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Objective: Hypoxia intensely drives the development of malignant tumors, including skin cutaneous melanoma (SKCM). S-phase kinase-interacting protein 2 (SKP2) is known to participate in the progression of human tumors. The purpose of this study is to explore whether SKP2 acts as a hypoxic response gene during SKCM progression. Material and Methods: SKP2 expression in SKCM tissues was analyzed using The Cancer Genome Atlas database. Anoxic experiments were conducted to simulate an anoxic environment. 5-Ethynyl-2'-deoxyuridine and colony formation assays were used to evaluate SKCM cell growth. Scratch healing and Transwell assays were applied to measure the migration and invasion abilities of SKCM cells. An immunoblotting assay was used to detect the levels of extracellular signal-regulated kinase (ERK)1/2 pathway proteins. In addition, the ERK-specific agonist LM22B-10 was added to confirm whether the ERK1/2 signaling pathway is required for SKP2-mediated SKCM progression under hypoxic conditions. Results: SKP2 was significantly upregulated in SKCM tissues and closely related to adverse outcomes in patients. Moreover, SKP2 levels increased in SKCM cells under normoxic conditions and further elevated under hypoxic conditions. SKP2 deficiency led to the reduced proliferation, migration, and invasion potential of cells under hypoxic conditions. Mechanically, SKP2 silencing blocked the ERK1/2 pathway in hypoxic cells, and the activation of the ERK1/2 pathway rescued the suppression effect of SKP2 on the hypoxia-induced progression of SKCM. Conclusion: SKP2 deficiency repressed the hypoxic-induced progression of SKCM through the ERK1/2 pathway. This novel discovery regarding the SKP2/ERK1/2 axis might provide new insights into the pathogenesis of SKCM. [ABSTRACT FROM AUTHOR]

Purpose: To determine the dosimetric effects of set-up errors on boost coverage, and compares skin toxicity of sequential and simultaneous boost techniques for left-sided breast cancer. Materials and methods: This retrospective study included 23 early-stage breast cancer cases. Single isocenter HFWBI-SIB(s-SIB), single isocenter HFWBI-SB(s-SB) and dual isocenter HFWBI-SB(d-SB) were planing. Rotations of 0.5°, 1°, and 2° coupled with translationals of 0.5 mm, 1.0 mm, and 2.0 mm were applied along three orthogonal axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using GEE univariate analysis to determine how PTV coverage was related to 1/CIRTOG, PTVboost volume, PTVboost separation to isocenter. The relationship between the high-dose regions within the PTVbreast and Ratio_V was evaluated using univariate analysis. Results: The s-SIB had optimal target coverage and lower high-dose volume, but it increased the risk of compromised coverage to tumor bed. For the s-SB technique, V95 exceeded 95% under all setup errors. At 2.0° coupled with 2.0 mm, s-SIB and d-SB exhibited V95 values below 95% in 34.8% and 8.7% of cases, respectively. At other setup errors, both s-SIB and d-SB demonstrated V95 values greater than 95%. Notably, high-dose regions such as V105%, V107%, and V110% within the PTVbreast across the three techniques displayed a significant correlation with Ratio_V. Conclusion: Simultaneous-integrated boost for early-stage breast cancer can reduce skin toxicity compared to sequential techniques but with the risk of compromising tumor bed coverage. [ABSTRACT FROM AUTHOR]

Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) is made up of a heterogenous mix of both immune and non-immune cells as well as a multitude of signaling molecules. The interactions between tumor cells, immune cells and signaling molecules affect tumor progression and therapeutic responses. Understanding the composition and function of the TIME in primary cutaneous melanoma is useful for prognostication and therapeutic decisions. This review provides an overview of the components of the TIME in primary cutaneous melanoma, and their influence on clinical outcomes. [ABSTRACT FROM AUTHOR]

