovarian cancer syndrome for melanoma. In addition, familial syndromes that can predispose individuals to all three major skin cancers include xeroderma pigmentosum and Li–Fraumeni syndrome. This review highlights the epidemiology, risk factors, pathogenesis, and etiology of the major and minor syndromes to better identify and manage these conditions. Current investigational trials in genomic medicine are making their way in revolutionizing the clinical diagnosis of these familial syndromes for earlier preventative measures and improvement of long-term prognosis in these patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Solid organ transplant recipients (SOTRs) are at increased risk of skin cancer and suffer from greater disease-specific morbidity and mortality. To risk stratify the expanding SOTR population for more targeted skin cancer screening, a detailed understanding of risk factors is needed. Using combined clinical and pathological data to capture prevalence of actinic keratosis (AK) and skin cancer, this study aimed to identify risk factors of skin cancer development in a Danish SOTR cohort. Methods: The trial comprised a retrospective cohort study of patients attending organ transplant clinics at the dermatological departments of Bispebjerg and Gentofte Hospitals in Copenhagen, Denmark, between 2009 and 2021. In addition to pathology records, AK prevalence was determined by review of electronic medical records (EMRs) of SOTR visits which specifically included descriptions of clinical AK. Prevalence of skin cancer, here defined as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) (invasive or in situ), or melanoma (invasive or in situ), was determined by EMR and pathology code review. Additional data extracted from EMRs included age, sex, Fitzpatrick skin type, transplantation date and type, and immunosuppressive therapy. The effect of risk factors on skin cancer was calculated by Cox proportional hazards regression. Results: A total of 822 SOTRs were included with a mean follow-up duration of 10.8 years (SD 2.4 years). A skin dysplasia diagnosis was identified in 30% (n = 250) of the population, consisting of either AK (22%; n = 177), skin cancer (23%; n = 186) or both (14%; n = 113). An AK diagnosis predicted both SCC (odds ratio [OR]: 31.5 [95% CI: 9.8–100.6], p < 0.0001) and BCC development (OR: 2.3 [95% CI: 1.6–3.3], p < 0.0001), with AKs diagnosed an average 3.1 years before the first SCC (p < 0.0001). Correspondingly, while the risk of SCC in SOTRs without AK was 1.4% 25 years after transplantation, SOTRs with AKs had a 23% SCC risk only 10 years posttransplant. Other identified risk factors included Fitzpatrick skin type I (BCC: OR: 2.4 [95% CI: 1.2–5.0], p = 0.018; SCC: 3.2 [95% CI: 1.2–8.2], p = 0.016) and transplantation duration >15 years (BCC: OR: 1.8 [95% CI: 1.2–2.7], p = 0.007). No significant association between skin cancer development and sex or immunosuppressive regimen was shown. Conclusion: Keratinocyte carcinoma is strongly associated with an AK diagnosis in SOTRS and should prompt intensified skin cancer screening in affected individuals. [ABSTRACT FROM AUTHOR]

Background/Objective: A history of keratinocyte carcinoma (KC) is a risk factor for further KCs, but population‐based studies quantifying the risk are lacking in Australia. We aimed to describe the risk of subsequent KCs after first KCs in the Australian state of Tasmania. Methods: Tasmanian residents identified in the Tasmanian Cancer Registry with a first histologically confirmed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or synchronous BCC and SCC (within 3 months) between January 1985 and December 2013 were followed up for at least 5 years for the development of a subsequent KC. Cumulative risk, incidence rates and standardised incidence ratios (SIRs) were calculated. Results: Those first diagnosed with BCC‐only, SCC‐only or synchronous BCC and SCC had (i) 5‐year cumulative risks of subsequent KCs of 32%, 29% and 51%, (ii) annualised 5‐year incidence rates of 8100/100,000 person‐years at risk (PYR), 7747/100,000 PYR and 16,634/100,000 PYR and (iii) SIRs of 10.6 (95% CI: 10.5–10.6), 12.5 (95% CI: 12.4–12.6) and 313.0 (95% CI: 305.2–321.1), respectively. Risk estimates increased substantially when multiple (two or more) lesions of any type were diagnosed synchronously. Conclusions: In the first Australian population‐based study to describe the risk of subsequent KCs according to histological types, around one in three Tasmanians diagnosed with first KCs were diagnosed with subsequent KCs within 5 years. The risk of subsequent KCs was higher among those with a history of multiple synchronous lesions, especially if they included both BCC and SCC lesions. [ABSTRACT FROM AUTHOR]

