Search Results (263)

Background/Objectives: The increasing incidence rates of keratinocyte carcinoma (KC), particularly in fair-skinned populations, call for efforts to intensify health education of the general population in addressing this prevalent skin cancer type. As a preparatory step, this systematic review summarizes the published research on the knowledge and risk perception regarding KC among individuals without medical training. Methods: The review was registered in PROSPERO (CRD42024618851) and adheres to PRISMA guidelines. The databases PubMed, Scopus, Web of Science, PsycArticles, and PsycINFO were searched on 30 July 2024. Studies were eligible if knowledge and/or risk perception was assessed in lay people. Risk of bias (ROB) was assessed with the Joanna Briggs Institute checklist for prevalence studies. Comparable outcomes (e.g., awareness of terms for KC) were meta-analyzed. Results: Included reports (n = 17) were published between 1991 and 2024 with 16,728 individuals assessed. Awareness for the most common type of KC, basal cell carcinoma (BCC), was low (20.75% of respondents (95% confidence interval (CI): 15.24–27.61)), while more respondents were familiar with colloquial terms (60.9–72.8%). Meta-analysis indicated an underestimation of the frequency of KC, with only 7.21% (CI: 4.03–12.58) identifying BCC as the most common type of skin cancer. Furthermore, concern about developing KC as assessed in only two overlapping studies was reported by only 25–30% of respondents, indicating a significant gap in risk awareness and a lack of research on risk perception regarding KC. Conclusions: This review highlights the need for targeted health education interventions to improve knowledge and preventive behaviors regarding KC. Given the limitations of the included studies, characterized by high ROB, heterogeneity of results, and a lack of standardized assessment tools, further research is essential to enhance the understanding and awareness of KC in diverse populations. Full article

Non-melanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), represents the most common type of cancer worldwide, particularly among Caucasians. While BCC is locally invasive with minimal metastatic potential, cSCC is a highly aggressive tumor with a significant potential for metastasis, particularly in elderly populations. Tumor development and progression and the metastasis of cSCC are influenced by a complex interplay between tumor cells and the tumor microenvironment. Recent research highlights the importance of various immune cell subsets, including T cells, tumor-associated macrophages (TAMs), and dendritic cells, in influencing tumor progression, immune evasion, and treatment resistance. This review outlines key regulatory mechanisms in the immune tumor microenvironment (TME) of cSCC and explores the role of cytokines, immune checkpoints, and stromal interactions. We further discuss the relevance of three-dimensional (3D) in vitro models such as spheroids, organoids, and tumor-on-chip systems as tools to mimic immune–tumor interactions with higher physiological relevance, such as macrophage activation and polarization against cSCC cells. Globally, 3D models offer new opportunities for immunotherapy screening and mechanistic studies. Understanding the immune landscape in cSCC through advanced modeling techniques holds strong clinical potential for improving diagnostic and therapeutic strategies. Full article

Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology. Full article

Background: We present an interesting case involving a tumour comprising both basal cell tumour cells and sarcomatoid tumour cells. An 86-year-old woman presented with an erythematous lesion on her left cheek. Clinical and dermoscopic findings suggested BCC. Complete excision and histopathological examination revealed a BCC with a separate proliferation of atypical spindle and epithelioid cells. Immunohistochemical staining supported the diagnosis, with basaloid cells positive for CK5/6 and Ber-EP4 and sarcomatoid cells positive for CD10 and vimentin. Results: Histology and immunohistochemistry confirmed a basal cell carcinoma with sarcomatoid differentiation. The close proximity of sarcomatoid cells to the BCC component suggests a potential role of epithelial–mesenchymal interactions in tumour development. Further investigations into the exact origin of this tumour are required. Conclusion: Basal cell carcinoma with sarcomatoid differentiation is rare. This case highlights the importance of thorough histological and immunohistochemical evaluation. Further studies are necessary to better understand the pathogenesis of such collision tumours. Full article

Skin cancers are associated with a significant psychological burden across all age groups, particularly as their global incidence continues to rise. Ultraviolet (UV) radiation—primarily UVA and UVB—remains the leading etiological factor, inducing DNA mutations in key genes such as TP53 and BRAF. Among skin cancers, basal cell carcinoma (BCC) is the most prevalent and typically indolent. In contrast, squamous cell carcinoma (SCC) tends to be more invasive, while melanoma is the most aggressive and prone to metastasis. Melanoma is especially concerning due to its rapid dissemination and its occurrence not only on the skin but also in ocular, mucosal, and nail tissues. These challenges, along with rising treatment resistance and mortality, underscore the urgent need for novel anticancer agents. Berberine—a plant-derived isoquinoline alkaloid—has attracted increasing attention for its broad-spectrum anticancer potential, including against skin cancers. In this review, we summarize current evidence regarding berberine’s mechanisms of action in melanoma and SCC, emphasizing both its preventive and therapeutic effects. We further explore its potential as an adjuvant agent in combination with conventional treatments, offering a promising avenue for enhancing the clinical outcomes of skin cancer therapy. Full article

