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BACKGROUND: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. METHODS: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. RESULTS: During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. CONCLUSION: The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and thiazides (RR = 1.10, 95% CI = 1.04-1.16); for squamous cell carcinoma with calcium channel blockers (RR = 1.08, 95% CI = 1.01-1.14), diuretics (RR = 1.29, 95% CI = 1.17-1.43), and thiazides (RR = 1.36, 95% CI = 1.15-1.61); and for melanoma in angiotensin-converting enzyme inhibitors (RR = 1.09, 95% CI = 1.03-1.14), calcium channel blockers (RR = 1.08, 95% CI = 1.03-1.12), and thiazides (RR = 1.09, 95% CI = 1.02-1.17). The quality of evidence was low or very low. We observed evidence for dose-response for thiazides with basal cell carcinoma; angiotensin-converting enzyme inhibitors, diuretics, and thiazides with squamous cell carcinoma; and angiotensin-converting enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.

Background/Objectives: Cidofovir, an antiviral drug approved for cytomegalovirus retinitis, has emerged as an alternative treatment option for virally induced cutaneous and mucocutaneous conditions, as well as being trialed as a treatment for select neoplasms. In this review, we highlight the existing evidence, clinical uses, and rationale of using cidofovir for the treatment of cutaneous pathologies. Methods: A PubMed database literature search was conducted to identify relevant articles for inclusion in this review. Results: Cidofovir has several cutaneous applications in various formulations including intravenous, topical, and subcutaneous administrations. Primarily through case reports, case series, and retrospective reviews, cidofovir has demonstrated efficacy in treating a variety of virally induced conditions-verruca vulgaris, herpes simplex virus, molluscum contagiosum-as well as in adjuvant treatment for select neoplasms. The drug has shown efficacy in immunocompromised and immunocompetent adults and children alike. Conclusions: The body of literature supports the use of cidofovir as an effective and well-tolerated treatment for many viral cutaneous pathologies, and encourages further study for its use as an adjuvant therapy for neoplastic disease.

Background Objectives Methods Results Conclusions Basal cell carcinomas (BCCs) are the most common cancers worldwide. Although most BCCs are amenable to local treatment, there are limited therapeutic options for surgically unresectable locally advanced and metastatic BCCs. Activation of the sonic hedgehog signalling pathway plays a significant role in the development of most BCCs. Hedgehog pathway inhibitors (HPIs) can be used to inhibit this pathway. Efficacy and safety data on HPI use in Australia is scarce.This study aims to present the effectiveness and safety of HPI at a tertiary dermatology referral centre.We conducted a retrospective analysis of the clinical charts of all patients with BCC treated with an HPI at a tertiary Dermatology referral centre in New South Wales, Australia from 1 January 2016 to 1 July 2023.Twenty‐three patients with BCCs were treated with an HPI; 11 locally advanced, 8 multiple, 3 basal cell naevus syndrome and 1 metastatic. All patients were of Caucasian background, with a median age of 56. Across 41 treatment cycles, the median treatment duration was 4 months. The overall response rate (ORR) was 20/23 (87%) and complete response (CR) rate was 9/23 (39%); patients treated with sonidegib achieved an ORR of 11/12 (92%) and CR of 4/12 (33%), and vismodegib‐treated patients achieved an ORR of 9/11 (82%) and CR of 5/11 (45%). Patients who responded to HPI treatment also responded to a subsequent HPI rechallenge. Common treatment emergent adverse events (TEAEs) included muscle spasms, dysgeusia and alopecia. Dysgeusia was more frequent with vismodegib than sonidegib (p = 0.0001). There was no evidence to suggest a difference in other TEAEs between the two HPIs. Four treatment cycles were stopped due to grade 3 muscle spasm.In our cohort of 23 patients being treated with HPI, the ORR was 87% and CR was 39%. All patients who experienced TEAEs and had a drug holiday successfully responded to HPI rechallenge. TEAEs, particularly muscle spasms, are common reasons for treatment cessation. Clinicians should implement strategies to mitigate TEAE to improve drug survivability. [ABSTRACT FROM AUTHOR]

ABSTRACT 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]

It has long been widely acknowledged that ultraviolet (UV) light is an environment risk factor that can lead to cancer, particularly skin cancer. However, it is worth noting that UV radiation holds potential for cancer treatment as a relatively high-energy electromagnetic wave. With the help of nanomaterials, the role of UV radiation has caught increasing attention in cancer treatment. In this review, we briefly summarized types of UV-induced cancers, including malignant melanoma, squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma. Importantly, we discussed the primary mechanisms underlying UV carcinogenesis, including mutations by DNA damage, immunosuppression, inflammation and epigenetic alterations. Historically limited by its shallow penetration depth, the introduction of nanomaterials has dramatically transformed the utilization of UV light in cancer treatment. The direct effect of UV light itself generally leads to the suppression of cancer cell growth and the initiation of apoptosis and ferroptosis. It can also be utilized to activate photosensitizers for reactive oxygen species (ROS) production, sensitize radiotherapy and achieve controlled drug release. Finally, we comprehensively weigh the significant risks and limitations associated with the therapeutic use of UV radiation. And the contradictory effect of UV exposure in promoting and inhibiting tumor has been discussed. This review provides clues for potential clinical therapy as well as future study directions in the UV radiation field. The precise delivery and control of UV light or nanomaterials and the wavelength as well as dose effects of UV light are needed for a thorough understanding of UV radiation. [ABSTRACT FROM AUTHOR]

The ocular surface and orbit constitute unique microenvironments in the human body. Current advances in molecular research have deepened our understanding of tumor development in these regions. Tumors exhibit greater heterogeneity compared to normal tissues, as revealed by pathological and histological examinations. The tumor microenvironment (TME) plays a crucial role in the proliferation and progression of cancer cells. Factors from the external environment or the body's own inflammation and microcirculation interact within the TME, maintaining a delicate balance. Disruption of this balance, through uncontrolled signal pathway activation, can transform normal or benign tissues into malignant ones. In recent years, various systemic immunotherapies have been developed for cancer treatment. This study reviews the epidemiology of ocular surface and orbital tumors include squamous cell carcinoma, basal cell carcinoma, sebaceous carcinoma and lymphoma in conjunction with their occurrence, growth, and underlying mechanisms. We propose that by examining clinical histopathological images, we can identify specific and shared microscopic features of tumors. By collecting, classifying, and analyzing data from these clinical histopathological images, we can pinpoint independent diagnostic factors characteristic of tumors. We hope this study provides a basis for future exploration of the mechanisms underlying different ocular diseases. [ABSTRACT FROM AUTHOR]