Introduction/Background Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, are associated with prolonged intermittent sun exposure (specifically ultraviolet radiation). Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with multiple comorbidities.1,2 While AD is associated with an increased risk of skin cancers,3 data on the underlying risk of NMSC in patients with AD are inconsistent.1 Objective To evaluate NMSC incidence and risk in patients with AD compared with a non-AD matched control cohort and patients with rheumatoid arthritis (RA). To evaluate the effect of disease activity, analyses were repeated in patient subgroups with moderate-to-severe disease. Methods This retrospective observational study used US claims data from the Optum Clinformatics Data Mart. Eligible patients were aged ≥ 18 years with diagnosed AD (≥ 2 claims for AD or ≥ 1 claim for AD or eczema with asthma and/or hay fever, food allergies, or allergic rhinitis) between March 2017–March 2023. The cohort entry date was the date of the first qualifying disease diagnosis. Patients were classified as having moderate-to-severe disease if they received dupilumab for AD or advanced systemic therapy for RA during follow-up. Comparator groups included non-AD control cohorts (matched 1:1 to the AD and moderate-to-severe AD cohorts, respectively, by age [± 1 year], sex, and cohort entry date), patients diagnosed with RA (≥ 2 claims ≥ 7 days apart filed by a rheumatologist), and patients with moderate-to-severe RA. Crude NMSC incidence rates were reported. Relative risk was calculated using multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications. Results This analysis included data from 391,753 patients with AD (7136 with moderate-to-severe AD) and 97,445 patients with RA (35,846 with moderate-to-severe RA). The matched AD and non-AD cohorts each included 381,221 patients. The matched moderate-to-severe AD and non-AD cohorts each included 7134 patients. The mean (SD) age in years was 58.1 (18.8) for AD and non-AD cohorts after matching and 67.0 (13.6) for RA. The median (IQR) follow-up time in days was 1087 (487–1485) for AD, 1218 (548–1782) for RA, and 1013 (376–1562) for non-AD controls. The NMSC incidence per 100 patient-years (95% CI) was 2.12 (2.10, 2.15) for AD and 1.74 (1.72, 1.77) for matched non-AD controls, 2.11 (1.87, 2.35) for moderate-to-severe AD and 1.28 (1.10, 1.47) for matched non-AD controls, 2.33 (2.28, 2.38) for RA, and 2.03 (1.94, 2.12) for moderate-to-severe RA. The relative NMSC risk (adjusted hazard ratio [95% CI]) was greater in patients with AD vs matched non-AD controls (1.32 [1.30, 1.35]) and moderate-to-severe AD vs matched non-AD controls (1.36 [1.12, 1.65]. There was no significant difference in NMSC risk in patients with AD compared with RA (1.03 [1.00, 1.06]) or moderate-to-severe AD compared with moderate-to-severe RA (0.97 [0.87, 1.08]). On average, NMSC risk was > 6 times higher in patients with AD with a history of NMSC vs those without; history of other malignancies and organ transplantation were also associated with increased NMSC risk. NMSC risk was ≥ 35% lower in patients who were female vs male, and patients who were Asian, Hispanic, or Black vs White. Conclusions Patients with AD demonstrated a higher NMSC risk compared with non-AD matched controls, and a similar NMSC risk compared with patients with RA; patterns were consistent for patients with moderate-to-severe disease. NMSC risk was higher in patients with AD with a history of NMSC or other malignancies. As a limitation, patients with AD were commonly examined by dermatologists who were likely to look for and find NMSC. Characterizing the underlying NMSC risk among patients with AD may inform treatment benefit-risk assessments. [ABSTRACT FROM AUTHOR]

Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case–control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. These are high-quality registers which include all cancer diagnoses, as well as every prescription in the country. Cases included all first-time histologically confirmed diagnoses of (BCC), in situ squamous cell carcinoma (SCCis) and invasive SCC between 2003 and 2017. Each case was paired with 10 age- and sex-matched controls. Multivariate conditional logistic regression analysis was performed. Four thousand seven hundred patients with BCC, 1167 patients with SCCis and 1013 patients with invasive SCC were identified and paired with 47,292, 11,961 and 10,367 controls, respectively. Overall statin use was associated with an increased risk of invasive SCC and SCCis but not BCC (adjusted OR [95% CI]: 1.29 [1.11–1.50]; 1.43 [1.24–1.64]; 1.03 [0.95–1.12], respectively). Subgroup analysis demonstrated that statins were significantly associated with invasive SCC and SCCis in patients over 60, but not in those under 60. Atorvastatin was only associated with an increased risk of SCCis; whereas, simvastatin was associated with an increased risk of both invasive SCC and SCCis. This whole-population study of Iceland demonstrates that statin exposure is associated with increased risk of SCC, but not BCC, in a low UV environment. The reasons are unclear, but our results may suggest that individuals receiving atorvastatin and simvastatin have differing levels of baseline keratinocyte cancer risk or that properties of a statin other than 'statin intensity' affect association with SCC. [ABSTRACT FROM AUTHOR]

