Search Results (723)

Background: Reflectance confocal microscopy (RCM) enables noninvasive, high-resolution visualization of skin tumors and may improve preoperative margin assessment in nonmelanoma skin cancer (NMSC). However, its impact on surgical outcomes in routine clinical practice remains incompletely defined. Objective: To evaluate surgical outcomes of NMSC managed with systematic preoperative RCM-guided margin assessment, comparing wide local excision (WLE) and Mohs micrographic surgery (MMS). Methods: We conducted a retrospective study of 71 consecutive NMSC treated at a tertiary dermatologic oncology center. All tumors underwent RCM evaluation for diagnosis and preoperative margin mapping. Outcomes included positive margins after WLE, local recurrence, recurrence-free survival, and the number of Mohs stages. Associations were analyzed using Fisher’s exact tests and Firth penalized logistic regression. Results: Among 47 tumors treated with WLE, positive margins occurred in 10.6%. Among 24 MMS cases, 70.8% were cleared in a single stage. Local recurrence occurred in 14.9% of WLE-treated tumors and in none of the MMS-treated tumors (p = 0.087). All recurrences occurred in tumors initially demonstrated positive margins after WLE, despite subsequent re-excision and histologic clearance. In multivariable Firth regression, MMS was associated with a lower risk of recurrence (OR 0.13; 95% CI, 0.008–2.10). Conclusions: In this RCM-guided cohort, low margin positivity after WLE and high single-stage clearance in MMS suggest improved surgical accuracy and efficiency. Recurrence was confined to margin-positive tumors, supporting a margin-driven model of tumor control and highlighting RCM as a potential preoperative margin-control strategy. Full article

Mohs micrographic surgery (MMS) is a highly specialized skin cancer procedure that combines complete microscopic margin assessment with maximal preservation of uninvolved tissue. The technique is based on staged excision of the tumor with systematic horizontal sectioning and real-time examination of the entire peripheral and deep surgical margins, allowing further tissue removal only in areas where residual tumor is identified. Its unique strength lies in the ability to detect subclinical tumor extensions that may be missed by conventional excision and standard vertical sectioning, thereby improving local control while minimizing unnecessary tissue sacrifice. Since its introduction in the 1930s by Frederic E. Mohs, the technique has evolved into a cornerstone of modern dermato-oncology, particularly for tumors arising in anatomically critical areas, recurrent neoplasms, and histologically aggressive malignancies. MMS is now widely regarded as the treatment of choice for high-risk basal cell carcinoma and cutaneous squamous cell carcinoma because of its superior cure rates and tissue-sparing approach. Beyond its oncologic advantages, MMS allows precise clinicopathologic correlation and immediate reconstruction tailored to the final defect, contributing to favorable functional and cosmetic outcomes. As experience with the technique has expanded, so too has interest in adjunctive tools for preoperative tumor delineation and margin control, further refining patient selection and surgical accuracy. Overall, MMS represents an essential advance over conventional excision for selected cutaneous malignancies, offering an optimal balance between radical tumor clearance and preservation of normal tissue. Full article

Background/Objectives: The early identification of skin cancer by standard RGB dermoscopy is a clinical difficulty because of the complex visual differences between impacted lesions and healthy tissue. Methods: For the biomedical challenge, a novel approach to signal processing and image reconstruction is introduced in this study, called the spectrum-aided visual enhancer (SAVE). The proposed SAVE mechanism aims at reconstructing the diagnostically relevant spectral information from the conventional RGB dermoscopic images using the principles of hyperspectral imaging (HSI) and band selection (BS). After quality control and pre-processing, the images in the ISIC2019 dataset were selected, with 865 images that contain basal cell carcinoma (BCC), seborrheic keratosis (SK), and actinic keratosis (AK) lesions. To reduce data leakage, the dataset was split into training, validation, and testing subsets of 70%, 20%, and 10%, respectively. Five supervised deep learning object detection models were trained and tested on the conventional RGB image dataset and on the SAVE-enhanced dataset. Five supervised deep learning object detection models, namely, YOLOv8, YOLOv10, YOLOv11, SSDLite, and SSD, were trained and tested on the conventional RGB image dataset and the SAVE-enhanced dataset. Additional repeated experimental assessments and statistical comparisons were also carried out to evaluate the improvement in performance. Results: The experimental results showed that the SAVE-based pre-processing always yielded better performance in terms of lesion detection than conventional RGB image processing. The SAVE framework for SSD was evaluated and compared with all other evaluated models and was found to be the most successful, with an accuracy of 96%, a precision of 97%, a recall of 96%, and an F1 score of 96%. Conclusions: The results indicate that the proposed SAVE framework could be a promising RGB-compatible spectral enhancement technique for boosting skin cancer detection and computer-aided dermatologic analysis with the aid of AI. Full article

