Search

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to identify clarifying immunohistochemical markers, molecular markers, or both. Clinicopathologic data (22 cases) were reviewed. Immunohistochemistry (insulinoma-associated protein 1, BCL-2, mucin 2 [MUC2], mucin 4, androgen receptor, β-catenin, and Merkel cell polyomavirus) and next-generation sequencing (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets, 468 genes) were performed (3 cases). Female patients (n = 15) and male patients (n = 7) (mean age 71.8 years; range 53–88 years) had eyelid or periorbital tumors (>90%) with mucin-containing solid or cystic neuroendocrine pathology. Immunohistochemistry (insulinoma-associated protein 1, BCL2, androgen receptor, retinoblastoma-associated protein 1, and β-catenin) was diffusely positive (5/5), MUC2 partial, mucin 4 focal, and Merkel cell polyomavirus negative. Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets identified 12 single-nucleotide variants and 1 in-frame deletion in 3 cases, each with DNA damage response or repair (BRD4, PPP4R2, and RTEL1) and tumor-suppressor pathway (BRD4, TP53, TSC1, and LATS2) mutations. Microsatellite instability, copy number alterations, and structural alterations were absent. Insulinoma-associated protein 1 and MUC2 are positive in endocrine mucin-producing sweat gland carcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNA damage repair and tumor-suppressor pathways may be implicated.

Background Although basal cell carcinoma (BCC) tends to follow an indolent course, some tumors can exhibit locally aggressive behavior and invade into bone. Objective To analyze all published demographic, clinical, and treatment data on recurrence patterns, disease progression, disease-specific death, and overall mortality of BCC with bone invasion. Methods A systematic review and pooled-survival analysis was performed, including case reports and case series of BCC with bone invasion. Results The study included 101 patients from 70 publications. BCC tumors invading into bone were most often large, neglected tumors located in high-risk face areas. At 5 years, patients had a 30% risk probability of disease recurrence (after negative margins), a 72.1% risk of disease progression or death (with ambiguous margin status), an 18.2% risk of BCC-related death, and a 20.7% overall probability of death. Limitations Limitations include the reliance on case reports and series for individual patient data, which has the potential to introduce selection bias. Conclusion The high rate of disease progression and suboptimal 5-year survival rate highlights the poor prognosis of BCC with bone invasion and further underscores the importance of early detection and treatment.

Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

There is limited literature regarding potential disparities in nonmelanoma skin cancer for patients with skin of color.Use the sizes of Mohs micrographic surgery defects to examine disparities in nonmelanoma skin cancer among Hispanic/Latino patients with a secondary aim to examine the effect of insurance type.We conducted a multicenter retrospective study using data from 3 major institutions in Los Angeles County. A total of 3486 Mohs micrographic surgeries of basal cell, squamous cell, and basosquamous cell carcinomas were analyzed.Mohs micrographic surgery defect sizes were 17% larger among Hispanic/Latino patients compared with non-Hispanic White patients. More notably, when comparing defect sizes of squamous cell carcinomas to those of basal cell carcinomas, defects were 80% larger among Hispanic/Latino patients compared to non-Hispanic White patients who had 25% larger defect sizes. Compared to patients with Medicare, patients with health maintenance organization and Medicaid/health maintenance organization had 22% and 52% larger defect sizes, respectively, whereas patients with preferred provider organization, had 10% smaller defect sizes.The data included were from a single county population.Disparities regarding nonmelanoma skin cancer exist between patients with skin of color and White patients. Patients and the medical community need to be cognizant that skin cancer can develop in patients regardless of their race and ethnicity.

As the United States becomes more diverse, determining differences in health care utilization and costs in the management of skin cancers is fundamental to decision-making in health care resource allocation and improving care for underserved populations.To compare health care use and costs among non-Hispanic White, Hispanic White, and non-Hispanic Black patients with keratinocyte carcinoma.A nationwide cross-sectional study was performed using Medical Expenditure Panel Survey data from 1996 to 2015.Among 54,503,447 patients with keratinocyte carcinoma (weighted) over a 20-year period, 53,134,351 (97%) were non-Hispanic White; 836,030 (1.5%) were Hispanic White; and 170,755 (0.3%) were non-Hispanic Black. Compared to non-Hispanic White patients, Hispanic White patients had significantly more ambulatory visits per person per year (5.4 vs 3.5, P = .003). Compared to non-Hispanic White patients, non-Hispanic Black patients had significantly more ambulatory visits (13.1 vs 3.5, P = .027) and emergency department visits (2.3 vs 1.1, P .001), and incurred significantly higher ambulatory costs ($5089 vs $1131, P = .05), medication costs ($523 vs $221, P = .022), and total costs per person per year ($13,430 vs $1290, P = .032).Data for squamous cell carcinomas and basal cell carcinomas are combined.Keratinocyte carcinoma was more costly to treat and required more health care resources in non-Hispanic Black and Hispanic White patients than in non-Hispanic White patients.