Esophageal dysphagia is most commonly caused by motility disorders and intrinsic mechanical obstruction. However, extrinsic obstruction, such as pericardial effusion, is rare causes of dysphagia. We present an 89-year-old male with history of Waldenstrom macroglobulinemia, Charcot-Marie-Tooth syndrome, and basal cell carcinoma presenting with generalized weakness, productive cough, shortness of breath, and dysphagia to both solids and liquids. A chest X-ray obtained showed cardiomegaly with suggested central vascular congestion and pulmonary edema. Further imaging with computed tomography (CT) abdomen and pelvis showed a moderate-to-large pericardial effusion. Patient later developed signs and symptoms of cardiac tamponade, requiring urgent pericardiocentesis with removal of 1 L of sanguineous fluid. Up to today, only 6 cases of dysphagia due to pericardial effusion have been described. This case displays another rare case and highlights the importance of recognizing dysphagia as a critical symptom as well as non-gastrointestinal (GI) causes of dysphagia. [ABSTRACT FROM AUTHOR]

Background: Identifying modifiable risk factors is essential for the prevention of skin cancer; however, establishing causality can be challenging in conventional epidemiological studies. This study aimed to determine the causal associations of potentially modifiable risk factors with skin cancer using Mendelian randomization (MR). Methods: Genetic instruments for 53 risk factors, including socioeconomic status, dietary and lifestyle factors, anthropometric measures, medication use, and comorbidities, were identified from previous genome-wide association studies. Two-sample MR analyses were performed using summary statistics for three major types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Findings were verified using multiple MR methods under different assumptions and replication datasets. Results: Genetic liability to sunburn occasions, actinic keratosis, and prior skin cancers was associated with a higher risk of all three types of skin cancer, whereas genetic liability to vitiligo was associated with a lower risk. For specific skin cancer types, genetically predicted higher nevus counts and occupational class were associated with an increased risk of melanoma. Genetic liability to rheumatoid arthritis, type 2 diabetes, and increased physical activity were associated with a lower risk of BCC. Genetically predicated body mass index showed a negative association with BCC, and a positive association with SCC. Conclusions: Our study reaffirmed several previously established risk factors and identified novel potential risk factors for skin cancer. Further work is needed to unravel the biological pathways in different skin cancer types and translate our findings to inform public health policies. [ABSTRACT FROM AUTHOR]

Background: Basal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis. Objective: This study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy. Methods: A total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants. Results: Dermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker. Conclusions: The lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques. [ABSTRACT FROM AUTHOR]

Nevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by a diverse clinical presentation, which includes developmental abnormalities and tumorigenesis that can impact multiple organ systems. Basal cell carcinoma is the most common and characteristic clinical presentation in patients with NBCCS. There are three identified causative genes for this disease, the PTCH1 gene located at 9q22-31, the PTCH2 gene at 1p32-34, and the SUFU gene at 10q24.32. In this paper, we report a case of multiple nevoid basal cell carcinoma. The mutated gene in this patient was determined to be the ELP1 gene located on chromosome 9. This patient's ELP1 gene mutation may contribute to the development of multiple nevoid basal cell carcinomas on the face. [ABSTRACT FROM AUTHOR]

Aim Basal cell carcinoma (BCC) is one of the most common malignant non-melanoma carcinomas and is an important health problem for all countries. There are many studies on the effect of human lipoprotein metabolism and high-density lipoprotein (HDL-C) function on skin cells, but there are no detailed clinical studies on BCC yet. In addition, higher phospholipid and cholesterol content was found in cancerous and precancerous lesions of the skin compared to normal tissue. The aim of our study was to evaluate the lipid profile in patients with BCC and to try to find any relationship between BCC and molecules that have an important place in HDL-C functionality. Methods The patient group consisted of 39 patients who were clinically diagnosed with BCC by biopsy in hospital clinics. The control group (n:44) was randomly selected from patients of the same age group without a diagnosis of BCC who applied to different clinics of the same hospital. Routine lipid level, Apolipoprotein A1 (Apo-A1) level and Paraoxonase (PON-1) enzyme measurements were made from serum samples taken from the patients and control groups participating in the study. Results The most important findings of this study, a statistically significant decrease in serum Apo-A1 level and a decrease trend in PON-1 enzyme can be considered in BCC patients compared to control groups. Conclusion Lipid metabolism and HDL functionality, may play a role in the development of BCC. [ABSTRACT FROM AUTHOR]

Objective: We sought to examine possible differences in BCC characteristics and treatment patterns between two matched cohorts of Hispanic White and non-Hispanic White individuals. Methods: In this single institution, retrospective matched cohort study, data from patients with biopsy proven BCC from June 2005 to May 2022 was collected. Demographic, BCC, and treatment characteristics were compared between Hispanic White and non-Hispanic White individuals using a Wilcoxon rank-sum test, for continuous and ordinal variables, and Fisher's exact test, for categorical variables. Results: A total of 604 individuals with a diagnosis of biopsy-proven BCC were matched in a 1:1 fashion by age (± 0 years) and sex, based on self-identified ethnicity as Hispanic or non-Hispanic. Since all patients self-identified as White race, the two cohorts were labeled Hispanic White (n=302) and non-Hispanic White (n=302). The most frequent location for BCC was in the H area, 129 [42.7%] White Hispanic group vs 132 [43.7%] White non-Hispanic group (p = 0.87). In both Hispanic White and non-Hispanic White groups, the predominant subtype of BCC was the nodular (149 [50.2%] vs 164 [54.7%], p = 0.25). The median BCC pre-operative size in the Hispanic White group was 0.9 cm, whereas in the non-Hispanic White group, it was 1.0 cm (p = 0.004). Furthermore, the MMS defect size in the Hispanic White group had a median of 1.3 cm, while in the non-Hispanic White group, it was 1.6 cm (p < 0.001). Limitations: Retrospective design, single-center study, and self-reported race and ethnicity. Conclusion: Both groups had similar demographics, tumor features, treatments, and post-operative complications. Notably, preoperative lesion and MMS defect sizes were larger in non-Hispanic Whites than in Hispanic Whites, contrary to expectations. Despite assumptions of poorer skin cancer outcomes among Hispanics, our findings indicate increased sizes in non-Hispanic Whites. Given the diversity in genetics and clinical traits within ethnicities, especially Hispanics, more research is needed for precise insights into disease outcomes across diverse backgrounds. [ABSTRACT FROM AUTHOR]

Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most frequent of all cancers, with an increasing incidence. The first line therapy is surgical excision, but topical therapies can be used in low-risk superficial BCCs, while the more advanced, unresectable, or metastatic BCCs benefit from systemic therapies with hedgehog inhibitors and immunotherapy. The purpose of this review is to highlight local and systemic immunotherapies and their efficacy in the management of BCCs. Local therapies can be considered in superficial and low-risk nodular BCCs, with imiquimod frequently used for its antitumor and immunoregulatory properties. Imiquimod alone demonstrated higher histological clearance rates, but patients treated with imiquimod experienced more adverse events than ones treated with other therapies. Imiquimod can be used as an adjuvant before Mohs micrographic surgery and can also be combined with other local therapies, like curettage, electrodesiccation, cryosurgery, and photodynamic therapy, with some treatment methods yielding results comparable with the surgery. Interferons and Interleukin-2 were evaluated in a small number of studies with different results. Systemic immunotherapies with programmed death-ligand 1 (PD-L1) inhibitors showed inconsistent results in patients with advanced BCCs, being effective in some patients that progressed on or were intolerant to hedgehog pathway inhibitors (HHI). [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancer (NMSC) is primarily categorized into basal cell carcinoma (BCC), the most prevalent form of skin cancer, and cutaneous squamous cell carcinoma (cSCC), the second most common type. Both BCC and cSCC represent a significant health burden, particularly in immunocompromised individuals and the elderly. The immune system plays a pivotal role in the development and progression of NMSC, making it a critical focus for therapeutic interventions. This review highlights key immunological targets in BCC and cSCC, with a focus on immune checkpoint molecules such as PD-1/PD-L1 and CTLA-4, which regulate T cell activity and contribute to immune evasion. This review also highlights anti-tumor immune cell subsets within the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TILs) and dendritic cells. Additionally, it examines the immunosuppressive elements of the TME, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs), as well as their roles in NMSC progression and resistance to therapy. Emerging strategies targeting these immune elements, such as monoclonal antibodies, are also discussed for their potential to enhance anti-tumor immune responses and improve clinical outcomes. By elucidating the immunological landscape of BCC and cSCC and drawing comparisons to melanoma, this review highlights the transformative potential of immunotherapy in treating these malignancies. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8+ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8+ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8+) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8+ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancer is a major global problem, and over the last decade, ultrasound technology has advanced significantly, enhancing our ability to detect and identify the most common types of skin cancer, including both the primary tumor and its locoregional metastases. Background: Skin cancer is the most common cancer in human beings. Ultrasound is a powerful and non-invasive imaging technique that has expanded its use in dermatology, including in the skin cancer field. The full range of critical anatomical information provided by ultrasound cannot be deduced from a naked eye examination, palpation, or other imaging techniques such as dermoscopy, confocal microscopy, magnetic resonance imaging, or PET-CT (Positron Emission Tomography-Computed Tomography). Methods: This review practically analyzes the main ultrasonographic features of the most common types of skin cancers and the performance of the locoregional staging according to the literature, which is illustrated by state-of-the-art clinical and ultrasonographic correlations. Results: The most common types of skin cancer show recognizable ultrasonographic patterns. Conclusions: Among the current radiological imaging techniques, ultrasound has the highest axial spatial resolution. Compared to other imaging techniques used in dermatology, it shows the great advantage of penetrating the soft tissues thoroughly, which allows us to detect and identify the most common skin types of skin cancer, including both the primary tumor and its locoregional metastases. [ABSTRACT FROM AUTHOR]

Objective. The primary aims of the study were to (1) explore the association of skin cancer and four ultraviolet radiation (UVR) indicators (sunbed use, healthcare data on diagnosed melanocytic nevi (MN) and actinic keratosis (AK), and latitude of birthplace), and (2) find factors other than UVR that could explain the increasing trend in incidence of skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and cutaneous malignant melanoma (CMM). Methods. This population‐based cohort study used self‐reported questionnaire data from the Stockholm Public Health Cohort, encompassing 103 questions, merged with data from Swedish national registers. The study population included almost 35,000 Swedish‐born people aged 30–66 years in 2014. Binomial logistic regression was employed for analysis. A forward stepwise regression was applied to select significant risk factors among all the factors included. We tentatively tested >30 variables separately for any relationship with each of the three skin cancers. A 5% level of significance was applied. Melanoma in situ and SCC in situ were excluded. Results. The four UVR‐related factors (sunbed use, being diagnosed with AK or MN, birthplace latitude) had a significant association with at least one of the three skin cancers that remained after adjustment including behavioural, social, hereditary, and medical factors. Sunbed use >10 times before age 30 years was related to all three skin cancers; SCC adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.12–2.47, CMM (aOR 1.57, 95% CI 1.11–2.22), and the clearest dose‐response association with BCC (aOR 1.74, 95% CI 1.46–2.06). None of the examined lifestyle factors, except physical activity, had any significant associations with UVR indicators or skin cancer. Conclusion. We did not find any preventable explanatory cause other than UVR exposure for the increasing incidence of skin cancers. This result remained when adjusting for an array of possible confounders including behavioural, social, hereditary, and medical factors. [ABSTRACT FROM AUTHOR]

Mohs micrographic surgery (MMS) is the gold standard for removing basal cell carcinomas (BCCs) due to its ability to guarantee 100% margin evaluation through frozen section histopathology, offering the highest cure rate among current treatments. However, noninvasive imaging technologies have emerged as promising alternatives to clinical assessment for defining presurgical margins. This systematic scoping review examines the efficacy of these imaging modalities, focusing on those approved for clinical use by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A systematic search of EMBASE, Scopus, PubMed, and the Cochrane Public Library databases identified 11 relevant studies out of 2123 records, encompassing 644 lesions across five imaging techniques. The findings suggest that dermoscopy, high‐frequency ultrasound (HFUS), optical coherence tomography (OCT), line‐field optical coherence tomography (LC‐OCT), and reflectance confocal microscopy (RCM) show potential in detecting BCC margins, which could enhance MMS by providing better preoperative planning, informing patients of expected defect size, aiding in reconstruction decisions, and reducing overall procedure costs. This review discusses the benefits and limitations of each technique, offering insights into how these innovations could influence the future of BCC management. Emerging imaging techniques could enhance MMS by improving BCC margin assessment and reducing costs. Their adoption will depend on price and ease of use. [ABSTRACT FROM AUTHOR]

To examine population-level scrotal cancer incidence rates and trends among adult men in the United States. Data from the United States Cancer Statistics, covering approximately 96% of the United States population, were analyzed to calculate age-standardized incidence rates of scrotal cancer among men aged 18 years and older from 1999 to 2020. Trends in incidence rates were evaluated by age, race and ethnicity, Census region, and histology using joinpoint regression. Overall, 4669 men were diagnosed with scrotal cancer (0.20 per 100,000). Incidence rates were highest among men aged 70 years and older (0.82 per 100,000). Rates were higher among non-Hispanic Asian or Pacific Islander men (0.31 per 100,000) compared to other race and ethnicity groups. The most common histologic subtypes were squamous cell carcinoma (35.9%), extramammary Paget disease (20.8%), and sarcoma (20.5%). Incidence rates decreased by 2.9% per year from 1999 to 2019 for non-Hispanic Asian or Pacific Islander men, decreased by 8.1% per year from 1999 to 2006 for basal cell carcinomas, and increased by 1.8% per year from 1999 to 2019 for extramammary Paget disease; otherwise, rates remained stable for all other variables examined. While scrotal cancer incidence rates were higher than previously reported, rates were still low and stable over time. [ABSTRACT FROM AUTHOR]