Nanofibrous dressing materials with an antitumor function can potentially inhibit recurrence of melanoma following the surgical excision of skin tumors. In this study, hydrolyzed polyacrylonitrile (hPAN) nanofibers biofunctionalized with L-carnosine (CAR) and loaded with bio (CAR)-synthesized zinc oxide (ZnO) nanoparticles, ZnO/CAR-hPAN (hereafter called ZCPAN), were employed to develop an antimelanoma wound dressing. Inspired by the formulation of the commercial wound healing Zn-CAR complex, i.e., polaprezinc (PLZ), for the first time, we benefitted from the synergy of zinc and CAR to create an antimelanoma nanofibrous wound dressing. According to scanning electron microscopy (SEM) images, ultrafine ZnO nanoparticles were homogenously distributed throughout the nanofibrous dressing. The ZCPAN nanofiber mat showed a significantly higher toughness (18.7 MJ.m−3 vs. 1.4 MJ.m−3) and an enhanced elongation at break (stretchability) compared to the neat PAN nanofiber mat (12% vs. 9.5%). Additionally, optical coherence elastography (OCE) measurements indicated that the ZCPAN nanofibrous dressing was as stiff as 50.57 ± 8.17 kPa which is notably larger than that of the PAN nanofibrous dressing, i.e., 24.49 ± 6.83 kPa. The optimum mechanical performance of the ZCPAN nanofibers originates from physicochemical interaction of CAR ligands, hPAN nanofibers, and ZnO nanoparticles through hydrogen bonding, electrostatic bonding, and esterification, as verified using ATR-FTIR. An in vitro cell viability assay using human skin melanoma cells implied that the cells are notably killed in the presence of the ZCPAN nanofibers compared to the PAN nanofibers. Thanks to ROS generating ZnO nanoparticles, this behavior originates from the high reactive oxygen species (ROS)-induced oxidative damage of melanoma cells, as verified through a CellROX assay. In this regard, an apoptotic cell response to the ZCPAN nanofibers was recorded through an apoptosis assay. Taken together, the ZCPAN nanofibers induce an antimelanoma effect through oxidative stress and thus are a high potential wound dressing material to suppress melanoma regrowth after surgical excision of skin tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard of care for the treatment of locally advanced periocular skin cancer is surgical resection, which commonly involves orbital exenteration, albeit normal vision in the majority of patients. The current study reports the long-term outcomes of using proton beam therapy as an eye-sparing approach in the treatment of locally advanced periocular skin cancer. Our findings suggest that proton beam therapy is an effective treatment, allowing tumor control while preserving functional vision in this group of patients. Background/Objectives: The management of periocular skin malignancies presents a unique challenge. Proton beam therapy, due to its sharp dose fall-off, allows for the delivery of a tumoricidal dose to the tumor while sparing adjacent normal tissues. Methods: Thirteen patients with a median age of 76.5 years received protons at our institution to a median dose of 66.6 Gy (RBE). Sixty-four percent of the lesions were basal cell carcinoma, and 22% were squamous cell carcinoma. Eighty-six percent of patients underwent biopsy only or partial resection. Fifty-seven percent of the lesions were located in the medial or lateral canthus. There was orbital invasion in 93% of the cases. Locoregional control probability and overall survival were estimated with the Kaplan–Meier method. Treatment toxicity was scored using the CTCAE 4.0. Results: At a median follow-up of 96 months, there was no local recurrence. The rate of orbital preservation was 100%. Functional vision was maintained in all the patients. There was no acute or late grade 3 or higher toxicity. Conclusions: Protons allow for long-term tumor control with eye preservation in patients with locally advanced periocular skin cancers. Larger prospective multi-institutional trials with standardized ophthalmological assessments are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with limited treatment options, highlighting the urgent need for novel therapeutic approaches, particularly those that can act locally. This study investigates a plasma-assisted method aimed at enhancing the local delivery of oncology drugs, focusing specifically on topotecan (TPT), a potent topoisomerase I inhibitor. Although TPT demonstrates potent antitumor activity, its use in systemic treatments is limited by its inability to effectively cross the blood–brain barrier, making it a promising candidate for local therapy. In this study, a nebulizer was attached to the J-Plasma® device—a medically approved helium plasma jet—and used to directly deposit TPT onto GBM cells (U-251mg) grown in both 2D and 3D culture systems. This method led to a reduction in cell metabolic activity, mass, and survival, indicating enhanced drug uptake and therapeutic efficacy. Additionally, the standard GBM treatment temozolomide (TMZ) and two skin cancer cell lines were tested, further supporting the potential of plasma-based drug delivery. These findings open new avenues for innovative local therapies that could potentially extend to a variety of cancers. Background/Objectives: Despite the numerous advances in glioblastoma multiforme (GBM) treatment, GBM remains as the most malignant and aggressive form of brain cancer, characterized by a very poor outcome, highlighting the ongoing need for the development of new therapeutic strategies. A novel intervention using plasma-assisted local delivery of oncology drugs was developed to mediate the drug delivery, which might improve drug uptake and/or chemotherapeutic action. Topotecan (TPT), a water-soluble topoisomerase I inhibitor with major cytotoxic effects during the S-phase of the cell cycle, was selected as the candidate drug because despite its potent antitumor activity, the systemic administration to the brain is limited due to low crossing of the blood-brain barrier. For these reasons, TPT may be repurposed for local combined therapies. Methods: We aimed to explore options for the local treatment of GBM where systematic delivery is challenging, using a combination between plasma-based technologies and TPT on a human brain cancer cell line (U-251mg). Results: The evaluation of direct TPT plasma deposition using a helium plasma jet (J-Plasma, Apyx Medical) with a nebulizer onto U-251mg cells grown in 2D or 3D culture showed a reduction in the metabolic activity and cell mass and decreased long-term survival, indicating synergistic effects between the drug and the plasma treatment. The plasma-assisted approach was confirmed using temozolomide (TMZ) as a standard drug for glioblastoma treatment, as well as with two skin cancer cell lines. Conclusions: These results revealed a pathway for new combinations and approaches to local drug application for a range of cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Basal cell carcinoma (BCC) is the most common form of skin cancer with different levels of aggressiveness depending on the subtype. High-risk BCCs can be suspected when the correlation of certain vascular and structural features occurs, especially in areas like the nose, eyes and ears. On the other hand, pigmented features have been found to be more common in less aggressive subtypes. Dermoscopy, a non-invasive diagnostic tool, improves early detection of BCC and helps in determining the subtype. Nevertheless, dermoscopic challenges remain, particularly in the case of lesions located on the lower limbs. Introduction: Basal cell carcinoma (BCC) is the most prevalent type of skin cancer worldwide. Despite its low metastatic potential, certain subtypes present an aggressive clinical course. Part II focuses on the different dermoscopic patterns observed in BCC, depending on the lesion subtype, its location on the body, the patient's age, the size of the tumor, and skin phototype. Methods: A search of the PubMed database was conducted for studies reporting dermoscopic findings in BCC across all body locations, histopathologic subtypes, tumor sizes, ages of onset and skin phototypes. Results: There are no dermoscopic features indicative of a particular BCC subtype. However, arborizing, truncated or glomerular vessels, shiny white lines, ulceration, white areas, absence of pink zones and large blue-gray ovoid nests suggest high-risk BCCs (morpheaform, micronodular, infiltrative, basosquamous). Pigmented features can occur in all BCC types, though increased pigmentation indicates less aggressive subtypes (nodular, superficial, fibroepithelioma of Pinkus, adenoid). BCCs most commonly develop on the head, typically presenting as nodular and non-pigmented tumors. Those on the nose, eyes and ears may be more aggressive and prone to recurrence. On the trunk, BCCs are usually superficial and pigmented. Lower limb lesions often show polymorphous vessels rather than arborizing ones, which makes the dermoscopic diagnosis challenging. Dermoscopy aids early detection, with larger tumors exhibiting more established features but no size-specific patterns. Aggressive subtypes display similar dermoscopic findings regardless of size. Conclusions: Dermoscopy is a valuable tool for the early detection of BCC, though no specific dermoscopic features can definitively identify subtypes. High-risk BCCs can be suspected when distinct vascular and structural patterns are present, particularly in lesions located on the face, especially around the nose, eyes and ears, while pigmented features may indicate less aggressive subtypes. [ABSTRACT FROM AUTHOR]