Transient receptor potential vanilloid 5 (TRPV5) is a calcium- and pH-sensitive ion channel. It plays a role in tumor biology and cellular calcium homeostasis. Due to the inverse pH gradient in solid tumors (extracellular acidosis and increased intracellular pH), TRPV5 is interesting as a signaling molecule in tumors, as the altered pH in the tumor microenvironment (TME) impacts tumor growth and metastasis. This is the first study to analyze the expression of TRPV5 in common skin cancers, i.e., basal cell carcinomas (BCC), squamous cell carcinomas (SCC), malignant melanomas (MM) and melanocytic nevi (MCN). The results showed a significantly lower expression of TRPV5 in BCC than in all other tumor entities analyzed. While less than half of the BCC were positive for TRPV5, SCC, MM, and MCN exhibited a high level of positive staining results. These results suggest that TRPV5 may especially help as a novel marker in the differentiation of SCC from BCC. The low expression of TRPV5 in BCC, a rarely metastatic tumor, may also point to a role of TRPV5 in the progression of epithelial skin tumors. Further functional studies, however, are needed to clarify the exact role of TRPV5 in skin tumors. Full article

The glycosidic composition of Psolus phantapus was studied for the first time. Two new glycosides, phantapusosides A (1) and B (2), and the known psolusoside P (3) were isolated and their structures were established by analysis of ¹H, ¹³C NMR, 1D TOCSY, and 2D NMR (¹H,¹H COSY, HMBC, HSQC, ROESY), and HR-ESI mass spectra. These compounds are structurally close to those isolated from other representatives of the genus Psolus: P. fabricii, P. peronii and P. chitonoides. These data confirm the chemotaxonomic significance of triterpene glycosides of sea cucumbers, demonstrating that closely related species biosynthesize structurally similar metabolites. The cytotoxic activity of compounds 1 and 2 was studied against four human breast cancer cell lines (MCF-7, T-47D, MDA-MB-231, MDA-MB-468), as well as the non-tumorigenic mammary epithelial cell line MCF-10A and the pancreatic epithelioid carcinoma cell line PANC-1. The glycosides were selectively active against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Notably, both glycosides inhibited the clonogenic potential of TNBC cell lines more significantly than their metabolic activity (MTT assay) and demonstrated a more pronounced colony-inhibiting effect toward the basal-like cell line MDA-MB-468, making this cell line a promising model for future investigation of the antitumor effects of glycosides. Full article

Nicotinamide (NAM), the amide form of vitamin B3, has gained increasing attention in dermatology due to its potential role in both skin aging and non-melanoma skin cancer (NMSC) prevention. This review summarizes the biological rationale and current clinical evidence supporting the use of NAM and other NAD⁺ precursors in photoaging and cutaneous carcinogenesis. Chronic ultraviolet exposure induces DNA damage, oxidative stress, inflammation, immune dysregulation, and extracellular matrix remodeling, linking photoaged skin to increased susceptibility to actinic keratoses (AKs), squamous cell carcinoma (SCCs), and basal cell carcinoma (BCCs). Through the NAD⁺ salvage pathway, NAM contributes to the maintenance of intracellular NAD⁺ pools, thereby influencing energy metabolism, DNA repair, mitochondrial function, redox homeostasis, and the activity of NAD⁺-dependent enzymes. Preclinical studies indicate that NAM enhances DNA repair, reduces oxidative stress and inflammatory signaling, supports autophagy and mitophagy, and improves epidermal barrier function and extracellular matrix integrity. Clinically, the strongest evidence for anti-aging effects concerns topical NAM, which consistently improves wrinkles, texture irregularities, pigmentation, and barrier function. Oral NAM has demonstrated chemopreventive activity in high-risk patients with previous NMSC, particularly by reducing the incidence of new SCCs and AKs during active treatment. However, despite a strong mechanistic rationale, current evidence remains heterogeneous, and additional long-term, skin-focused clinical trials are needed to better define efficacy, safety, optimal dosing strategies, and patient selection. Full article