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.

Basaloid follicular hamartoma is a benign, superficial malformation of hair follicles that can be mistaken both clinical and histopathologically for basal cell carcinoma. Basaloid follicular hamartoma has been linked to a mutation in the PTCH-1 gene, which is part of the same pathway involved in Gorlin-Goltz syndrome. Here we present a 9-year-old patient with an asymptomatic congenital lesion on the forehead, which increased in size over the years. Histopathology showed a basaloid follicular hamartoma associated with follicular mucinosis and inflammation. Gorlin-Goltz syndrome was ruled out by clinical examination.

Basaloid squamous cell carcinoma (BSCC), a histologically distinctive variant of squamous cell carcinoma comprising basal cell carcinoma and squamous cell carcinoma, is aggressive and shows a poor prognosis because of frequent lymph node invasion and distant metastases. To date few articles regarding chemotherapy for metastatic disease have been reported, thus feasible chemotherapy is not well established. Cetuximab is a monoclonal antibody for epithelial growth factor receptor (EGFR), which has great efficacy for head and neck squamous cell carcinoma due to EGFR signaling pathway blockage. Because BSCC also highly expresses EGFR, cetuximab may be effective for BSCC. We report here a first case of recurrent BSCC in the ethmoid sinus with intracranial extension treated with cetuximab-based chemotherapy, which revealed great response in a 40-year-old man. Positron emission tomography (PET) revealed no lymph node or distant metastasis. The patient underwent chemoradiotherapy 66 Gy in 33 fractions with triweekly 100 mg/m2 cisplatin. However, 12 weeks after treatment completion PET revealed a residual tumor at the primary cancer site. Combination therapy with weekly paclitaxel and cetuximab was started, and complete response was observed 2 months from treatment initiation. The patient has maintained complete response for 32 months, and no tumor regrowth has been observed.

Summay Introduction Squamous cell carcinoma of the ear (SCC-E) shows high rates of local recurrence (LR) and lymph node metastases (NM). SCC-E is the leading cause of death from nonmelanoma skin cancer. Objective To determine the LR and NM rates and survival after Mohs micrographic surgery (MMS). Patients and methods We treated 170 invasive SCC-E with MMS with a mean follow up of 48 months. Mean age was 76 years, 93.2% were male patients, mean size: 1.5 cm, and 61.8% of the tumours were well differentiated. Results We observed 5 LRs, 2 locoregional recurrences, and 16 NMs in 23 patients. LR and NM rates were 4.1% and 10.6%, respectively. Only 3/25 recurrences occurred after 2 years of follow up. We observed 1(0.6%) distant metastasis (DM) in a patient who also presented LR + NM. Six out of seven cases with LR and 8/18 with NM died of disease, regardless of aggressive surgical rescue with or without adjuvant radiotherapy. Five-year overall survival, disease-free survival, and disease-specific survival were 81%, 82.6%, and 89.7%, respectively. Conclusions Undeniably, the outcome in SCC-E is determined by locoregional control. DM are sporadic and rarely the cause of death. Systematic reviews and retrospective studies show a solid trend in favor of MMS vs surgical excision. The LR rate of this series (4.1%) is one of the lowest published to date with regard to SCC-E, and confirms this assertion. We observed 10.6% NMs according to other series that treated the whole spectrum of SCC-E. Almost 2/3 of patients with NMs die after therapeutic rescue. We believe that it is essential to identify prognostic factors to select patients for one of the following: close surveillance (ultrasonography) during the first 2 years after surgery, sentinel node biopsy, or elective treatment of the nodes (surgery or radiotherapy).

Background Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results. Objective To systematically review the prevalence of dermoscopic structures in BCC and its subtypes. Methods Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes. Results Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC. Limitations Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions. Conclusion In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.