Background/Objectives: High-frequency ultrasound (HFUS) has been reported to be useful for the diagnosis of cutaneous diseases; however, its two-dimensional nature limits the value both in quantitative and qualitative evaluation. Three-dimensional (3D) visualization might help overcome the weakness of the currently existing HFUS. Methods: 3D-HFUS was newly developed and applied to various skin tumors and inflammatory hair diseases to assess its validity and advantages for dermatological use. Results: Three-dimensional images were successfully obtained from skin tumors, including basal cell carcinoma, subungual squamous cell carcinoma, Bowen's disease, and malignant melanoma, as well as inflammatory hair loss diseases including alopecia areata in different disease phases and lichen planopilaris. Vertical and horizontal images were generated from the original 3D image data and assessed in comparison with histopathological and/or dermoscopic images. By additionally obtaining horizontal data, lateral tumor margins at any depth were visualized in tumors. In inflammatory hair loss diseases, signs potentially associated with disease activity and pathology were detected. In addition, horizontal evaluation helped grasp hair cycle status and hair follicle densities. Conclusions: These findings suggested that this novel technology holds promise as a robust noninvasive tool to diagnose and evaluate various cutaneous diseases. [ABSTRACT FROM AUTHOR]

Background and Clinical Significance: Spiradenoma is a rare benign skin adnexal tumor with unknown incidence and prevalence, typically affecting young to middle-aged adults without a sexual predilection. Case Presentation: A 59-year-old woman presented with a palpable lesion in the suprapubic region that had been there for 20 years and had become enlarged over the past 2 months. Physical examination revealed a firm, non-tender, subcutaneous mass, approximately 2 cm in size, in the right pubic region. Ultrasound revealed a hypoechoic, heterogeneous lesion with a well-defined border, measuring 2.37 × 0.94 × 1.67 cm, without hypervascularity. Therefore, the patient underwent excision of the subcutaneous tumor. The pathology report confirmed the diagnosis of spiradenoma of the pubis. Histochemistry showed that the inner luminal cells were positive for CK7, and the outer basaloid cells were positive for p63. CD56 and CD117 were focally positive. Conclusions: With an accurate diagnosis and appropriate surgical excision, the prognosis for spiradenoma is generally excellent. However, a long-term follow-up is advisable. [ABSTRACT FROM AUTHOR]