Nonmelanoma skin cancers (NMSCs) are the most common malignancies worldwide. Millions of new cases every year present challenge to healthcare systems. Recent years brought numerous new data concerning high dose rate (HDR) brachytherapy (BT) as treatment option for NMSCs. International guidelines do not recognize BT as a method of choice given lack of randomized trials, however many prospective and retrospective studies show promising results. Aim of the study was to present the efficacy of HDR BT, with analysis of its safety and adverse effects based on review of the English published medical full‐text papers. Literature review of 13 articles published between 1999 and 2021 was performed. Pubmed and Google Scholar databases were searched on October 2021 using keywords: ([Basal cell carcinoma] OR [squamous cell carcinoma] OR [non‐melanoma skin cancer]) AND (HDR brachytherapy). Fourteen full‐text English articles with follow up over 1 year and study group over 50 patients were included into analysis. In analyzed material, 2403 patients received HDR BT. Local control varied between 71% and 99%.Dominant reported cosmetic effect was good or very good. Results were cross‐referenced with recent meta‐analyses comparing BT to surgical excision, Mohs microsurgery and external beam radiotherapy. Radiodermitis is the main adverse effect of radiation treatment during and after radiotherapy. HDR BT emerges as potentially noninferior treatment method providing very good reported cosmetic outcomes. [ABSTRACT FROM AUTHOR]

Hydroxyurea therapy is commonly used in the treatment of patients suffering from myeloproliferative diseases, such as polycythemia vera. It is supported by evidence that this type of therapy can generate mild skin lesions like leg ulcers, erythema, and hyperpigmentation. There are also some studies that show an increased risk of development of nonmelanoma skin cancers. We report a 56-year-old man with a 13-year history of polycythemia vera, treated chronically with hydroxyurea. In April 2020, the patient presented a skin lesion on the forehead, skin horn on the left forearm, and hyperkeratosis on the rims of both ears. In the patient’s history, in October 2019, complete excision of the skin lesion in the central area of the forehead was performed. After 4 months, a new skin lesion appeared at the same area of the forehead, which in May 2020 after resection in the histopathological examination was diagnosed as recurrence of squamous cell carcinoma. The aim of the case is to draw the clinicians’ attention to the increased risk of squamous cell carcinoma and basal cell carcinoma in patients treated with hydroxyurea. Increased vigilance would make it possible to recognize them earlier, and thus potentially reduce the undesirable effects associated with the delayed radical treatment of these skin cancers. Randomized clinical trials assessing the potential benefits of oral retinoids for chemoprevention of nonmelanoma skin cancers in the hydroxyurea-treated population should also be considered.

Background: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory cutaneous disorder typically affecting sun‐damaged skin of mature individuals. Clinical features of EPDS include sterile pustules and chronic crusted erosions that can be hyperkeratotic and lead to scarring alopecia, atrophy, and telangiectasia. While the condition occurs on sun‐damaged skin, a relationship with non‐melanoma skin cancer (NMSC) has not been investigated. Objectives: Here we attempted to identify cases of NMSC developing in the setting of EPDS. Methods: Retrospective review of EPDS cases in a dermatology practice. Results: Six patients with mean (range) age 82 (65–92) years that developed NMSC in the setting of EPDS are reported. Five patients had skin phototype I or II associated with substantial solar elastosis. Four patients had history of NMSC. Four patients developed squamous cell carcinoma and two patients basal cell carcinoma on the scalp in the setting of EPDS. A morphologic change in an EPDS lesion, such as a crusted plaque becoming nodular and/or growing significantly within a relatively short period of time, prompted a biopsy that revealed NMSC. Conclusions: NMSC may develop in the setting of EPDS. Possible mechanisms underlying this association include the chronic inflammation associated with EPDS and ultraviolet light exposure. It is crucial to promptly obtain a biopsy in EPDS cases showing signs suspicious for NMSC. Further studies are required to confirm whether NMSC shows a higher prevalence in the setting of EPDS. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. Methodology: We performed a systematic review and meta-analysis of case–control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). Results: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71–1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. Conclusions: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development. [ABSTRACT FROM AUTHOR]

BackgroundAcantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited.ObjectiveWe sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases.MethodsDefinitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records.ResultsOf 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented.LimitationsThis was a single-institution retrospective study from the United States.ConclusionsThe presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines.