Trichoblastoma (TB) is an uncommon benign follicular tumour for which clinical data is limited since most reports originate from pathology studies.To describe the clinical aspects of TB.This is an ancillary study of a prospective multicentre cohort of 2710 clinically suspected basal cell carcinoma (BCC), including 935 nodular BCCs. Sixty-two cases were TB: they were analysed and compared to 935 nodular BCCs.TB mostly occurred in females (61% vs. 43% for BCC, P0.01) of mean age 63 years. They were located on the head and neck, mainly on the nose and forehead, in 87% of cases. The mean size was 8.1mm, 77% were10mm (55% of BCCs, P0.001), 8% were ulcerated (vs. 21% of BCCs, P0.02), and 47% persisted for more than 1 year (34% of BCCs, P0.05). Most cases had a clinical presentation similar to nodular BCC, except for 5 small, flat, white papules and 1 anfractuous plaque.Cases originated from a series of tumours clinically suspected as BCCs.Some 2.6% of tumours clinically diagnosed as BCC are in fact TB. TB occurs on the head, are more frequent in women, and are smaller and of longer duration than BCC. In most cases, clinical diagnosis on clinical grounds is difficult.

Despite approximately 4400 locally advanced US cases annually, high-stage basal cell carcinoma (BCC) is ill-defined.To develop a tumor (T) staging system for BCC that will predict metastasis/death and compare its performance with that of the American Joint Committee on Cancer 8th edition (AJCC8) T-staging system.Brigham and Women's Hospital (BWH) T staging was developed from a previously published nested cohort of 488 primary BCCs. Tumors were staged via BWH and AJCC8 T-staging systems, and predictions of metastasis and/or death were compared.The BWH and AJCC8 T-staging systems both captured all metastases/deaths in high T stages (BWH, T2; AJCC8, T3/T4). BWH T2 included 54% fewer cases ≥2 cm than AJCC8 T3/T4. BWH had a higher specificity (0.92 vs 0.80; P .001) and positive predictive value (24% vs 11%, P .001) for identifying cases at risk for metastasis/death, and the C-statistic was superior for BWH (P .001). The BWH T2 10-year cumulative incidence of metastasis/death was 37% (95% confidence interval, 21%-60%).Two-center cohort.BWH and AJCC 8 BCC staging both capture all metastases and deaths in the upper stages. However, BWH staging does so in half the number of cases, thus minimizing inappropriate up-staging. The risk of metastasis or death in BWH T2 BCC is sufficient to warrant surveillance for recurrence and clinical trials of adjuvant therapy.

Radiation therapy may be performed for a variety of cutaneous malignancies, depending on patient health status, tumor clinical and histologic features, patient preference, and resource availability. Dermatologists should be able to recognize the clinical scenarios in which radiation therapy is appropriate, as this may reduce morbidity, decrease risk of disease recurrence, and improve quality of life. The second article in this 2-part continuing medical education series focuses on the most common indications for radiation therapy in the treatment of basal cell carcinoma, cutaneous squamous cell carcinoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi sarcoma, angiosarcoma, cutaneous lymphoma, melanoma, undifferentiated pleomorphic sarcoma, and sebaceous carcinoma.

Background Liver transplant recipients are at lifelong risk of immunosuppression-related cutaneous complications, such as malignancy and infection. Objective Our study aims to assess the epidemiology of dermatologic conditions among liver transplant recipients in an academic medical center in Singapore. Methods Medical records of liver transplant recipients on follow-up with gastroenterology and dermatology departments at the Singapore General Hospital between 2006 and 2021 were retrospectively reviewed. A literature review was subsequently performed on the keywords "liver transplant" and "dermatology." Results A total of 99 liver transplant recipients were identified in this study. Sixty-nine patients (70%) had at least 1 dermatologic condition. Inflammatory skin conditions were the most common (53%), followed by cutaneous infection (36%) and benign cutaneous tumors (30%). Malignant and premalignant lesions were the least common skin conditions reported (10%). Our study results concurred with many other studies reported worldwide, demonstrating a low cutaneous malignancy burden after liver transplantation. Limitations The study included a small population size in a single center and did not have a pre-existing protocol for pretransplant dermatologic surveillance. Conclusion Although the incidence of skin cancer after liver transplant in Singapore is low, the patients will benefit from long-term dermatology surveillance, given the long-term risks of infection and malignant skin conditions.