Background. Sebaceous carcinoma in situ outside the ocular region is an exceedingly uncommon. It is an intraepidermal neoplasm originating from sebaceous glands limited to the epidermis with no invasion into the underlying dermis or beyond. Although sebaceous carcinoma in situ is predominantly observed in ocular regions, particularly the eyelids, instances of its occurrence in extraocular locations are infrequent, with only a limited number of examples reported in the literature. Case Presentation. A 63-year-old man presented with a left posterior arm lesion. Microscopic examination revealed a proliferation of poorly differentiated atypical neoplastic sebocytes confined to the epidermis with pleomorphic nuclei, prominent nucleoli, and clear cell changes. The neoplastic cells demonstrated positive staining for adipophilin, androgen receptor, epithelial membrane antigen, P63, BerEP4, and keratin 7. Microsatellite instability markers showed preserved nuclear staining for MLH1, PMS2, MSH2, and MSH6. A definitive diagnosis of sebaceous carcinoma in situ was rendered. Discussion. The distinctive histopathologic characteristics typically involve the presence of atypical sebaceous cells confined within the epidermis. Atypical cells often exhibit enlarged nuclei, increased mitotic activity, and prominent nucleoli. A panel of epithelial membrane antigen, adipophilin, and androgen receptors is essential for ensuring an accurate diagnosis. Conclusion. This report underscores the importance of considering sebaceous carcinoma in situ in diagnosis in atypical locations, emphasizing the need for a comprehensive histopathologic examination and immunohistochemical staining panel. This article aims to demonstrate the rarity of sebaceous carcinoma in situ in extraocular sites to broaden our understanding of its diverse clinical presentations. [ABSTRACT FROM AUTHOR]

Background Basal cell carcinoma (BCC) is the most frequent malignancy reported in populations with fair skin. In most countries, BCCs are only partially or not at all recorded, and incidence data are lacking. Objectives This study assessed the current incidence rates and trends in the only two French départements where BCCs have been recorded for several decades. Methods This regional population-based study thus used data from two French cancer registries (Doubs and Haut-Rhin) where first-time BCC diagnoses were recorded. The European age-standardized incidence rates (EASR) were calculated per 100 000 person-years (PY). The trends and the annual percentages of change were assessed using joinpoint analysis. Results In all, 48 989 patients were diagnosed with a first BCC in the study period. The median age at diagnosis was 69 years and the BCCs were mainly located on the head and neck (68.8%). In the Doubs area between 1980 and 2016, the EASR of BCC increased from 59.9 to 183.1 per 100 000 PY. The annual increase for men was 5.73% before 1999 and 1.49% thereafter, and among women 4.56% before 2001 and 1.31% thereafter. In the Haut-Rhin area, the EASR increased from 139.2 in 1991 to 182.8 per 100 000 PY in 2019. Among men, the EASR increased annually by 2.31% before 2000, and by 0.29% after 2000; among women, it increased by 0.95% over the entire period (1991–2019). In the most recent period and for these two départements, the age-specific incidence rates of BCC for men and women were close before the age of 60 years, except for the 40–49-year age group, where the rates were significantly higher among women. For patients aged 60 years and over, men had much higher rates of BCC. Conclusions BCC incidence has increased since 1980 and is still rising, particularly among men and the elderly. A slowing was observed from 2000, which could be explained by a shift in the management of BCCs and by the possible efficacy of prevention actions. This study provides insight into the BCC burden in France and highlights the need to maintain effective prevention strategies, as incidence is still increasing. [ABSTRACT FROM AUTHOR]

Traditionally, for patients who are poor candidates for surgery and/or radiotherapy, palliative chemotherapy is often offered but with significant toxic side effects. However, recent advancements in our understanding of tumor biology and molecular genetics have brought new understanding to the molecular pathways of certain tumors and cancers. This has ushered in a new era of precision medicine specific to a tumor or cancer treatment pathway (targeted therapy) or directed to host-tumor responses (immunotherapy). This article will focus on recent updates in the application of available targeted and immunotherapy for managing orbital and periorbital tumors and tumor-like conditions, which include cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, cutaneous melanoma, Merkel cell carcinoma, sebaceous gland carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, orbital meningioma, neurofibromatosis, Langerhans cell histiocytosis, ocular adnexal lymphoma, orbital lymphatic malformation, and adenoid cystic carcinoma. [ABSTRACT FROM AUTHOR]

Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger’s kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06–0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity. [ABSTRACT FROM AUTHOR]

The phenomenon of surface plasmon resonance (SPR) has attracted a lot of attention in recent years due to its potential applications in various fields, including biology, chemistry, materials physics and sensing technologies. In particular, SPR is used in optical devices, sensors and optoelectronic devices because of its sensitive and selective sensing capabilities. In this paper, we have used a numerical approach based on the finite element method (FEM) to study the performance of a highly sensitive D-shaped optical fiber biosensor, exploiting SPR, for the early detection of cancer in individual living cells. The sensitive part of the proposed biosensor consists of a thin layer of gold (Au) covered by a layer of titanium dioxide TiO2. Our numerical analysis aims to find the optimum design and handling parameters for detecting three types of cancer, namely breast cancer MDA-MB-231, MCF-7 and skin cancer (basal cells). To achieve this goal, we modeled the sensor's sensitivity to the change in refractive index of the surrounding biological medium when introduced into healthy human cells and their cancerous counterparts. Our results show that the maximum sensitivity of the proposed sensor reaches the values of 2017 n m. R I U - 1 , 2016 n m. R I U - 1 and 1571 n m. R I U - 1 respectively when used for the detection of MDA-MB-231, MCF-7 and Basal cell cancers. RI resolution is estimated at 4 , 96. 10 - 6 R I U for MDA-MB-231 and MCF-7, while for Basal cell it is estimated at 6 , 37. 10 - 6 R I U . [ABSTRACT FROM AUTHOR]

Post-oncological nasal reconstruction presents both aesthetic and functional challenges. While established methods exist for quantitatively evaluating functional results following surgery, equivalent systems for assessing aesthetic outcomes are lacking. Three-dimensional (3D) photogrammetry, already used in maxillofacial and orthodontic surgery for aesthetic evaluation, overcomes some limitations of traditional methods like direct anthropometry. However, its applicability in oncological facial reconstruction has not yet been explored. In our study, we applied the 3dMDtrio™ system for the quantitative analysis of line and surface modifications following nasal reconstruction. We conducted a prospective observational study enrolling patients with skin neoplasms located on the nose undergoing surgical excision and reconstruction. Using the 3dMDtrio™ system, we measured the dimensions and projections of nasal surfaces and the positions of specific landmarks before and after surgery. The surface measurements were then correlated with aesthetic evaluations performed by three plastic surgeons, not involved in the procedure, using a 5-point Likert scale. We included 33 patients with a mean age of 71 years, ranging from 40 to 94. We obtained complete documentation of all postoperative measurements for 21 patients. We observed significant changes in the positions of the landmarks post-surgery, limited to the right ala and nasion. The average nasal surface area was 4674.41 mm2 ± 477.24 mm2 before surgery and 4667.95 mm2 ± 474.12 mm2 after surgery, with no significant discrepancies. The evaluation using the Likert scale revealed an average score of 3.04 ± 0.48, with a significant negative correlation to the measured surface changes. Our findings suggest that 3D photogrammetry can be considered a valid method for objectively assessing volumetric changes associated with post-oncological nasal reconstructive surgery. [ABSTRACT FROM AUTHOR]