Transient receptor potential classical or cation channels (TRPCs) are integral to tumor biology, particularly in maintaining Ca²⁺ homeostasis within cancer cells. TRPC5, a pH-sensitive member of this family, may act as a signaling molecule in the altered microenvironment of solid tumors, which are characterized by an inverted pH-gradient—with decreased extracellular and increased intracellular pH—that promotes tumor progression. This study addresses a gap in the field, as there is currently limited research on TRPC5, particularly regarding its potential role as a tumor marker. While TRPCs are known to be involved in cancer biology, the specific role of TRPC5 in solid tumors, including its potential role as a diagnostic marker, remains largely unexplored. This study is the first to examine TRPC5 expression profiles in common skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), and nevus cell nevi (NCN). Our findings reveal that the frequency of TRPC5 expression in BCC is significantly lower compared to SCC and epidermal portions of NCN and MM. These results suggest that TRPC5 could serve as an immunohistochemical marker to distinguish SCC from BCC. Additionally, this study lays the groundwork for future research into the role of TRPC5 in tumor progression and metastasis, especially since BCCs, which rarely metastasize, are predominantly negative for TRPC5. Full article

Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1–2 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1–2 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies. Full article

Background/Objectives: To evaluate the clinical and histological efficacy, safety, and cosmetic outcomes of 5% imiquimod (IMQ) cream, used in monotherapy or in combination, for periocular superficial and nodular basal cell carcinoma (BCC). Methods: A systematic search of MEDLINE, PubMed, and Google Scholar (inception—12 June 2025) identified studies reporting IMQ treatment of eyelid/periocular BCC. Randomized, nonrandomized and observational designs were eligible. Risk of bias was assessed with Cochrane RoB 2 or ROBINS-I, and certainty of evidence graded with GRADE. Results: Seven studies (n = 152 lesions) met the inclusion criteria. The pooled clinical-plus-histological clearance across case series was 82% (95% CI 72–90%). The single RCT (n = 27) reported 100% histological clearance for both IMQ and radiotherapy at 3 months, but IMQ produced superior cosmetic results. Combination immunocryosurgery (IMQ + cryotherapy) achieved 87.5% sustained remission at ≤5 years. Local adverse events—erythema, crusting, or conjunctivitis—occurred in ≥70% (85/122) of treated cases but were mild-to-moderate and self-limiting; systemic reactions were not reported. Forty-seven additional patients in a dedicated safety cohort showed only transient ocular irritation. The certainty of evidence was moderate for short-term clearance and low for long-term control because of small samples and heterogeneous follow-up. Conclusions: IMQ 5% is a useful, tissue-sparing option for selected (superficial and nodular subtypes) periocular BCCs where surgery is contraindicated or cosmesis is paramount. Overall clearance is slightly lower than Mohs surgery but comparable to radiotherapy, and cosmetic outcomes are favorable. Larger, standardized RCTs with ≥3-year follow-up are needed to confirm durability, optimize dosing schedules, and validate patient-reported outcome measures. Full article

Background/Objectives: Systemic therapy with hedgehog pathway inhibitors (HHIs) and anti-programmed cell death protein 1 (PD-1) antibodies represent the first- and second-line treatment options for advanced basal cell carcinoma (aBCC), respectively. A shift in the treatment paradigms toward the neoadjuvant approach is gaining increasing interest in aBCC management, whereby prior systemic therapy followed by surgery is likely to yield more favorable outcomes. The aim of this narrative review is to summarize the current evidence on systemic treatment options and the neoadjuvant approach for aBCC management. Methods: We performed a non-systematic review of the literature based on PubMed as search engine. Results: The pivotal phase II trials ERIVANCE and BOLT investigated the efficacy and safety profile of vismodegib and sonidegib, respectively, with reported objective response rates (ORRs) of 60.3% and 56% in laBCC patients, respectively. The pivotal phase II trial NCT03132636 investigated the efficacy and safety profile of cemiplimab in patients who progressed or were intolerant to prior HHI therapy, with an ORR of 32.1% in laBCC patients. Real-life studies confirmed the effectiveness and safety profile of HHI and anti-PD-1 immunotherapy. Several phase I/II clinical trials are currently investigating HHIs and immune-checkpoint inhibitors in the neoadjuvant setting followed by surgery for aBCC patients, with the aim of providing more favorable treatment outcomes, especially when upfront surgery would result in functional and/or aesthetic sequelae. Conclusions: Advanced BCC treatment is challenging, and the neoadjuvant approach followed by surgery is expected to reduce surgical complexity, increase tissue preservation, and improve patients’ satisfaction. Full article