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.To compare high-local recurrence risk features and frequency of tissue-rearranging reconstruction for head and neck KC with those for melanoma.Retrospective cohort study of KC versus melanoma treated at the Hospital of the University of Pennsylvania with Mohs micrographic surgery.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]).This was a retrospective study, and it did not compare outcomes with those of other treatment methods, such as slow Mohs or conventional excision.Melanomas of the head and neck have high-local recurrence risk features and require tissue-rearranging reconstruction more frequently than KCs do.

Background Skin cancer is the most common cancer worldwide. Objective To evaluate the burden of skin cancer in the US from 1990 to 2019. Methods Age-standardized incidence, prevalence, disability-adjusted life years (DALY), and mortality rates from skin cancer in the US were evaluated from the Global Burden of Disease 2019. Results Incidence, prevalence, DALY, and mortality rates for melanoma per 100,000 persons in 2019 were 17.0, 138, 64.8, and 2.2, respectively; for squamous cell carcinoma, rates were 262, 314, 26.6, and 0.8, respectively; and for basal cell carcinoma, rates were 525, 51.2, 0.2, and zero, respectively. Incidence and prevalence rates of melanoma and non-melanoma skin cancer (NMSC) have increased since 1990, while mortality rates have remained fairly stable. Males have had higher incidence, prevalence, DALY, and mortality rates from melanoma and NMSC every year since 1990. Incidence and prevalence of melanoma was relatively higher in the northern half of the US than in the southern half. Limitations Global Burden of Disease is derived from estimation and mathematical modeling. Conclusions Health care professionals can utilize differences and trends noted in this study to guide allocation of resources to reduce incidence and morbidity from skin cancer.

Skin cancer is the most common cancer in the UK, and incidence rates are continuing to increase. We discuss the common presentations, clinical features, examination techniques, referral guidelines, management and prognosis of both non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma) and melanoma.

Background Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. Objectives To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. Methods A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. Results Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). Limitations This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusion Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Background Few data exist to guide the application of Mohs micrographic surgery (MMS) in the pediatric population. Objective We sought to summarize the clinical characteristics of children undergoing MMS, identify challenges that limit the use of MMS in this population, and examine how these challenges can be overcome. Methods A systematic review of PubMed and EMBASE, from inception of databases to November 2, 2019, identified all cases of pediatric skin lesions treated with MMS. Results A total of 111 patients were included. The median patient age was 11 years (range 6 weeks to 17 years). The most commonly treated tumor was dermatofibrosarcoma protuberans (n = 62), followed by basal cell carcinoma (n = 30). The most common location was the head and neck (n = 34), followed by the trunk (n = 28) and the extremities (n = 23). The most commonly cited challenges in the application of MMS in children included patient cooperation, concerns for the safety of prolonged general anesthesia, availability of a MMS service in the pediatric setting, and access to a histopathology laboratory experienced in MMS sectioning. Limitations Many articles did not report specific patient characteristics. Conclusion Multiple obstacles limit the application of MMS in pediatric patients. This review describes practical methods to circumvent these obstacles to facilitate the appropriate use of MMS in children.