Guidelines on clinical margins for basal cell carcinoma (BCC) excisions were recently published, yet the ambiguity regarding the margin continues for surgeons and pathologists. The purpose of this study was to determine the incomplete excision rate of BCC, determine the factors associated with incomplete excision, and evaluate the completeness of reporting between surgeon and pathologist. A single-center retrospective analysis was conducted on pathology reports from single excisions of BCC specimens between January 1, 2019 to December 31, 2020. The primary outcome was the incomplete excision rate (positive margins) as reported by pathologist. Logistic regression was used to determine the relationship between incomplete excision rate and anatomical location, pathologist, and surgeon. The completeness of surgeon pathology requisition forms was evaluated qualitatively. Seven hundred and fifty-six pathology reports were included. The incomplete excision rate was 12% (n = 94). The most common site of incomplete excision was head and neck (n = 87, 15%), followed by trunk (n = 5, 7%), and extremities (n = 2, 2%). Five hundred and seventy-nine specimens from 6 surgeons and 9 pathologists were included in the logistic regression analysis. The Wald test showed that the location was significantly associated with incomplete excision (p < 0.05), whereas surgeon and pathologist reports were not (p > 0.05). Regarding missing information, only 47 (6%) pathology reports included "excision" in the requisition form. Four hundred and three (53%) specimens had no clinical history. The incomplete excision rate found in this study falls within the report range in the literature. Neither surgeon nor pathologist had significant association with incomplete excision. Incomplete excision rate of BCC may be inflated owing to the lack of standardization in requisition form and pathology reporting. [ABSTRACT FROM AUTHOR]

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Double primary malignancy though uncommon, we often encounter in our clinical practice. The lung malignancy is known to cause left vocal cord paralysis. Bilateral abductor paralysis secondary to adenocarcinoma of the lung with concurrent basal cell carcinoma of the face is not common. Proper counseling and timely management are needed in these cases of multiple primary malignancies. Early evaluation in all cases of hoarseness can help in early diagnosis and management. [ABSTRACT FROM AUTHOR]

Backrgound: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations. Methods: Based on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed. Results: Three cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity. Conclusions: This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma. [ABSTRACT FROM AUTHOR]

Introduction: Basal cell carcinoma (BCC) is a common skin cancer that rarely metastasizes but can deeply infiltrate local tissues. The small number of unresectable BCC cases makes it difficult to conduct clinical trials, resulting in delays in the development of effective drugs for BCC. Cancer gene panel testing has led to an increasing number of new treatment proposals for patients with solid tumors for whom no standard treatment is available. Case Presentation: We described a case of unresectable BRCA1 L63*-mutated BCC invading the parietal bone, which was successfully treated with cisplatin and fluorouracil. Conclusion: Our present case suggests that comprehensive mutation analysis by gene panel testing is important in advanced BCC because genes other than those involved in the hedgehog signaling pathway can be driver genes. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most frequent malignant tumour worldwide and incidences are rising rapidly. BCC grow locally, but can invade surrounding tissues. Little is known concerning their impact on the health-related quality of life (HrQoL), and limited available data reports contradicting results. Measuring HrQoL in BCC patients should be done using disease-specific questionnaires such as the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire. The aim of this study was to assess the BCC-related HrQoL by examining all relevant patient, tumour and treatment characteristics to identify the main factors for the BCC-related impact. Specific attention for older BCC patients wass brought forward because of the often complex decisions in this subgroup. Patients ≥ 18 years with a history of BCC were asked to fill in the BaSQoL questionnaire, consisting of 5 subdomains. Multivariable analyses were done using a generalized additive model (GAM) because of the need for incorporation of non-linear functions. The study obtained approval of the Ethics Committee of the Ghent University Hospital (EC/2019/1352). Informed consent was obtained from all subjects. All experiments were performed in accordance with relevant guidelines and regulations. Four hundred patients with a median age of 66 were enrolled. Mean BaSQoL subscores were 0.78 (SD 0.63) for 'behaviour', 1.01 (SD 0.73) for 'diagnosis&treatment', 0.90 (SD 0.73) for 'worries', 0.40 (SD 0.63) for 'appearance' and 1.20 (SD 0.75) for 'other people', illustrating the low to moderate impact of BCC on the HrQoL. A GAM with subsequent ANOVA testing was done for all relevant variables. In 4 out of 5 BaSQoL subdomains 'age' showed a significant correlation ('behaviour' p = 0.007; 'diagnosis&treatment' p = 0.026; 'worries' p = 0.003; 'appearance' p = 0.008). Lower BaSQoL scores were seen in older patients, meaning less BCC-impact on their HrQoL. There was a clear non-linear correlation between BaSQoL scores and age, illustrating that the impact of BCC on the HrQoL shows a rapid decrease starting around the age of 70. This study is the first to illustrate the relation between the BCC-related HrQoL and the age of patients with the use of a disease-specific HrQoL instrument. We found a lower BaSQoL score in older adults, with a specific age group of interest starting around the age of 70–75. This is an argument for a potential wait-and-see strategy for BCC in these patients. [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 Design Results Conclusions Squamous cell carcinoma (SCC) of presumed lung origin (PLO) is now the second most frequent histologic subtype of non‐small cell carcinoma after adenocarcinoma. The use of clinic‐genomic correlation provided by comprehensive genomic profiling (CGP) can revise clinicopathologic diagnoses of presumed primary lung SCC (PLO‐SCC) to diagnoses of metastatic SCC of cutaneous origin (C‐SCC).A total of 10 146 samples of clinically advanced PLO‐SCC (84% known Stage IV) passed QC metrics and were designated as PLO‐SCCs by review of test requisition forms, clinical notes, and pathology reports. One thousand seven hundred sixty‐one cases of known primary C‐SCC were also included in this study. All samples underwent hybrid capture‐based CGP (Foundation Medicine, Inc.) using a targeted gene panel to evaluate all classes of genomic alterations (GA), determine MSI, TMB, and genomic ancestry status. The mutational signature (MS) of each case was called by the decomposition method using reference signatures in the COSMIC database. PD‐L1 tumor cell expression was determined by IHC (22C3; Dako). All results were compared using the Fisher exact method with the false discovery rate corrected with a Benjamini–Hochberg adjustment.A total of 253 of 10 146 (2.5%) PLO‐SCC cases featured a UV+ MS; 812 of 1761 C‐SCC (46.1%) that also featured a UV radiation exposure MS (UV+) were also included in this study. PLO‐SCC UV+ cases used for sequencing included tissue samples from the lung (162), lymph node (34), soft tissue (33), liver (8), head and neck (7), brain (5), and skin thought to be metastatic sites from primary lung SCC (4). The PLO‐SCC UV+ patients were 78.7% male and had a median age of 72 years, which was younger and more frequently male gender than both the C‐SCC UV+ and C‐SCC UV− patients (p < 0.0001). Both the PLO‐SCC UV+ and C‐SCC UV+ featured greater GA per tumor than the PLO‐SCC UV− cases (p < 0.0001). In the PLO‐SCC UV− cases, tobacco exposure and APOBEC were the most frequent MSs. For the biomarkers associated with immune checkpoint inhibitor efficacy, when compared with the PLO‐SCC UV− cases, the PLO‐SCC UV+ cases featured more cases with TMB ≥10 mutations/Mb (88.5% vs. 36.5%; p < 0.0001) and ≥20 mutations/Mb (66.8% vs. 6.8%; p < 0.0001) and a trend for less frequent positive PD‐L1 (≥50% TPS) IHC staining (30.2% vs. 39.6%; p = 0.062). Compared to PLO‐SCC UV− cases, PLO‐SCC UV+ and C‐SCC UV+ cases were more likely to harbor clinically‐actionable GA in PTCH1 and NOTCH1/2 (p < 0.0001) and less likely to harbor clinically‐actionable GA in KRAS, PIK3CA, and PTEN (p < 0.0001). The frequency of PTCH1 GA in PLO‐SCC UV+ (32% vs. 0.9% in PLO‐SCC UV−) suggested that PLO‐SCC UV+ may include a mixture of C‐SCC and cutaneous basal cell carcinomas (C‐BCC) with squamous differentiation.When cases of PLO‐SCC undergo CGP, a small 2.5% subset of cases that featured a UV MS emerge that indicates that these tumors may actually represent metastatic cutaneous SCC or BCC with squamous differentiation. Given the significant treatment and clinical impact associated with the resolution of the true diagnosis of these cases, the use of genomic sequencing in PLO‐SCC may be clinically beneficial. [ABSTRACT FROM AUTHOR]