Background/Objectives: Long-term outcome data of locally advanced basal cell carcinoma patients who achieve complete response (CR) on hedgehog pathway inhibitors (HHIs) are lacking, highlighting a gap in the identification of the predictors of tumor recurrence. We aimed to investigate the clinical and histological factors associated with locally advanced BCC recurrence after CR on HHIs. Patients and methods: We performed a retrospective multicenter observational study at 14 Italian tertiary referral centers (1 January 2016–1 March 2024). Univariate logistic regression was used to investigate the association between locally advanced BCC recurrence and clinical and histological features. Kaplan–Meier analysis was used to estimate relapse-free survival (RFS). Results: A total of 106 locally advanced BCC patients were enrolled, of whom 14/106 (13.2%) experienced relapse after a median follow-up of 12 months (range: 1–70 months). Low-risk locally advanced BCC histological subtypes (superficial and nodular) were associated with a decreased probability of locally advanced BCC recurrence (odds ratio [OR]: 0.15, 95% CI: 0.04–0.51; p: 0.003); a longer time to CR predicted locally advanced BCC relapse (OR: 1.07, 95% CI: 1.01–1.15; p: 0.04). Accordingly, locally advanced BCC histology and time to CR significantly impacted RFS probability. Conclusions: Specific locally advanced BCC histological subtypes and time to CR predict tumor recurrence after CR on HHIs. Full article

Background: Keratinocyte carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), presents a growing concern. Electrochemotherapy (ECT), an emerging treatment modality, combines chemotherapy and electroporation to enhance drug delivery into cells. However, reviews evaluating ECT in keratinocyte carcinomas are lacking. Objectives: This study reviews the efficacy and toxicity of ECT in the treatment and palliation of keratinocyte carcinomas. Methods: A systematic search was conducted across PubMed, Cochrane, Embase, and Scopus databases. Patient, tumor, and treatment characteristics, tumor response, long-term disease outcomes, and toxicity data were extracted. Quality of studies was assessed using validated tools. Primary endpoints included tumor response; secondary endpoints included long-term disease outcomes and toxicity. Results: Twenty-one studies were included. Complete response (CR) rates ranged from 50 to 100% and from 10 to 100% for BCC and SCC, respectively. OS rates ranged from 95 (14 months) to 100 (1 year) % and from 64 (1 year) to 85.1 (8.6 months) % for BCC and SCC, respectively. One-year local disease-free survival (LDFS) rates were 89% and 87% for BCC and SCC, respectively. For BCC, local progression-free survival (LPFS) rates were 96% (1 year), 90% (2 year), and 70% (5 year). For SCC, 1-year LPFS rates were 80% on a per-patient basis and 49% on a per-lesion basis. Conclusions: ECT is effective and tolerable in the treatment and palliation of keratinocyte carcinomas. Future studies should focus on improving reporting quality, optimizing treatment protocols, and investigating long-term outcomes. Full article

Background: Studies on somatic mutations in cancer typically report single-nucleotide variants in coding regions, while mutations in short tandem repeats (STRs) are usually overlooked. Homopolymeric regions, a subset of STRs, are stretches of DNA where only a single nucleotide is repeated multiple times (e.g., AAAAA or TTTTT). Only recently have mutations in such STR regions been seen in colorectal cancer, where microsatellite instability (MSI) is common. In non-melanoma skin cancer (NMSC), MSI is rare. In this study, we focus on somatic mutations in such homopolymeric regions in NMSC and their functional implications. Methods: We performed targeted DNA sequencing (paired tissue and blood from the same individual), using more than 400 cancer-related genes from 32 NMSC patients as cases and non-lesional skin tissue from 16 independent individuals as controls. Results: We identified NMSC-associated STR somatic mutations. These are associated with the dysregulation of DNA damage and repair mechanisms. In artificial intelligence (AI) predictive modeling, these markers could successfully differentiate basal cell carcinoma (BCC) and non-lesional skin tissue. To our knowledge, we present the first study focusing on STR somatic mutations in multiple cancer-related genes in NMSC found only in tumor tissue and not in non-lesional skin tissue. Some of them (APC, BRAF) are associated with more pronounced dysregulation of relevant gene pathways (hedgehog, Notch signaling, and Wnt signaling). Conclusions: Our findings suggest that this STR somatic mutation status might potentially be used to select BCC patients who could benefit from certain precision therapy including hedgehog inhibitors, gamma-secretase inhibitors, anti-Vasuclar endothelial growth factor (VEGF), proteasome inhibitors, and immune check-point inhibitors. Full article