Typical epidermodysplasia verruciformis (EV) is a rare, autosomal recessive disorder characterized by an unusual susceptibility to infection with specific skin-trophic types of human papillomavirus, principally betapapillomaviruses, and a propensity for developing malignant skin tumors in sun exposed regions. Its etiology reflects biallelic loss-of-function mutations in TMC6 (EVER1), TMC8 (EVER2) or CIB1. A TMC6-TMC8-CIB1 protein complex in the endoplasmic reticulum is hypothesized to be a restriction factor in keratinocytes for βHPV infection. However, the complex is also present in lymphocytes and its loss may compromise cellular immune control of βHPV infection. Indeed, certain primary immunodeficiencies, iatrogenic immunosuppression and AIDS are associated with the atypical form of EV. While well controlled in immunocompetent mice, murine papillomavirus MmuPV1 was first isolated from immunodeficient mice with florid skin warts, modeling atypical EV. To examine their potential as a model of typical EV, Tmc6-/-, Tmc8-/- or wildtype FVB mice were challenged with MmuPV1. At day 16 post vaginal challenge with MmuPV1, the levels of viral transcripts were similar in Tmc6-/- and Tmc8-/- mice and wildtype FVB mice, arguing against Tmc6/8 acting as intracellular restriction factors. Thereafter, greater clearance of MmuPV1 by the wildtype that the Tmc6-/- and Tmc8-/- FVB mice was evident, supporting the hypothesis that typical EV reflects a subtle cellular immune deficit. Indeed, Tmc6-/- or Tmc8-/- mice exhibit partial CD8 T cell deficits and elevated Treg. While interferon-γ production and surface CD25 were similarly elevated in CD8 T cells upon in vitro stimulation with anti-CD3/CD28, the fraction of Tmc6-/- or Tmc8-/- CD8 T cells that were dividing was lower compared to wildtype. Typical EV patients exhibit normal control of most viral infections; Tmc6-/-, Tmc8-/- and wildtype FVB mice similarly controlled vaccinia virus after skin challenge and induced neutralizing antibodies. Author summary: Typical epidermodysplasia verruciformis (EV) patients carry biallelic disabling mutations in TMC6, TMC8 or CIB1, and suffer high rates of skin cancer in UV-exposed sites associated with human betapapillomavirus (βHPV)+ plane warts. βHPV infections are common, but asymptomatic in healthy individuals. Typical EV is not associated with enhanced susceptibility to other infectious agents, and is proposed to reflect a loss of keratinocyte-intrinsic immunity specific for βHPV. Atypical EV is driven by certain inherited T cell deficits, AIDS or immunosuppressive drugs. βHPV and mouse papillomavirus MmuPV1 each lack E5, utilize similar oncogenic pathways, and synergize with UV and immunosuppression to promote skin cancer. We show establishment of MmuPV1 infection is similar to wildtype FVB mice, but thereafter more persistent in Tmc6-/- or Tmc8-/- mice. Tmc6-/- or Tmc8-/- mice exhibit partial CD8 T cell deficits and elevated Treg, but normal control of vaccinia, implying typical EV actually reflects subtle T cell dysfunction. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo describe a technique using retroauricular scalp graft for eyebrow reconstruction, along with problems encountered and countermeasures in treatment.We present a patient with eyebrow loss following resection of a malignant schwannoma. We initially covered the defect from the upper eyelid to the eyebrow area with artificial dermis for hemostasis and to increase the granulation of the graft bed. Considering hair texture, aesthetic unit and color match, the eyebrow area was grafted with a scalp harvested from the retroauricular region. The skin from the subclavian area was used for the upper eyelid defect. Tie-over fixation was performed.After a slightly longer immobilization period of 8.5 days, the tie-over fixation was removed. All grafted scalp and skin were fully engrafted. The reconstructed eyebrows had natural hair flow and softness. The texture of retroauricular hair closely resembled that of natural eyebrow hairs. The color and texture the upper eyelid grafts were also matched well. Surgical scar at the retroauricular hairline was effectively concealed by surrounding hair.Eyebrow reconstruction could be successfully achieved using from the retroauricular scalp with some ingenuity in order to be successful. These include improving the hemodynamic status of the grafted bed, considering aesthetic units, and extending the fixation period. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next‐generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel. Gene expression in DPAC was compared to that in hidradenoma (n = 10). Immunohistochemistry was employed to validate gene expression.Two out of eight DPACs showed fusion gene rearrangements (CRTC3::MAML2 and TRPS1::PLAG1). No uniform mutational signature was detected in DPAC. Comparative gene expression analysis revealed an enrichment of genes related to matrix remodeling, metabolism, and DNA damage repair. Hallmark pathway analysis demonstrated significant upregulation of E2F target genes in DPAC compared to hidradenoma (p = 0.00710). Human papillomavirus‐42 was found to be positive in all of our tested DPAC cases. Immunohistochemistry confirmed increased protein expression of CD56, CDC20, and SOX10 in DPAC. Notably, most DPAC tumors also exhibited B‐cell infiltration, as indicated by CD20 staining.Our findings reveal novel fusions and validate altered replication pathways related to HPV42 in DPAC. [ABSTRACT FROM AUTHOR]

Accurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC. We employed explainability analysis to reveal new insights into mortality risk factors for this highly aggressive cancer. We then combined deep learning feature selection with a modified XGBoost framework, to develop a web-based prognostic tool for MCC termed 'DeepMerkel'. DeepMerkel can make accurate personalised, time-dependent survival predictions for MCC from readily available clinical information. It demonstrated generalizability through high predictive performance in an international clinical cohort, out-performing current population-based prognostic staging systems. MCC and DeepMerkel provide the exemplar model of personalised machine learning prognostic tools in aggressive skin cancers. [ABSTRACT FROM AUTHOR]

Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location and anatomical characteristics. The treatment of these lesions is complex, and literature postulates Mohs surgery as the best therapeutic option. Methods: We describe our experience in two patients with the resection of vulvar lentiginous melanoma and genital extramammary Paget's disease, using a method of deferred lateral margin control in the surgical treatment. Results: The "spaghetti technique"(ST) initially removing a small strip from all lateral margins of the lesion, which is then closed directly while awaiting the paraffin histological result. In a second stage, the tumors within those margins are removed, and immediate reconstruction is performed. The final oncological and functional result was satisfactory, with no notable side effects. Conclusions: This method is suited for large, poorly defined superficial tumors in the genital, perineal, and perianal regions, where a frozen section study would be slow and burdensome for the patient and surgeon. The ST preserves healthy tissue and can be performed by any surgeon and pathologist without additional training, and is more comfortable for patients, avoiding prolonged open wounds during multiple steps of tumor excision. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to evaluate the safety and efficacy of chitosan-based bioadhesive films for facilitating the topical delivery of curcumin in skin cancer treatment, addressing the pharmacokinetic limitations associated with oral administration. Methods: The films, which incorporated curcumin, were formulated using varying proportions of chitosan, polyvinyl alcohol, Poloxamer® 407, and propylene glycol. These films were assessed for stability, drug release, in vitro skin permeation, cell viability (with and without radiotherapy), and skin irritation. Results: The films demonstrated physical stability and preserved curcumin content at room temperature for 90 days. Drug release was effectively controlled during the first 8 h, with release rates ranging from 51.6 ± 4.8% to 65.6 ± 13.0%. The films also enhanced drug penetration into the skin compared to a curcumin solution used as a control (stratum corneum: 1.3 ± 0.1 to 1.9 ± 0.8 µg/cm²; deeper skin layers: 1.7 ± 0.1 to 2.7 ± 0.2 µg/cm²). A cytotoxicity test on metastatic melanoma cells showed that curcumin at topical doses exerted activity similar to that delivered via the skin. Furthermore, curcumin alone was more effective in inhibiting tumor cells than radiotherapy alone (p < 0.01), with no additional benefit observed when curcumin was combined with radiotherapy. Finally, irritation tests confirmed that the films were safe for topical application. Conclusion: The developed chitosan-based bioadhesive films represent a promising alternative for the topical treatment of skin tumors using curcumin. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanocytic lesions, such as moles and melanomas, can be challenging to diagnose accurately. While current methods like conventional histopathologic analysis are time-consuming, this study explores the use of ex vivo confocal laser scanning microscopy (EVCM), a rapid imaging technique, to examine fresh tissue immediately after surgical removal. Our goal was to identify specific morphologic features and assess how well EVCM can differentiate between benign and malignant lesions. The results showed that EVCM can provide accurate and quick diagnoses, which could help as an adjunct to conventional histopathology and speed up treatment. Objective: Ex vivo confocal laser scanning microscopy (EVCM) is an emerging imaging technique, which offers rapid tissue examination. While the current literature shows promising results in the evaluation of non-melanoma skin cancer, only limited research exists on the application of EVCM in melanocytic lesions. This study aimed to assess the utility of EVCM in the characterization of melanocytic lesions and compare its findings with gold-standard histopathology. Methods: A total of 130 skin lesions, including 76 benign and 54 malignant melanocytic lesions, were prospectively collected and imaged using EVCM. Three blinded investigators were asked to identify characteristic morphologic features observed in the lesions and classify them into benign vs. malignant. The results were then compared with the corresponding histopathology. Sensitivity and specificity were calculated using contingency tables to assess the diagnostic performance. Results: The application of EVCM allowed for the visualization of cellular and tissue-level details, including cellular pleomorphism and atypical melanocytes. A comprehensive list of benign and malignant features identified by EVCM was compiled. Using these diagnostic criteria, the imaging of the inexperienced and dermatohistopathology-experienced investigator reached 67.7% concordance, and the imaging trained dermatologist obtained 69.2% agreement with dermatohistopathology in differentiating benign vs. malignant lesions. The imaging-trained dermatohistopathologist performed best with concordance up to 79.2%. Conclusions: In conclusion, EVCM is a promising technique for the rapid assessment of melanocytic lesions. Our study provides a comprehensive overview of morphologic EVCM features, which will contribute to the development of diagnostic algorithms for accurate diagnosis and appropriate treatment planning. Further studies are needed to evaluate its clinical utility and validate our diagnostic criteria. [ABSTRACT FROM AUTHOR]