Background: Basal cell carcinoma is the most prevalent skin cancer, most characterized by local aggressiveness but with low metastatic potential, and bone metastasis is quite heterogeneous, thus the incidence profile is variable size from 0.0028% to 0.5%. We have this patient with an unusual example of basal cell carcinoma with bone metastases to add to the scarce report on this matter. Case description: Here we document a 48-year-old Persian man with a background of being exposed to the sun for a long time. He was diagnosed with an ulcer on the cheek, which was clinically characterized and further confirmed by biopsy as morpheaform basal cell carcinoma. Following the first round of excision, multiple relapses eventually metastasized to the bone. The latter was found on follow-up radiologic scans. This case is characterized by the aggressive nature of the disease and the heterogeneity of basal cell carcinoma growth, thus challenging the conventional view of basal cell carcinoma behavior. Treatment included surgical excision of the primary lesion, which was treated with radiotherapy afterward. However, the skeleton improved slowly during follow-up, and palliative care was eventually pursued to control symptoms and improve quality of life. Conclusions: This was a rare case of basal cell carcinoma metastasis to non-bone organs, which reminded us to consider basal cell carcinoma metastasis, especially in the case of atypical basal cell carcinoma. Therefore, risk-aware patient management is essential. Moreover, these findings highlight the role of further research into the mechanisms of basal cell carcinoma metastasis, leading to improved therapeutic strategies that may lead to potential improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions One of the hereditary syndromes associated with multiple early‐onset basal cell carcinomas (BCCs) is basal cell nevus syndrome (BCNS), of which a minority is caused by germline SUFU mutations. Germline SUFU mutations show a spectrum of phenotypes, of which multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is one. Patients with MHIBCC develop multiple basaloid skin tumors from middle age onwards.Three patients presenting with an MHIBCC phenotype were tested for a germline SUFU mutation. Skin biopsies were assessed by two dermatopathologists.Our study adds three new pathogenic SUFU variants, including a mosaic, to the current literature. Literature suggests a spectrum of phenotypes of patients carrying the same SUFU mutation, which ranges from the MHIBCC phenotype, to BCNS, to patients that develop life‐threatening brain tumors. This last risk is significantly higher in germline SUFU mutation carriers when compared to BCNS patients carrying germline PTCH1 mutations.Germline SUFU mutation carriers should be recognized as a distinct group of patients carrying specific health risks, independent of meeting the BCNS criteria. Phenotypic prediction based on the specific SUFU mutation seems unfeasible. It is of utmost importance that the less apparent MHIBCC phenotype is recognized, to provide (second generation) germline SUFU mutation carriers appropriate healthcare. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions BRCA1‐associaed protein‐1 (BAP1) inactivated tumours (BIMT) are rare melanocytic tumours that may be mistaken for Spitz tumours or melanoma. They occur sporadically or in association with the BAP1 tumour predisposition syndrome (BAP1–TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. The aim of this study was to characterise the clinicopathological features and the immunohistochemical expression pattern of preferentially expressed antigen in melanoma (PRAME) of BIMT in a large patient cohort.Ethical approval was obtained, haematoxylin and eosin‐stained slides were reviewed, PRAME immunohistochemistry was performed and clinical follow‐up was obtained from patient records. Sixty‐five BIMT from 38 patients (F:M = 4.4:1) were identified. BIMT were typically located on the trunk and head and neck (median size = 0.5 cm). Seven patients with BAP1–TPDS (range = 16–66 years, median = 25) had multiple BIMT (median = 5), while sporadic BIMT were solitary (median patient age = 39 years). One of seven patients with BAP1–TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive without recurrence of BIMT (median follow‐up = 42 months). BIMT presented as intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity and moderate to severe cytological atypia in 63% of cases. A background conventional naevus was present in 64%. PRAME immunohistochemistry showed negative or weakly patchy positive staining in all BIMT.BIMT are more common in a sporadic setting and behave indolently, despite worrying cytological atypia. PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma. [ABSTRACT FROM AUTHOR]

A cutaneous carcinosarcoma (cCS) is a rare and aggressive skin cancer characterized by both carcinomatous (epithelial) and sarcomatous (mesenchymal) components, making it a biphasic tumor. Despite its occurrence in various organs, a cCS is exceptionally rare in the skin, predominantly affecting older males. The etiology of a cCS is unclear, but it may originate from a single progenitor cell capable of dual differentiation or from a collision of carcinoma and sarcoma cells. Clinically, a cCS presents as a rapidly growing, painful, ulcerated nodule or plaque on sun-exposed skin, with a high risk of local invasion and metastasis. Histopathologically, a cCS includes various epithelial components, such as squamous cell carcinoma and basal cell carcinoma, along with undifferentiated sarcomatous components resembling atypical fibroxanthoma. The tumor may also exhibit heterologous differentiation like angiosarcomatous or rhabdomyosarcomatous features. We present three cases of a cCS, highlighting their clinical and histological characteristics and comparing them with previously reported cases. Understanding a cCS is complicated by its rarity and diverse presentation, emphasizing the need for further research to elucidate its pathogenesis and optimal management. [ABSTRACT FROM AUTHOR]