Background: Non-melanoma skin cancers (NMSCs) of the head and neck represent a therapeutic challenge due to the region’s complex anatomy, functional considerations, and frequent involvement of high-risk anatomical zones. Local recurrence remains a clinically significant concern, however real-world data regarding recurrence patterns and associated risk factors in facial NMSCs are limited. Objectives: To evaluate the incidence of local recurrence of facial skin cancers after surgical treatment and to determine clinicopathological and anatomical actors associated with an increased risk of recurrence. Methods: In this single-center retrospective cohort study, consecutive patients undergoing surgical excision of facial NMSC were included. The treatment of choice was always surgical excision under general or local anesthesia, with an adequate margin of macroscopically unchanged tissue. Mohs surgery was not used, and none of the patients received immunosuppression. Clinical and pathological data were extracted from medical records. Histopathological examination constituted the basis for establishing the final clinical diagnosis and thus was not verified otherwise. The primary outcome was histologically confirmed local recurrence defined as the reappearance of a tumor of the same histopathological type at the same anatomical site as the previously excised lesion. Patients in the non-recurrence group were defined as those who did not experience any recurrence within a 5-year follow-up period after the initial surgical treatment. Fisher’s exact test and the Mann–Whitney U test were used for statistical analysis. Logistic regression was performed to explore factors associated with recurrence. Due to incomplete follow-up data for the non-recurrent group, we limited the timing analysis to recurrent cases only, as these limitations precluded the use of standard survival analysis. Results: A total of 302 lesions were analyzed, with recurrence status available for 291 tumors. The overall recurrence rate was 28.52%. Basal cell carcinoma (BCC) was the most common histopathological subtype. Recurrences occurred more frequently in anatomically high-risk areas, particularly the scalp, temple and nose. Infiltrative BCC subtypes demonstrated higher recurrence rates than nodular and superficial subtypes. Patients with recurrent tumors were younger than those without recurrence. A history of prior skin radiotherapy was associated with increased odds of recurrence. Tumor size and surgical margin width were not significantly associated with recurrence. Multivariate models showed limited discriminatory ability, suggesting that additional unmeasured factors contribute to recurrence risk. Conclusions: Local recurrence of non-melanoma skin cancers in the head and neck region remains a substantial clinical concern, particularly in high-risk anatomical sites and tumors with aggressive histopathological features. These findings highlight the importance of long-term follow-up and support further prospective studies to improve recurrence risk assessment and treatment strategies. Full article

Background/Objective: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, arising from epidermal basal cells or the outer root sheath of the pilosebaceous unit. Despite its generally indolent clinical behavior, BCC exhibits substantial histopathological heterogeneity, which may reflect underlying biological differences among its subtypes. This study aimed to evaluate the expression of Wnt/β-catenin pathway components and tumor-associated markers—including COX-2, Ki-67, tryptase, CD1a, and WNT3A—across different histopathological subtypes of BCC. Methods: This retrospective cross-sectional study included 100 formalin-fixed paraffin-embedded (FFPE) BCC specimens retrieved between January 2006 and September 2015. After the exclusion of three cases due to inadequate tissue quality, the tumors were classified into nodular (n = 60), infiltrative (n = 16), superficial (n = 9), and other subtypes (n = 12). The immunohistochemical expressions of COX-2, Ki-67, CD1a, intratumoral and peritumoral tryptase, β-catenin, and WNT3A were assessed and compared among the BCC subtypes. Results: No significant differences were observed among the BCC subtypes regarding age or sex distribution. The expression levels of COX-2, Ki-67, CD1a, and mast cell-associated markers (intratumoral and peritumoral tryptase) did not differ significantly among the groups (all p > 0.05). Conversely, β-catenin expression was significantly higher in the infiltrative subtype compared with the other histological variants (p = 0.001). WNT3A immunoexpression was uniformly negative across all evaluated cases. Conclusions: Most of the evaluated immunohistochemical markers did not differentiate among the BCC subtypes. However, the significantly increased β-catenin expression observed in the infiltrative subtype suggests a potential association with tumor growth patterns rather than serving as a specific discriminative marker, thereby highlighting the biological heterogeneity of BCC. Although WNT3A expression was uniformly negative in all cases, this finding should be interpreted cautiously and does not allow for definitive conclusions regarding its role in Wnt pathway activation. Overall, these results support the need for further investigation into the Wnt/β-catenin pathway heterogeneity in BCC. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy. Full article