Background Numerous reports have described methods for repairing full-thickness upper eyelid defects using lower eyelid tissue. To avoid sacrificing the lower eyelid and thereby prevent lower eyelid sagging or dysfunction, we used innervated orbicularis oculi myocutaneous flaps harvested from the upper eyelid for upper eyelid reconstruction. Methods We modified a method reported by Moschella and Cordova for repairing full-thickness upper eyelid defects using innervated bipedicled orbicularis oculi myocutaneous flaps mobilized from the upper eyelid and labial mucosal grafts. First, we avoided the use of a Fricke flap, which is used in the original method to repair the myocutaneous flap donor site, since it can cause asymmetry of the eyebrows on both sides. Second, reconstruction of the double-fold eyelid was performed with buried sutures in the myocutaneous flap in secondary surgery, since the double eyelid fold of the original method is not necessary or is too wide for Asian people. Functional and cosmetic outcomes were assessed by six evaluators using postoperative photographs. Results Six patients with malignant upper eyelid tumours underwent repair of upper eyelid defects by our modified method. Donor sites of the myocutaneous flaps were repaired with a medial forehead flap in one patient with Merkel cell carcinoma, a lateral orbital flap in one patient with sebaceous carcinoma, and a two-stage skin graft in two patients with sebaceous carcinoma and basal cell carcinoma, respectively. The two remaining patients (one with sebaceous carcinoma and the other with basal cell carcinoma) required no donor site repair. Functional and cosmetic outcomes were good or excellent in most cases. Conclusion Our modified method for repairing full-thickness upper eyelid defects using innervated orbicularis oculi myocutaneous flaps resulted in optimal eyelid function and support, with morphologically satisfactory results including bilateral symmetry. This method provides a useful alternative to conventional methods of upper eyelid reconstruction.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but are phenotypically diverse. To improve the understanding of keratinocyte carcinogenesis, it is critical to understand epigenetic alterations, especially those that govern gene expression. We examined changes to the enhancer-associated histone acetylation mark H3K27ac by mapping matched tumor-normal pairs from 11 patients (five with BCC and six with SCC) undergoing Mohs surgery. Our analysis uncovered cancer-specific enhancers on the basis of differential H3K27ac peaks between matched tumor-normal pairs. We also uncovered biological pathways potentially altered in keratinocyte carcinoma, including enriched epidermal development and Wnt signaling pathways enriched in BCCs and enriched immune response and cell activation pathways in SCCs. We also observed enrichment of transcription factors that implicated SMAD and JDP2 in BCC pathogenesis and FOXP1 in SCC pathogenesis. On the basis of these findings, we prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Our findings highlight unique and shared epigenetic alterations in histone modifications and potential regulators for BCCs and SCCs that likely impact the divergent oncogenic pathways, paving the way for targeted drug discoveries.

There has been a drastic increase in the incidence of nonmelanoma (NMSC), including squamous, basal cell, and melanoma skin cancers worldwide. Most cases of skin cancer can be treated effectively with surgery; fewer than 10% of cases are advanced and may require additional therapies. A better understanding of the biology of skin cancer will help contribute to better prognostic information and identification of possible new therapeutic targets. Herein, the authors review the biology and pathogenesis of both NMSC and melanoma, focusing on critical cell signaling pathways mediating the disease and current therapeutic strategies targeted to underlying genetic pathways.

Basal cell carcinoma is the most common human malignancy, with an incidence exceeding all other cancers combined. Advanced basal cell cancer requires a multidisciplinary approach to management. The mainstay of treatment remains surgical excision with appropriate reconstruction. Some advanced tumors may require radical resections; however, extensive, high-risk surgery may be justified by the indolent biology of the disease and the likelihood of cure. Other options, such as radiation or systemic targeted therapy, may be considered in selected patients who either refuse or are not candidates for surgery. The focus of this article is primarily on management of these high-risk cases.

This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs) and skin cancers. It argues that field therapy rather than AK-selective therapy is the more logical approach to cancer prevention and hypothesizes that treatment early in the process of field cancerization, even prior to the appearance of AKs, may be more effective in preventing cancer as well as more beneficial for and better tolerated by at-risk individuals. Finally, the Perspective encourages use of rapidly advancing DNA analysis techniques to quantify mutational burden in sun-damaged skin and its reduction by various therapies.

Background Local recurrence rates (LRRs) after Mohs micrographic surgery (MMS) for male genital cancers have been reported in only a few small case series, and patient-reported outcomes (PROs) have not been studied. Objective To determine the LRR and PROs after MMS for male genital skin cancers. Methods Retrospective review of all male genital skin cancers removed with MMS between 2008 and 2019 at an academic center. LRR was determined by chart review and phone calls. PROs were assessed by survey. Results A total of 119 skin cancers in 108 patients were removed with MMS. Tumors were located on the penis (90/119) and scrotum (29/119). Diagnoses included squamous cell carcinoma in situ (n = 71), invasive squamous cell carcinoma (n = 32), extramammary Paget disease (n = 13), melanoma (n = 2), and basal cell carcinoma (n = 1). The LRR was 0.84% (1/119), with a mean follow-up time of 3.25 years (median, 2.36 years). The majority of survey respondents reported no changes in urinary (66%) or sexual functioning (57.5%) after surgery. Limitations Retrospective single-center experience; short follow-up time; low survey response rate; no baseline functional data. Conclusion MMS for male genital skin cancer has a low LRR and high patient-reported satisfaction with urinary and sexual function.

Radiation therapy plays an integral role in the management of cutaneous malignancies of the head and neck. This article highlights the use of radiation therapy in the definitive and adjuvant setting for basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Themes that emerge include the overall efficacy of radiation therapy as a local therapy, the relevance of cosmesis, functional outcomes, late toxicities as secondary end points, and the multitude of treatment modalities that are used.