Restoring the integrity of the external nose presents a complex surgical challenge due to its three-dimensional structure and subunit divisions. The most frequent causes of nasal defects include basal or squamous cell carcinoma, animal bites and trauma. The reconstruction approach varies depending on factors such as the defect's size, the affected subunit of the nose, the condition and quality of the surrounding tissues and the surgeon's expertise. Commonly employed surgical techniques for nasal reconstruction include the forehead flap, nasolabial flap, Rieger flap, bilobed flap, and free autologous skin graft. We present a clinical case of a patient with a full-thickness nasal alar defect who underwent three-layer reconstruction with a combination of an inverted skin flap- for the internal lining, a conchal graft to substitute the missing alar cartilage and a forehead flap for external coverage. One of the challenges of nasal reconstruction surgery is to restore a full-thickness defect, especially the internal nasal lining. We offer a different perspective on this problem, showcasing considerable advantages, as there are limited literature data on this method. [ABSTRACT FROM AUTHOR]

Background. Basal cell carcinomas (BCCs) are common human malignancies with a rising incidence in recent years. While BCCs have a low mortality rate, they are often associated with significant local skin damage characterized by erythema, skin ulceration, and persistent pigmentation. Surgery, radiotherapy, and systemic chemotherapy have traditionally been the principal treatments for these skin injuries. However, electrochemotherapy has recently been proposed as a novel local treatment with promising results for various skin cancers, including BCC, while avoiding the side effects of conventional therapies. ECT involves a local electrical stimulus that enhances cell membrane permeability, thereby enabling the targeted intracellular accumulation of the chemotherapeutic agent. Case Report: We report a case of a 68-year-old man with an ulcerated BCC, following his progress up to 14 months post-ECT treatment, with positive outcomes. Discussion and Conclusions: We achieved a complete clinical response and noted an improvement in the patient's quality of life. This technique is fast, repeatable, requires minimal hospitalization, and reduces healthcare costs and adverse effects compared to major surgery. Therefore, it can be considered an alternative or complementary approach to traditional surgery for treating BCC of the head and neck. [ABSTRACT FROM AUTHOR]

Background Basal cell carcinoma (BCC) is the most common type of nonmelanoma skin cancer. Typically, resection requires a safety margin of ≥4 mm. When removing tumor cells, achieving complete excision with minimal safety margins and reconstructing the defect to preserve the original appearance are important. In this study, we used a 3-mm resection margin to confirm recurrence and re-resection rates. Methods Electronic medical records and photographic data were obtained for patients with primary BCC lesions less than 2 cm in diameter who underwent wide excision with a 3-mm surgical margin from January 2015 to November 2021. We analyzed factors determining recurrence and re-resection rates, such as tumor size, location, age, sex, underlying diseases (including immunosuppression state), ethnicity, subtypes, tumor borders, etc. Results This study included 205 patients. The mean age and follow-up period were 73.0 ± 11.5 years and 10.2 ± 8.0 months, respectively. The recurrence and re-resection rates were 1.95% and 25.85%, respectively. A statistically significant correlation was found between recurrence rate and tumor border (p = 0.013) and the re-resection rate was correlated statistically with location (p = 0.022) and immunosuppressed patients (p = 0.006). Conclusion We found that a 3-mm excision margin provided sufficient safety in small facial BCC, resulting in ease of surgery and better aesthetic outcomes. However, surgical margins must be determined case by case by integrating various patient factors. In particular, a surgical margin of ≥4 mm is required for BCC in high-risk areas, immunosuppressed patients, or poorly defined border. [ABSTRACT FROM AUTHOR]

Skin cancer is a widespread worldwide health concern, manifesting in many subtypes such as squamous cell carcinoma, basal cell carcinoma, and melanoma. Although all these types occur frequently, they generally lack the possibility of being cured, emphasizing the importance of early discovery and treatment. This comprehensive study explores the role of programmed cell death protein 1 (PD‐1) in skin cancer, focusing on its molecular mechanisms in immune regulation and its critical role in tumor immune evasion, while also clarifying the complexities of immune checkpoints in cancer pathogenesis. It critically evaluates the clinical applications of PD‐1 inhibitors, spotlighting their therapeutic potential in treating skin cancer, while also addressing the significant challenge of resistance. This work further discusses the evolution of resistance mechanisms against PD‐1 inhibitors and suggests potential approaches to mitigate these issues, thereby enhancing the effectiveness of these therapies. The study further highlights the current state of PD‐1 targeted therapies and sets the stage for future research aimed at optimizing these treatments for better clinical outcomes in skin cancer. [ABSTRACT FROM AUTHOR]

Skin cancer is a significant public health issue, making accurate and early diagnosis crucial. This study proposes a novel and efficient hybrid deep‐learning model for accurate skin cancer diagnosis. The model first employs DeepLabV3+ for precise segmentation of skin lesions in dermoscopic images. Feature extraction is then carried out using three pretrained models: MobileNetV2, EfficientNetB0, and DenseNet201 to ensure balanced performance and robust feature learning. These extracted features are then concatenated, and the ReliefF algorithm is employed to select the most relevant features. Finally, obtained features are classified into eight categories: actinic keratosis, basal cell carcinoma, benign keratosis, dermatofibroma, melanoma, melanocytic nevus, squamous cell carcinoma, and vascular lesion using the kNN algorithm. The proposed model achieves an F1 score of 93.49% and an accuracy of 94.42% on the ISIC‐2019 dataset, surpassing the best individual model, EfficientNetB0, by 1.20%. Furthermore, the evaluation of the PH2 dataset yielded an F1 score of 94.43% and an accuracy of 94.44%, confirming its generalizability. These findings signify the potential of the proposed model as an expedient, accurate, and valuable tool for early skin cancer detection. They also indicate combining different CNN models achieves superior results over the results obtained from individual models. [ABSTRACT FROM AUTHOR]