Background/Objectives: Trichoblastoma is a benign follicular adnexal tumor that typically arises on the head and neck. Large variants at atypical locations pose considerable diagnostic challenges because their clinical presentation can be indistinguishable from malignant soft tissue neoplasms. Herein, we describe a case of trichoblastoma presenting as a large subcutaneous thigh mass that was correctly diagnosed by fine-needle aspiration cytology. Case Presentation: A 49-year-old male presented with a 7 cm, slowly enlarging, subcutaneous mass in the left thigh of 20 years’ duration. Magnetic resonance imaging raised the possibility of a low-grade sarcoma. Fine-needle aspiration cytology yielded cohesive clusters of basaloid cells with peripheral palisading, delicate spindle-shaped follicular stromal cells intimately admixed with the epithelial component, and orangeophilic keratinous material in the background. The absence of nuclear atypia, mitotic figures, and mucinous stroma supported a preoperative cytological diagnosis of a benign follicular germinative tumor consistent with trichoblastoma, thereby guiding conservative surgical excision. Histopathological examination confirmed the diagnosis. Immunohistochemistry revealed focally positive BerEP4, CD34-positive stroma, negative androgen receptor, and positive bcl-2, consistent with trichoblastoma and distinguishing the tumor from basal cell carcinoma. The patient remained recurrence-free 12 months after surgery. Conclusions: Careful assessment of characteristic cytomorphological features, particularly a dual population of basaloid epithelial cells with peripheral palisading and specialized follicular stromal cells, is vital for the accurate preoperative cytological characterization of trichoblastoma, even at atypical anatomical sites. Full article

Background/Objectives: Keratinocyte carcinomas (KCs), including squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), are the most common malignancies worldwide. Accurate delineation of surgical margins is essential to ensure oncological control while preserving favourable aesthetic outcomes. Optical coherence tomography (OCT) is a non-invasive, real-time, high-resolution technique that may facilitate preoperative and intraoperative margin assessment. This systematic review aims to analyse existing evidence on the use of in vivo OCT in the assessment of surgical margins in KC. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The articles included were retrieved from the PubMed, Web of Science, Scopus and EBSCO databases. The search was limited to studies published between 2010 and November 2025. The inclusion criteria were the application of in vivo OCT as an adjunctive method in the surgical excision of KC. A total of 11 studies involving 303 patients met the inclusion criteria. OCT was used preoperatively, intraoperatively, combined pre- and intraoperatively and both pre-, intra- and postoperatively, with most studies focused on margin delineation by itself. Results: Agreement between OCT and histopathology ranges from 84% to 95.5%. Surgical benefits were observed in both conventional surgery and Mohs micrographic surgery, including reduction in MMS stages (1.89 to 1.23), fewer stages required, and narrower excision margins. Conclusions: Based on data analysis, it may be assumed that in vivo OCT may have potential in non-invasive margin assessment in the surgical treatment of KC. The available evidence is limited by the heterogeneity of protocols and devices and variability between lesion types, as well as the small sample sizes and limited comparability. Further research should focus on randomised multicentre trials involving large cohorts, cost–benefit analysis and evaluation of operator-dependent variability. Full article

Background: Eyelid malignancies require accurate intraoperative margin control to achieve complete tumor excision while preserving the functional and aesthetic integrity of the periocular region. Mohs micrographic surgery (MMS) is widely regarded as the reference standard for margin-controlled excision, whereas frozen section–controlled excision (FSC) represents a reliable and widely used alternative in oculoplastic practice. In parallel, several emerging imaging technologies are being investigated to improve real-time tumor detection and surgical precision. Methods: A narrative review of the literature was conducted to summarize current evidence on intraoperative margin control in eyelid tumor surgery. The review focused on established surgical techniques, including MMS and FSC, as well as emerging imaging modalities such as fluorescence confocal microscopy, reflectance confocal microscopy, optical coherence tomography, line-field confocal optical coherence tomography, photoacoustic imaging, and artificial intelligence (AI)-assisted analysis. Results: MMS provides complete circumferential peripheral and deep margin assessment and remains the benchmark for high-risk, recurrent, and poorly defined periocular tumors, particularly basal cell carcinoma. FSC offers favorable oncologic outcomes, allows immediate reconstruction, and remains an effective option when MMS is not available. Emerging imaging modalities have shown promising diagnostic performance for tumor detection, presurgical mapping, and intraoperative support, particularly in basal cell carcinoma, although evidence in periocular tumors remains limited for most techniques. AI-assisted approaches have also demonstrated high accuracy in the interpretation of frozen sections and optical imaging data, suggesting potential to improve workflow efficiency and diagnostic consistency. Conclusions: MMS and FSC remain the current standards for intraoperative margin control in eyelid tumor surgery. Emerging imaging technologies and AI-based tools may further enhance surgical precision and tissue preservation, but most remain investigational in the periocular setting. Further prospective studies are needed to validate their clinical utility, define standardized workflows, and clarify their role alongside established histopathologic techniques. Full article