Background: Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer.Case Presentation: We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up.Conclusions: We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Nonmelanoma skin cancers (NMSC) as a group exceed the incidence of all other malignancies combined. NMSC includes basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. As the incidence continues to rise, it is important to appreciate the available treatment options. This article discusses the treatment of NMSC through surgical, topical, regional, and systemic modalities. As there are many treatment options available for these diseases, selection of the appropriate method can be difficult. With time, we expect treatment decisions to become even more complex and personalized. The role of systemic immunotherapies and neoadjuvant therapies in the treatment of NMSC is still not well defined. Local treatment with intralesional injections and isolated limb infusion may prove to be promising alternative therapies. [ABSTRACT FROM AUTHOR]

Background: Clinical trials report occurrence of nonmelanoma skin cancers (NMSCs) with ruxolitinib in patients with polycythemia vera (PV) or myelofibrosis (MF); however, the level of risk and effect of covariates are not known in the real-world setting.Objective: To systematically assess the risk of developing NMSC after ruxolitinib exposure in patients with PV or MF.Methods: A 10-year retrospective cohort of patients with PV or MF at Stanford Medical Center was identified and matched according to age, gender, race, Charlson Comorbidity Index, disease diagnosis, and follow-up time. The main outcome measure was hazard ratio (HR) for NMSC (comprised of basal cell carcinoma and squamous cell carcinoma [SCC]) after ruxolitinib exposure, adjusted for covariates.Results: The study cohort consisted of 564 patients (188 exposed to ruxolitinib for at least 4 weeks, 376 unexposed). Ruxolitinib-exposed patients with PV or MF had an adjusted NMSC HR of 2.69 (95% CI, 1.03-7.02). In particular, ruxolitinib exposure was associated with SCC (HR, 3.24; 95% CI, 1.45-7.22), with non-Janus kinase 2-mutated patients showing even higher SCC risk (HR, 7.40; 95% CI, 2.54-21.63).Limitations: Retrospective design.Conclusions: Our real-world results indicate that SCC risk is increased in patients with PV or MF taking ruxolitinib and support consideration of skin cancer monitoring. [ABSTRACT FROM AUTHOR]

Background: Evidence is controversial and limited concerning whether surgical delays are associated with tumor growth for cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas.Objective: Identify tumor subpopulations that may demonstrate an association between tumor growth and surgical delay.Methods: We retrospectively analyzed 299 SCCs and 802 basal cell carcinomas treated with Mohs surgery at a single institution. Time interval from biopsy to surgery represented surgical delay. Change in major diameter (ΔMD) from size at biopsy to postoperative defect represented tumor growth. Independent predictors of ΔMD were identified by multivariate analysis. Linear regression was then utilized to assess for whether the ΔMD from these independent predictors trended with surgical delay.Results: Surgical delays ranged from 0 to 331 days. Among SCCs, histologic subtype and prior treatment were identified as independent predictors of ΔMD. Significant associations between ΔMD and surgical delay were found for poorly- and moderately-differentiated SCCs, demonstrating growth rates of 0.28 cm and 0.24 cm per month of delay, respectively. The ΔMD for SCCs with prior treatment and basal cell carcinoma subgroups did not vary with surgical delay.Limitations: Retrospective design, single center.Conclusion: Surgical delays of less than a year were associated with tumor growth for higher-grade SCCs, with effect sizes bearing potential for clinical significance. [ABSTRACT FROM AUTHOR]

Background: Keratinocyte carcinomas, particularly squamous cell carcinoma (SCC), occur more frequently and aggressively in solid-organ transplant recipients (SOTRs) than in the general population. Systemic retinoids are effective in secondary prevention of keratinocyte carcinomas in this population, but their use is limited by adverse effects including a rebound effect in cases of treatment discontinuation. Objective: Our aim was to determine whether low-dose acitretin is efficient in the secondary prevention of keratinocyte carcinomas in SOTRs. Methods: This retrospective case-crossover study was conducted at a specialized dermatology clinic for SOTRs in a large transplantation center in 2010–2017. Patients with at least 1 previous keratinocyte carcinoma who were treated with acitretin 10 mg/day for 2 years were included. The main outcome was the difference in the number of new keratinocyte carcinomas diagnosed during treatment compared to during the 2-year pretreatment period. Results: The cohort included 34 SOTRs. A significant reduction in the mean number of new keratinocyte carcinomas during treatment relative to the pretreatment period was observed (1.7 vs. 3.6, –53% p = 0.002). Similar results were noted on analysis by tumor type, for both SCC and basal cell carcinoma. Conclusion: This study of SOTRs demonstrated positive results for low-dose acitretin as a chemoprevention of keratinocyte carcinomas in this population. [ABSTRACT FROM AUTHOR]