Simple Summary: This study utilized datasets from two ethnic groups to develop an AI diagnostic model. This model was trained using transfer learning, leveraging eight pre-trained models, including convolutional neural networks and vision transformers. The three-class AI model assists doctors in distinguishing between patients with melanoma who require urgent treatment, those with non-melanoma skin cancers who can be treated later, and benign cases that do not require intervention. The proposed two-stage classification strategy significantly improved diagnostic accuracy and reduced false negatives. This research demonstrates the success of the proposed method in both datasets. These findings highlight the potential of AI technology in skin cancer diagnosis, particularly in resource-limited medical settings, where it could become a valuable clinical tool to improve diagnostic accuracy, reduce skin cancer mortality, and decrease healthcare costs. Background: Skin cancer is the most common cancer worldwide, with melanoma being the deadliest type, though it accounts for less than 5% of cases. Traditional skin cancer detection methods are effective but are often costly and time-consuming. Recent advances in artificial intelligence have improved skin cancer diagnosis by helping dermatologists identify suspicious lesions. Methods: The study used datasets from two ethnic groups, sourced from the ISIC platform and CSMU Hospital, to develop an AI diagnostic model. Eight pre-trained models, including convolutional neural networks and vision transformers, were fine-tuned. The three best-performing models were combined into an ensemble model, which underwent multiple random experiments to ensure stability. To improve diagnostic accuracy and reduce false negatives, a two-stage classification strategy was employed: a three-class model for initial classification, followed by a binary model for secondary prediction of benign cases. Results: In the ISIC dataset, the false negative rate for malignant lesions was significantly reduced, and the number of malignant cases misclassified as benign dropped from 124 to 45. In the CSMUH dataset, false negatives for malignant cases were completely eliminated, reducing the number of misclassified malignant cases to zero, resulting in a notable improvement in diagnostic precision and a reduction in the false negative rate. Conclusions: Through the proposed method, the study demonstrated clear success in both datasets. First, a three-class AI model can assist doctors in distinguishing between melanoma patients who require urgent treatment, non-melanoma skin cancer patients who can be treated later, and benign cases that do not require intervention. Subsequently, a two-stage classification strategy effectively reduces false negatives in malignant lesions. These findings highlight the potential of AI technology in skin cancer diagnosis, particularly in resource-limited medical settings, where it could become a valuable clinical tool to improve diagnostic accuracy, reduce skin cancer mortality, and reduce healthcare costs. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we sought to understand the role of NF2 gene mutation in the carcinogenesis of sporadic cancers. NF2 gene mutations are noted in several central nervous system tumors, solid-organ tumors, and skin cancers. We conducted a literature review on eleven different cancers with NF2 gene mutation involvement, summarizing the extent of association and specific biological pathways thought to be affected by NF2 mutations. We synthesized studies across several oncologic fields to consolidate what we know about NF2 gene mutations in cancer development. The Hippo signaling pathway is a biological pathway that is involved in eight of the eleven NF2-mutated cancers studied in this review. Although NF2 mutation has a known interaction with the Hippo signaling pathway, the specific details of this interface remain a topic for further studies. Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological pathways implicated in cancer formation resulting from sporadic NF2 mutations. Results: NF2 gene mutations are implicated in over 11 different cancers, including several CNS tumors, soli-organ tumors, and skin cancer. NF2 acts as a driver mutation in some cancers, as a non-driver mutation in some cancers, and has simple associated mutations with other cancers. In terms of biological pathway involvement, 8 of the 11 cancers with NF2 mutations show evidence of Hippo signaling cascade involvement. Conclusions: Several cancers characterized by mutations in the NF2 gene have associations with the Hippo signaling pathway. However, future studies remain to be done to further elucidate the role of the Hippo signaling pathway in the carcinogenesis of human NF2-mutant tumors. The findings of this review provide insights into the role of NF2 mutations in cancers, Hippo signaling in NF2-mutant cancers, and current gaps in our knowledge regarding the two. [ABSTRACT FROM AUTHOR]