Background: Arsenical keratosis is a precancerous dermatosis which could be induced by long‐term exposure to arsenic poisoning. Arsenic is often added to traditional Chinese medicine in a non‐compliant manner to increase the effectiveness of psoriasis treatment, which is often the main cause of arsenic poisoning in Chinese patients with psoriasis. Objectives: We performed a systemic review of arsenic keratosis during the past 32 years to better understand the sources, treatment, and prognosis of arsenic keratosis in China. Methods: We searched Medline/PubMed, Embase, CNKI, and Wanfang databases for research studies published between 1992 and 2024. A total of 64 papers with 78 individual Chinese of arsenical keratosis were included in this analysis. Results: Of the patients included in the analysis, 92.21% of arsenic poisoning was due to iatrogenic factors: Chinese traditional medicine. Seventy‐six patients (98.70%) had skin manifestation of hyperkeratotic papules and plaques, 68 patients (88.31%) had hyperpigmentation, 43 cases (55.84%) had hypopigmentation, and only 4 had a clear indication of Mees' lines in nails. A total of 52.63% of patients presented with tumors, including squamous cell carcinoma, Bowen's disease, and basal cell carcinoma. For patients with tumors, 20 opted for surgery, 6 for radiotherapy, and 3 for PDT. All patients with only cutaneous tumors are currently well‐controlled. Death occurred in one patient with metastatic squamous cell carcinoma. Keratinizing papules improved significantly in 70.59% of patients treated with Acitretin Capsules. Conclusions: In this study, arsenic sources in Chinese patients were mainly from traditional Chinese medicine, and there were no reports of exposure to water sources or occupational sources in the past 32 years. Most of the patients showed keratinizing papules and pigmentation, and more than 1/2 of the patients showed skin tumors, mainly squamous cell carcinoma. The treatments of tumors are mainly surgical treatment, PDT and radiotherapy can also be selected. The improvement in keratinizing rash was greater than 70% with acitretin capsules. Patients with this disease should be regularly followed up for early detection and timely treatment of potential malignant tumors. [ABSTRACT FROM AUTHOR]

Giant basal cell carcinomas (GBCCs) are rare neoplastic lesions with an incidence less than 0,5% and destructive capabilities higher than their precursors. Mushroom-like growth of cutaneous tumors described in 1806. by Albert, is still a rare phenomenon. GBCC’s with mushroom-like macroscopic characteristics were hardly reported. We present a mushroom-like GBCC, treated successfully with wide surgical excision. An 85-year-old male with a progressively growing skin lesion was admitted to our clinic. He came seeking medical care with a bleeding painful skin lesion. The tumor developed from a small papule into an exophytic pedunculated lesion with a fetid, ulcerated, exudative surface. Physical examination revealed 7x5x1.5cm mushroom-like, exophytic, pedunculated mass with rolled borders and partial cutaneous necrosis, signs of secondary infection and bleeding. The lesion was surgically removed. Histopathology showed basal carcinoma cell (BCC). Two months post-operatively there was no signs of tumor recurrence and secondary metastases without a need for additional treatment. GBCCs can still be identified in the 21st century. It arises due to neglecting of the lesion, inconspicuous localization usually covered by clothing. Mushroom-like morphology is rare in BCCs. Treatment is usually surgical excision, with a high success rate and an improvement in quality of life. [ABSTRACT FROM AUTHOR]

Skin cancer is a disorder marked by inappropriate skin cell proliferation, which is frequently brought on by UV radiation exposure from tanning booths or the sun. It can present as melanoma, squamous cell carcinoma, or basal cell carcinoma, with varying levels of malignancy and available therapies. Our newly developed photonic crystal fiber (PCF) has exceptional efficacy in the identification of skin cancer. The proposed US model has a heptagonal core and a clad surface with a heptagonal pattern. The PCF analyzer that has just been released shows a maximum relative sensitivity (RS) of 95.35% as well 94.29% for the basal (cancer) alongside basal (normal), respectively. For the aforementioned cells, we also looked at the confinement loss (CL) of 1.74 × 10–14 dB/m, 5.98 × 10–13 dB/m, plus the effective material loss (EML) of 0.0077 cm−1, 0.0088 cm−1. Rapid identification in skin cancer allows for improved results, tailored treatment, and prompt intervention. Early detection of cancer makes milder medications available, which lessens the need for aggressive treatment. Moreover, increasing the treatment of patients and simplifying the continual sickness monitoring process. Accurate evaluation also helps with research into developments that enhance global recognition as well as treatment options. The new PCF, with its exceptional detecting capacity, may have been instrumental in the prompt discovery of such harmful organisms. In summary, there are a lot of opportunities in the medical field. [ABSTRACT FROM AUTHOR]

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome. [ABSTRACT FROM AUTHOR]

Background: Oncological anxiety associated with biological therapy is a particular challenge in inflammatory bowel disease (IBD), and it has raised questions about the need for the dermatological assessment of the skin before starting biological therapy. Methods: The aim of this study was to assess the frequency of dermal lesions, including cutaneous malignancies, in IBD patients. This retrospective, single-center study evaluated 805 IBD patients who qualified for biological treatment and were subjected to a dermatological assessment. Results: Dermal lesions (DLs) were found in 15.5% (125) of IBD patients. A risk factor for DLs was higher with body mass index (OR = 1.08, 95% CI [1.02; 1.14], p = 0.007). Surprisingly, there was no effect of thiopurines between the groups with and without DLs (90.4% vs. 84.6%, MD = 0.06, 95% CI [0.01; 0.12], p = 0.118). Moreover, cutaneous malignancies were diagnosed in 9 cases (1.1%), including 4 basal cell carcinomas, 4 squamous cell carcinomas, and 1 melanoma skin cancer. Only 13.4% of patients complied with our strict policy of skin surveillance every 6–8 months. Conclusions: DLs, including cutaneous malignancies, are common in patients with IBD, making skin monitoring at the initiation of biological treatment an extremely useful tool. The lack of effect of the drugs used suggests that skin surveillance is necessary in all IBD patients. The low compliance of skin monitoring among immunosuppressed patients indicates the need for better education on the prevention of cutaneous malignancies. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is a firmly established tool in oncology and is gaining importance in dermato-oncology. However, its use in advanced basal cell carcinoma (BCC) is limited, with only a few case reports and a single study focused on vismodegib. This study evaluates the role of 18F-FDG PET/CT in advanced BCC treated with sonidegib. Methods: We retrospectively assessed the clinical data of patients with advanced BCC who underwent 18F-FDG PET/CT between January 2022 and January 2024. Inclusion criteria included histologically confirmed BCC, FDG-avid lesions on baseline PET/CT, and a minimum follow-up of 6 months. Metabolic response was assessed using the PET Response Criteria in Solid Tumors (PERCIST). Results: Four patients with advanced BCC treated with sonidegib were included, presenting with a total of 10 hypermetabolic lesions at baseline PET/CT. The mean interval between baseline and follow-up scans was 8.7 ± 1.6 months. According to PERCIST, two patients achieved a complete metabolic response (CMR), while the other two had stable metabolic disease (SMD). Low baseline-standardized uptake values (i.e., SUVmax, SUVmean) and reduced total lesion glycolysis (TLG) were associated with CMR. No relapses were observed during follow-up. Conclusions: This study suggests that 18F-FDG PET/CT may help identify advanced BCC patients who are likely to benefit from sonidegib treatment. Further research is needed to fully explore the potential of PET/CT in this specific clinical context. [ABSTRACT FROM AUTHOR]