Background: Basal cell carcinoma (BCC) of the ocular and periocular region is characterized by a painless progressive extension. An early diagnosis can limit the extent of facial tissue involvement and subsequent resection resulting in better cosmetic and functional results. Objectives: The aim is to provide the largest and most up-to-date overview of ocular and periocular BCCs. We also reported the first case of caruncle BCC investigated by dermoscopy and reflectance confocal microscopy (RCM). Methods: A systematic review and meta-analysis (Prospero ID CRD583032) were carried out by searching PUBMED–MEDLINE, including all articles with a full-text English version and with BCCs in eyelids, medial and lateral canthus, caruncle, conjunctiva, and orbit. The following data were collected: authors, year, title and type of publication, medical specialization, number, sex, age and comorbidities of the patients, anatomic localization of the disease, clinical and dermoscopic aspect, histological examination, and treatment. Results: We identified 731 articles through a database search, of which 236 articles matched our inclusion criteria. A total of 71.730 patients with ocular and periocular BCCs were included in the present study, and all data collected were reported in a dataset. Most of the articles included were described by ophthalmologists (67.5%), dermatologists (11.2%), or plastic surgeons (5.6%). The proportional meta-analysis revealed varying significance and heterogeneity for each type of study included. Conclusions: BCC more frequently affects the lower eyelid. The most common BCC subtype of ocular and periocular area is the nodular form. Limited data are available concerning the application of dermoscopy and RCM in this area. RCM may be particularly useful for early diagnosis, mapping, and treatment monitoring of ocular and periocular BCCs. Surgery still remains the first-choice treatment. Full article

Background/Objectives: High-dose-rate (HDR) interventional radiotherapy (IRT) represents a valuable treatment alternative for basal cell carcinoma (BCC) of the midface, especially in the presence of esthetic or functional issues related to surgery. This retrospective study examines the clinical outcomes of patients who underwent HDR-IRT at our institution. Methods: Patients (pts) with histologically confirmed midface BCC were treated with HDR-IRT using superficial, interstitial, or endocavitary implants depending on tumor characteristics. Fractionation regimens were tailored to tumor location: 45 Gy in 9 fractions twice a day (the cheeks/lips) and 44 Gy in 14 fractions (the nose, with the first and last fractions delivering 4 Gy each, administered once daily, and the remaining 12 fractions delivering 3 Gy each, administered twice daily (BID) with an inter-fraction interval of at least 6 h). Treatment efficacy was assessed based on local control rates, toxicity (CTCAE criteria), and cosmetic outcomes. Results: Eight patients were considered. The most common tumor site was the nose (seven patients, 87.5%), followed by the upper lip. Tumors were either primary (three patients, 37.5%) or residual/recurrent after previous surgery with involved margins (five patients, 62.5%). The median follow-up was 6 months (range: 1–19 months). Clinical local control was achieved in all cases, with persistent alteration at dermoscopy in one patient six months after the completion of treatment. Acute toxicities were minimal, with two patients developing grade 3 skin toxicity, which resolved within 1–3 months with topical management. Cosmetic outcomes were favorable across all patients. Conclusions: HDR-IRT is a well-tolerated, effective, and cosmetically favorable treatment for midface BCC. Our institutional experience supports its use as an alternative to surgery in cosmetically sensitive areas and in selected patients/lesions unfit for surgery. Endocavitary implants appear to be an effective option to cover the full thickness nasal wall without resorting to interstitial implants. Full article

Gorlin-Goltz syndrome (GGS) is also known as Nevoid basal cell carcinoma syndrome (NBCCS). In the most common manifestation, GGS is diagnosed based on multiple cysts in the jaw bones, namely OKCs (odontogenic keratocysts). Other features might include major and minor clinical and radiological criteria to confirm this syndrome. Quite commonly, BCCs (basal cell carcinomas), bifid ribs, palmar and plantar pits, and ectopic calcification of the falx cerebri can be found in the majority of patients. Currently, the mutation of the PTCH1 gene seems to be responsible for GGS occurrence, while the male-to-female ratio is 1:1. The following radiological study based on OPGs and CBCT confirmed multiple cystic lesions in jaw bones, confirmed to be OKCs in the histopathological evaluation with an occurrence of numerous skin BCC lesions. In cases of most oral OKC cystic lesions, either surgical removal, curettage, or enucleation with or without any bone grafting can be used with a good amount of success. Rarely, some stable bone osteosynthesis procedures have to be carried out to avoid pathological bone fractures after cyst removal. A special consideration should include the temporomandibular joint. TMJ surgery and the replacement of the joint with an alloplastic material can be performed to improve biting, chewing, proper mouth opening, and maintain good patient occlusion. The authors want to present how effective and simple a standard dental panoramic radiograph combined with CBCT is and how it is suitable for GGS detection. They also want to underline how a standard TMJ prosthesis can be used as an alternative to a custom-made prosthesis. Full article