Background/Aim: It is estimated that nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans each year. Translation of next-generation sequencing (NGS) data into identification of new potential targets for therapeutic applications may be helpful. Wholeexome sequencing (WES) is a widely used NGS method that involves sequencing the protein-coding regions of the genome. Case Report: We report a case of a 65-year-old female smoker who was found to have two 6 mm lesions in her left nasal vestibule. Biopsies demonstrated synchronous BCC and SCC. The patient underwent surgical excision of both cancers with safe margins followed by plastic reconstruction. WES was performed on both cancers and 16 alterations including BRCA2 (p.P389S), FAM5C (S420L), KMT2A (P855L), and SMO (L412F), as unique for BCC, and 4 alterations including TP53 (p.H179Q) and CDKN2A (p.P114L), as unique for SCC, were identified. Conclusion: We report the first documented case with unique genetic alterations in two distinct and synchronous skin BCC and SCC arising from the same nasal vestibule of a patient. This adds to the growing field of data regarding genetic variants in characterizing malignancies and potentially for targeted therapies. [ABSTRACT FROM AUTHOR]

Hydroxyurea therapy is commonly used in the treatment of patients suffering from myeloproliferative diseases, such as polycythemia vera. It is supported by evidence that this type of therapy can generate mild skin lesions like leg ulcers, erythema, and hyperpigmentation. There are also some studies that show an increased risk of development of nonmelanoma skin cancers. We report a 56-year-old man with a 13-year history of polycythemia vera, treated chronically with hydroxyurea. In April 2020, the patient presented a skin lesion on the forehead, skin horn on the left forearm, and hyperkeratosis on the rims of both ears. In the patient's history, in October 2019, complete excision of the skin lesion in the central area of the forehead was performed. After 4 months, a new skin lesion appeared at the same area of the forehead, which in May 2020 after resection in the histopathological examination was diagnosed as recurrence of squamous cell carcinoma. The aim of the case is to draw the clinicians' attention to the increased risk of squamous cell carcinoma and basal cell carcinoma in patients treated with hydroxyurea. Increased vigilance would make it possible to recognize them earlier, and thus potentially reduce the undesirable effects associated with the delayed radical treatment of these skin cancers. Randomized clinical trials assessing the potential benefits of oral retinoids for chemoprevention of nonmelanoma skin cancers in the hydroxyurea-treated population should also be considered. [ABSTRACT FROM AUTHOR]

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to “a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period”. The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Background: On the basis of high-local recurrence risk features and tissue-rearranging reconstruction, consensus guidelines recommend microscopic margin control for keratinocyte carcinomas (KCs) but not for cutaneous melanoma.Objective: To compare high-local recurrence risk features and frequency of tissue-rearranging reconstruction for head and neck KC with those for melanoma.Methods: Retrospective cohort study of KC versus melanoma treated at the Hospital of the University of Pennsylvania with Mohs micrographic surgery.Results: A total of 12,189 KCs (8743 basal cell carcinomas and 3343 squamous cell carcinomas) and 1475 melanomas (1065 melanomas in situ and 410 invasive melanomas) were identified from a prospectively updated Mohs micrographic surgery database. Compared with KCs, melanomas were significantly more likely to have high-local recurrence risk features, including larger preoperative size (2.10 cm vs 1.30 cm [P < .0001]), recurrent status (5.08% vs 3.91% [P = .031]), and subclinical spread (31.73% vs 26.52% [P < .0001]). Tissue-rearranging reconstruction was significantly more common for melanoma than for KCs (44.68% vs 33.02% [P < .0001]; odds ratio, 1.98 [P < .0001]).Limitations: This was a retrospective study, and it did not compare outcomes with those of other treatment methods, such as slow Mohs or conventional excision.Conclusion: Melanomas of the head and neck have high-local recurrence risk features and require tissue-rearranging reconstruction more frequently than KCs do. [ABSTRACT FROM AUTHOR]