Background: Angiogenesis is critical for tumor progression. Microvessel density (MVD) is commonly assessed using CD31 and CD34, which detect both mature and newly formed vessels and therefore cannot distinguish active neoangiogenesis from stable, quiescent vasculature. Nestin, an intermediate filament protein expressed preferentially in proliferating endothelial cells, has been proposed as a complementary marker of active angiogenesis and has been investigated in several solid tumor types, including pancreatic, colorectal, and breast carcinomas. However, no studies have quantitatively compared nestin-positive MVD across AK, BCC, and SCC using standardized methods. Methods: Immunohistochemistry for nestin, CD31, and CD34 was performed on 118 patient samples collected in 2015–2019 and diagnosed with AK, BCC, or SCC. MVD was quantified by averaging vessel counts in three representative “hot spot” areas. Results: Nestin-positive MVD was significantly lower in patients with AK compared to patients with BCC and SCC (p < 0.001). The mean MVD of nestin-positive vessels was significantly lower in AK than in BCC and SCC (p < 0.0001). In all three groups, nestin-positive MVD demonstrated a strong, positive correlation with both CD34 and CD31. Conclusions: Nestin-positive MVD was significantly elevated in BCC and SCC compared to AK lesions and demonstrated strong correlations with standard angiogenic markers. These findings suggest that nestin may warrant further investigation as a complementary marker of angiogenesis in non-melanoma skin cancer. Whether nestin-positive MVD offers independent diagnostic or prognostic value in this context remains to be determined in larger, prospective, multicentre studies. Full article

Background and Objectives: Invasive cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK) are growing burdens on ageing societies and mainly arise from chronic sun exposure. Distinguishing between carcinoma and carcinoma in situ is often clinically challenging but essential for decision-making with respect to targeted therapy. Ex vivo confocal laser scanning microscopy (CLSM) allows histologic examination of native tissue using tissue reflection and nuclear fluorescence staining. The digital staining process almost perfectly mimics conventional haematoxylin and eosin (HE) staining. While the use of CLSM for basal cell carcinoma (BCC) diagnosis is well described, data on cSCC remain scarce. The aim of this study was to compare CLSM with conventional histology in diagnosing and distinguishing cSCC and AK in routine clinical practice. Materials and Methods: Between August 2022 and March 2024, 63 patients with clinically suspected invasive cSCC or AK were enrolled. Biopsy or excision specimens were examined by ex vivo confocal laser scanning microscopy (VivaScope^® 2500 M-G4) followed by acridine orange staining. All samples underwent subsequent routine histopathology, which served as the reference. Two dermatologists independently compared the CLSM findings with the histopathological diagnoses. Results: Eighty-one lesions suspected to be cSCC were assessed using CLSM. The diagnostic accuracy was high across specimen types: cSCC was correctly identified in 24/26 cases (92.3%), AK/Morbus Bowen in 16/17 cases (94.1%), cSCC filia (cutaneous squamous cell carcinoma metastases) in 3/3 cases (100%), and basal cell carcinoma in 9/9 cases (100%). The absence of a tumour was correctly recognized in 19/21 cases (90.5%). In five cases (6.2%), AK and early invasive cSCC could not be differentiated, reflecting the histopathological results. Conclusions: CLSM with digital HE staining is well suited for rapid cSCC and AK diagnosis and differentiation in clinical practice. Full article

Photodynamic therapy (PDT) is a minimally invasive treatment choice whose clinical success in dermatology relies on the interaction between a photosensitizer, light of an appropriate wavelength, and tissue oxygen, leading to reactive oxygen species generation and selective cytotoxicity. This narrative review summarizes contemporary mechanisms and clinical evidence supporting PDT across neoplastic, inflammatory, infectious, and esthetic indications. A comprehensive literature search included randomized trials when available, systematic reviews, meta-analyses, and guideline and consensus documents, complemented by mechanistic and translational studies relevant to clinical outcomes. In premalignant and neoplastic disease, strongest evidence supports field-directed PDT for actinic keratosis and high efficacy in Bowen’s disease, with favorable cosmetic outcomes and acceptable recurrence patterns. PDT plays a more selective role in basal cell carcinoma, particularly superficial and selected nodular lesions, while its routine use as monotherapy in squamous cell carcinoma remains limited by higher recurrence. Beyond oncology, PDT shows expanding utility in acne via sebomodulatory and immunomodulatory effects, and in infectious dermatoses through broad antimicrobial activity and biofilm disruption with low resistance potential. Cosmetic applications, including photorejuvenation, benefit from protocol tailoring and combination strategies that enhance penetration and remodeling. Overall, PDT is evolving into an adaptable therapeutic framework best positioned within mechanism-oriented, multimodal algorithms. Full article