Simple Summary: Nevoid melanoma is a rare melanoma subtype that closely resembles a common nevus clinically and histologically. For this reason, diagnosis is easily missed. Both dermatologists and pathologists should be aware of this entity since its recognition might avoid severe consequences for the patient and medicolegal issues. Only a few papers on clinical and dermoscopic characteristics of nevoid melanoma are available. This study analyzes the clinical and pathological characteristics of nevoid melanoma in a population of patients affected by this rare subtype. It compares the prognosis and survival of these patients to data from classical melanoma featured in the literature. Additionally, by analyzing available dermoscopic images of nevoid melanoma, we aim to identify dermoscopic features that might help clinicians to suspect nevoid melanoma, reducing misdiagnosis. Background: Diagnosis of nevoid melanoma (NeM) is often difficult because NeM closely resembles a common nevus clinically and histologically. Methods: A retrospective study was conducted on 110 patients diagnosed with and/or treated for primary nevoid melanoma at the Veneto Institute of Oncology and at the University Hospital of Padua from August 1999. Results: Mean Breslow thickness was of 1.4 mm. Sentinel lymph node biopsy was conducted in nearly half of the patients, and positivity was detected in 16.7% of them. Twenty-four clinical and 23 dermoscopic pictures were collected. Papular and macular lesions prevailed over nodular and plaque-type lesions. Different hues of brown, pink, and red color were most represented. Twenty nevus-like NeMs and four multicomponent-pattern NeMs were observed. The Most frequent dermoscopic patterns for nevus-like NeM were atypical pigmented reticulum, irregular globules and dots, and hyperpigmented blotches. Atypical vessels, asymmetric peripheric striae, blue-white veil, and areas of regression were less frequent and prevailed in multicomponent pattern NeM. A structureless pattern was also featured. Many patients in the series had multiple melanomas. However, none of them had numerous multiple nevoid melanomas. Conclusions: NeM should not be regarded as a separate biological entity from classical melanoma, and the same histological and clinical prognostic factors apply to NeM. Clinically and dermoscopically, it often resembles benign nevi, although some clues such as evolution and some dermoscopic patterns could suggest malignancy. Clinical suspicion might prove crucial to further pathological analysis and recognition. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancer ranks among the most prevalent malignancies globally. Current treatment for skin cancer involves surgery, chemotherapy, radiotherapy, and immunotherapy. Chemotherapy drugs have demonstrated resistance following several cycles, resulting in limited therapeutic possibilities for recurring and resistant cases. Targeting cancer metabolism to restrict cell growth may be a promising approach to increase the survival rates of skin cancer patients. One potential target is glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Inhibition of glucose-6-phosphate dehydrogenase activity could reduce cellular NADPH production, thereby increasing oxidative stress and limiting tumor progression. Skin cancer is one of the most prevalent malignancies in the world, with increasing incidence. In 2022, the World Health Organization estimated over 1.5 million new diagnoses of skin malignancies, primarily affecting the older population. Surgical excision, particularly in the head and neck area, can cause aesthetic deficits and significantly impair patients' quality of life. There are limited therapeutic options for advanced skin malignancies, and the development of resistance to targeted therapy further restricts treatment choices. Cancer metabolism may offer a novel approach to overcome these challenges. The pentose phosphate pathway, along with its rate-limiting enzyme, glucose-6-phosphate dehydrogenase, is essential for both the antioxidative response and the synthesis of ribonucleotides and may play a critical role in the proliferation and growth of cancer cells. This review examines current knowledge on the correlation between altered glucose-6-phosphate dehydrogenase expression and activity and skin cancer progression, with the aim of identifying a potential therapeutic target for treating advanced skin cancer. [ABSTRACT FROM AUTHOR]

Different types of feline papillomaviruses (PVs) are associated with a variety of skin lesions and neoplasia, such as papillomas and cell carcinomas, but the virus can also be found in healthy skin. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of veterinary experts on feline infectious diseases from 11 European Countries, discusses the current knowledge of feline PV infections. Cats most likely become infected through lesions or abrasions of the skin. Most PV infections remain asymptomatic. Besides cat-specific PVs, DNA sequences most closely related to human and bovine PVs have been detected in feline skin lesions. Diagnosis is supported by the histological detection of PV-induced cell changes and intralesional detection of viral antigen (immunostaining) or viral DNA (in situ hybridization). Immunostaining of p16CDKN2A protein (p16) can be performed as a proxy marker for PV-induced neoplasms. There is no specific treatment for PV-induced skin lesions. Spontaneous regression commonly occurs. In the case of invasive squamous cell carcinoma (ISCC), complete excision should be considered, if possible. [ABSTRACT FROM AUTHOR]

BACKGROUND: Malignant adnexal tumors of the skin are a rare group of tumors that can be locally aggressive and require surgical excision with strict margin control to achieve clearance. Given the rarity of these tumors, there is a limited understanding within the medical community regarding optimal treatment approaches. OBJECTIVE: To examine surgical management trends and outcomes for patients diagnosed with cutaneous adnexal tumors from 2000 to 2020. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify biopsy-proven cases of cutaneous adnexal tumors between 2000 and 2020. Clinical and disease characteristics were examined, and disease-specific survivals were compared between surgical approaches using Kaplan–Meier curves and Cox proportional hazards models. RESULTS: Mohs surgery demonstrated a significant increase in utilization from 2000 to 2020 (+447.1%) and improvements in disease-specific survival (mean 231.7 months; p <.001) compared with no surgery; wide local excision exhibited no improved disease-specific survival (227.7 months; p =.070). Multivariable Cox regression further highlighted that only Mohs surgery exhibited a reduced disease-specific mortality risk compared with no surgery (adjusted HR 0.49; p =.011). CONCLUSION: Given the enhanced disease-specific survival coupled with tissue preservation strategies, Mohs surgery emerges as a promising surgical approach for the treatment of malignant adnexal tumors of the skin. [ABSTRACT FROM AUTHOR]