Summary Long-term use of vismodegib is associated with treatment-emergent adverse drug reactions in clinical trials of patients with locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC). Treatment interruptions have been recommended for management of adverse drug reactions, but there is no clear guidance on the duration of those interruptions. A model-based evaluation was conducted to assess the impact of treatment interruptions on vismodegib efficacy. A tumor growth–inhibition model was developed and model-based simulations were performed to assess the proportion of patients achieving ≥30% reduction from baseline in tumor size (ie, proportion of responders) for various dosing schedules. The most conservative simulated scenario compared an intermittent dosing schedule of 12 weeks of vismodegib treatment followed by 8-week dosing interruption (repeated four times for a total duration of 80 weeks) versus 80 weeks of continuous dosing, which predicted a decrease in responders of –4.7% from 90.7% in laBCC and –3.7% from 63.0% in mBCC. These results demonstrated maintenance of vismodegib efficacy with the intermittent dosing schedule and support the recently approved recommendations of treatment interruptions of up to 8 weeks to manage tolerability in laBCC or mBCC patients in the vismodegib US prescribing information.

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Since surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence.To evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study.All consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive.Of the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P0.0001). These predictive clinical features may be helpful for decision making.

Objective Skin conditions have been associated with increased risk of Parkinson's disease (PD). Little is known about clinical and biomarker differences according to presence of skin conditions among PD patients. Studying these differences might provide insight into PD pathogenesis. Methods We examined the association between common skin conditions and risk of PD in a case-control study of 423 early drug-naive PD cases and 196 healthy controls (HC) in the Parkinson's Progression Markers Initiative (PPMI). Among PD participants, we examined if skin conditions were associated with clinical and PD-relevant biomarkers. Results Skin conditions occurred more frequently among PD participants (41%) relative to HC (32%). In multivariate analyses, we observed an association between any skin condition and PD (OR = 1.49, 95% CI = 1.03–2.16) and basal cell carcinoma and PD (OR = 2.05, 95% CI = 1.02–4.08). PD participants who reported skin conditions were older (OR = 1.68, 95% CI = 1.21–2.35) more educated (OR = 1.70, 95% CI = 0.99–2.91), had higher Semantic Fluency Test (SFT) scores (OR = 1.45, 95% CI = 1.07–1.96) and Hopkins Verbal Learning Test (HVLT) retention scores (OR = 1.55, 95% CI = 1.09–2.22) compared to PD patients without skin conditions. None of the associations remained significant after Bonferroni correction for multiple comparisons. Conclusions We observed a positive association between any skin condition as well as basal cell carcinoma and PD. PD participants with skin conditions were older, more educated, had higher SFT and HVLT retention scores compared to those without skin conditions. However, all associations were no longer significant after Bonferroni multiple comparisons correction. Observed associations should be confirmed in larger, longitudinal studies.

Background Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. Objectives To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). Methods This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. Results A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). Limitations Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusions High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.

Summary Introduction The establishment and success of new treatments are significantly influenced by patient satisfaction. Post-operative scarring is an important outcome for patients, and subsequently influences overall satisfaction with treatment. The objective was to measure post-treatment scarring satisfaction using a novel scale, the FACE-Q Skin Cancer Module, to compare electrochemotherapy (ECT) to traditional surgical excision (SE) to demonstrate equivalence of ECT and SE regarding outcome and survivorship. Methods and materials This was a multicentre first-time appraisal study of the efficacy of ECT. All patients with facial BCCs treated with either ECT or SE were deemed eligible and subsequently recruited from either a previous clinical trial or outpatient clinics, respectively. Of the 40 participants invited, 25 responses were received. Patient information recorded included age, gender, location and size of BCCs, and time since treatment. Patient outcomes were measured using the FACE-Q Skin Cancer Module. Results The ECT and SE groups consisted of 14 and 11 patients, respectively. Mean age was 68 years (M:F = 16:9), while mean time since treatment was 4.98 years (range 0.3–9.58 years). Appraisal of scars was significantly higher in the ECT cohort versus SE (p = 0.034). Cancer worry was equivalent across both cohorts (p = 0.804). According to treatment type, no correlation was detected between time since treatment and both appraisal of scars (ECT p = 0.466 and SE p = 0.214) and adverse effects (ECT p = 0.924 and SE p = 0.139). Conclusion Based on this study, ECT has superior scar outcomes and overall equivalence to SE. This demonstrates high patient satisfaction for those treated with ECT without any additional cancer worry.

Introduction Non-melanoma skin cancer (NMSC) is becoming ever more prevalent among older adults. However, older adults with NMSC are often underrepresented in clinical trials and guidelines on effective management is still unclear. The International Society of Geriatric Oncology (SIOG) created a multi-disciplinary task force to explore the potential in developing practical guidelines for the treatment of older patients with basal cell carcinoma (BCC) and skin (cutaneous) squamous cell carcinoma (cSCC). Materials and Methods A systematic literature search to identify relevant and up-to-date literature on treatment of NMSC in older adults was conducted on various databases including MEDLINE, Embase, CINAHL, Cochrane, and PubMed. The resulting papers were discussed by an expert panel, leading to a consensus recommendation. Results A total of 154 articles were identified for the expert panel to utilise in generating consensus recommendations. A major focus on geriatric assessment and management options including surgery, radiotherapy, systemic therapy, clinical monitoring, and medical/medicophysical therapy were reviewed for recommendations. Discussion Patient age should not be the sole deciding factor in the management of patients with NMSC. Assessment from a multidisciplinary team (MDT) is crucial, and the decision-making process should consider the patient's lifestyle, needs, and expectations. A comprehensive geriatric assessment should also be considered. Patients should feel empowered to advocate for themselves and have their views considered a part of the MDT discussion.

Reflectance confocal microscopy (RCM) is a noninvasive imaging tool used for in vivo visualization of the skin. It has been extensively studied for use in the evaluation of equivocal cutaneous neoplasms to decrease the number of biopsy procedures in patients with benign lesions. Furthermore, its applications are broadening to include presurgical cancer margin mapping, tumor recurrence surveillance, monitoring of ablative and noninvasive therapies, and stratification of inflammatory disorders. With the approval of category I Current Procedural Terminology reimbursement codes for RCM image acquisition and interpretation, use of this technology has been increasingly adopted by dermatologists. The first article in this 2-part continuing medical education series highlights basic terminology, principles, clinical applications, limitations, and practical considerations in the clinical use of RCM technology.

Highlights • Sertoli-Leydig cell tumors are rare sex-cord stromal tumors of the ovary. • We present a case of Sertoli-Leydig cell tumors with rhabdomyomatous differentiation on the setting of xeroderma pigmentosum. • We describe clinical, gross and microscopic examinations for diagnosis and treatment., Introduction Sertoli-Leydig cell tumors (SLCTs) are rare sex-cord stromal tumors of the ovary. Heterologous components may be present, most commonly in the intermediate differentiated and poorly differentiated groups. Because of their scarcity, SLCTs with heterologous differentiation represent a challenge in both diagnosis and management, with limited available experience. Presentation of case We report a case of a 27-year-old, Tunisian woman, followed in the Dermatology Department since the age of six months for xeroderma pigmentosum, with a history of basal cell carcinoma of the face operated on several times. The patient presented with abdominal pain and bloating associated with a medium abundance ascites on physical exam. Ultrasound showed a large left adnexal mass associated with an elevated cancer antigen 125 on serological exam. The patient underwent unilateral salpingo-oophorectomy with resection of two omental nodules. Microscopic examination concluded to poorly differentiated Sertoli-Leydig tumor with rhabdomyomatous differentiation. Adjuvant chemotherapy was performed and there was no clinical evidence of tumor recurrence during the three years of follow-up. Discussion SLCTs with rhabdomyomatous differentiation on the setting of xeroderma pigmentosum are exceptional, microscopic diagnosis and management is challenging, considering the tumor scarcity. Conclusion Further case reports and retrospective studies are required to more understand the pathogenesis of SLCTs and to determine their optimal treatment regimen.

Reconstruction of the tip of the nose following the excision of skin cancer is a cosmetic and surgical challenge. We propose using a crescentic nasojugal flap, also known as a perialar crescentic advancement flap, to repair such defects. We present a series of 13 cases in which cutaneous carcinoma (mostly basal cell carcinoma) was excised from the lateral nasal tip with clear margins and the defect repaired with a crescentic nasojugal flap. The technique was successful in all cases. None of the patients developed notable surgical complications and the postoperative outcomes were satisfactory, with no significant functional or cosmetic problems. The crescentic nasojugal flap is therefore a good option for repairing medium-sized defects on the tip of the nose.

Background Xeroderma pigmentosum (XP) is a rare genetic disease characterized by extreme photosensitivity, resulting in a higher incidence of cutaneous tumors. Reflectance confocal microscopy (RCM) is a noninvasive imaging method for diagnosing cutaneous lesions. Objective To explore the application of RCM in the follow-up of patients with XP. Methods Patients with XP underwent RCM for suspicious lesions from January 2010 through April 2019. Lesions with malignant RCM features were excised, and the results were compared with their histopathologic features. Benign lesions on RCM were monitored every 3 months. We recorded the confocal features that were related to malignancy and specifically to melanoma. Results A total of 61 suspicious lesions from 13 patients with XP were included. Thirty-three lesions (54%) were malignant (14 melanomas, 15 basal cell carcinomas, and 4 squamous cell carcinomas). Nonvisible papillae (OR, 11.8; 95% CI, 2.6-53.1; P = .001) and atypical cells at the dermoepidermal junction (OR, 11.7; 95% CI, 2.7-50.3; P = .001) were independent predictors of malignancy. Limitations There were limited numbers of patients and lesions. Most cases were retrospectively included, and some did not have a histologic analysis. Conclusions RCM is a valuable tool in the follow-up of patients with XP, reducing the need for excisions by 35%.

Introduction Dermatoses contribute to a large burden of global disease, but the relationship between socioeconomic status and the effect of dermatologic conditions in Europe is not well understood. Methods We selected Global Burden of Disease Study data sets to analyze disability-adjusted life-years (DALYs) and the annual rate of change of dermatoses between 1990 and 2017 in 43 European countries. The principal country-level economic factor used was gross domestic product per capita from the World Bank. Statistical analysis was performed with Spearman ρ correlation. Results Wealthier European countries had higher DALYs for melanoma, basal cell carcinoma, psoriasis, atopic dermatitis, acne, seborrheic dermatitis, alopecia, asthma, contact dermatitis, and viral skin disease. Poorer countries had higher DALYs of squamous cell carcinoma, urticaria, decubitus ulcers, pruritus, scabies, tuberculosis, and syphilis. Thirteen European countries were in the top 10th percentile globally for annual increase in skin and subcutaneous disease burden. Conclusion The majority of European countries have experienced an increase in skin and subcutaneous diseases in recent decades relative to the rest of the world, but the burden of individual dermatoses in Europe varies by country and socioeconomic status. DALYs can potentially serve as a purposeful measure for directing resources to improve the burden of skin disease in Europe.

The incidence of skin cancers is on the rise due to population growth and aging.1 The eyelid region is one of the common sites for skin cancers, the majority of which are basal cell carcinoma, followed by squamous cell carcinoma and sebaceous carcinoma.2 Of note, the lower eyelid is more prone to be affected by skin cancers. The eyelid is composed of anterior and posterior lamellae, and when full-thickness lower eyelid defects cannot be directly closed, reconstruction of both the posterior and anterior lamellae, along with tarsal plate replacement, are typically performed.3 However, elderly patients with skin cancer may not be amenable to such extensive surgery. Between 1997 and 2019 at our hospital, 5 patients underwent successful reconstruction of full-thickness lower eyelid defects with the repair of only the anterior lamella while allowing the posterior lamellar portion to heal secondarily. We herein report one representative case. In addition, we discuss the clinical validity of less extensive surgery for elderly patients by allowing the posterior lamellar portions of lower eyelid defects to heal secondarily.

Recent advancements in anticancer therapy have produced an array of highly specialized therapeutics that prolong disease-free survival, improve tolerability of treatment, and individualize care. With improved treatments and longer survival, treatment-related toxicities are gaining importance. Dermatologic toxicities are common, with therapy-induced secondary cutaneous malignancies of the most frequent and serious for targeted therapies, immunotherapy, and radiotherapy. Often, these eruptive malignant lesions can be treatment limiting and detrimental to quality of life. As such, dermatologists play an important role in multidisciplinary oncologic care teams for surveillance and management of secondary cutaneous malignancies. Proactive dermatologic supervision yields early diagnosis and treatment of secondary cutaneous malignancies, which limits therapy discontinuation and thus optimizes treatment through both therapeutic achievement and overall well-being.

Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters.Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field.Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration.These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.