Introduction: Ultraviolet-induced fluorescence dermoscopy (UVF dermoscopy) is a novel diagnostic technique for identifying and diagnosing numerous skin tumors, inflammatory dermatoses, and infectious diseases. The ultraviolet (UV) band has a wavelength ranging from 10 to 400 nm. When intense UV radiation with shorter wavelengths strikes a target chromophore, visible light (VL) with a longer wavelength and lower energy is produced in the skin. This VL is apparent to the naked eye and is referred to as fluorescence. Aim: The current review compares ultraviolet fluorescence dermoscopy (UVFD) and polarized dermoscopy (PD) features in various dermatological disorders. Materials and Methods: This review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalyses) guidelines. A comprehensive search of the literature was carried out through the PubMed and Google Scholar electronic databases from inception to 25th December 2023 using the following search terms: "UV dermoscopy" OR "ultraviolet fluorescence dermoscopy" OR "ultraviolet-induced fluorescence dermoscopy" OR "Ultraviolet-induced fluorescent dermoscopy". Titles, abstracts, and full texts were screened by two independent reviewers to select papers dealing with UVF-dermoscopy. Results: A total of 23 relevant articles were included in this systematic review, including a total of 313 patients. Pigmented skin tumors included 209 patients, Fordyce spot mimickers (13), scabies (57), biopsy site (20), psoriasis (3), corynebacterium infections (2), fungal infections (4), vitiligo (3), acne folliculitis (1) and glomus tumors (1). Levels of evidence (LoE) was 3 and 4 in only two included studies; the rest had a LoE of 5. Discussion: UVF dermoscopy is a new diagnostic and prognostic tool for neoplastic and non-neoplastic dermatological conditions. This is the first systematic review of its sort that compares and categorizes dermoscopic findings in UVF and polarized light in dermatological practice. As UVFD does not penetrate deeper skin layers, we observed that it is a better way to distinguish features restricted to the skin's superficial layers in neoplastic diseases. As a result, tumor-free margins and improved surgical outcomes can be achieved. More favorable outcomes for evaluation and treatment were seen with non-neoplastic conditions. Limitations included a lack of studies with a high level of evidence, control groups, and larger sample sizes. Conclusion: We concluded that UVFD will improve clinical diagnosis, disease management, and outcomes. More clinical trials with larger sample sizes are recommended to better understand this novel and intriguing new diagnostic tool. [ABSTRACT FROM AUTHOR]

Background: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. Objectives: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. Methods: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super‐categories (e.g. 'benign') and cellular/tissue‐differentiation categories (e.g. 'melanocytic'), and appended with pertinent‐modifiers and synonyms. These terms were evaluated using a modified‐Delphi consensus approach. Experts from the International‐Skin‐Imaging‐Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. Results: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign‐category terms, 6/140 (4%) malignant‐category terms and 6/13 (46%) indeterminate‐category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super‐categories and 41 cellular/tissue‐differentiation categories. Conclusions: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon. [ABSTRACT FROM AUTHOR]

Atypical fibroxanthoma (AFX) is a dermal spindle-cell cutaneous malignancy, which is a relatively benign type of skin cancer that occurs in the elderly with sun-damaged skin. This is a case study of a rapidly enlarged left auricular mass lesion in an elderly patient who was diagnosed with AFX based on histopathological and immunohistochemical findings, and then treated by complete excision to prevent recurrence or metastasis. There was no recurrence during the 1-year follow-up. For otolaryngologists or plastic surgeons, recognizing the clinical and pathologic characteristics of AFX is important for accurate diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: While electrochemotherapy (ECT) is increasingly utilized as a highly effective method in the treatment of tumors in the head and neck region, there is significantly less data available for eyelid‐periocular skin tumors. Our group reported the first extensive case series of eyelid‐periocular basal cell carcinoma (BCC) patients with short‐term follow‐up treatment with ECT. The present study aims to report our long‐term results of eyelid‐periocular BCC cases treated with ECT. Methods: The treatments were performed according to the ESOPE (European Standard Operating Procedures on Electrochemotherapy) guidelines using the Cliniporator™ device. All patients received bleomycin‐based ECT, administered intratumorally or intravenously. Tumor response was evaluated using the RECIST 1.1 criteria. Results: The results of 19 patients treated with ECT are presented. Four patients had locally advanced primary tumors, while 15 patients had recurrent tumors. Bleomycin was administered intratumorally in four patients and intravenously in 15 patients. The overall response was 100%, while the complete response rate proved to be 95%. In three cases (15.8%), recurrence was observed during the mean follow‐up period of 78.9 months. Conclusions: ECT can effectively treat locally advanced or recurrent BCC in the eyelid‐periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with long interval follow‐up. [ABSTRACT FROM AUTHOR]

Wolf isotopic response (WIR) is a phenomenon in which a second, unrelated skin disease arises at the same site as a previously healed dermatosis. WIR most commonly occurs in healed herpes zoster but has also been described in other conditions, such as herpes simplex virus, varicella‐zoster virus, and skin tumors. Acquired perforating dermatosis (APD) is characterized by transepidermal elimination of collagen bundles that lead to the development of ulcerative papules, which are often associated with systemic conditions such as diabetes or renal failure. This report documents a rare occurrence of APD after WIR and reviews related published works. [ABSTRACT FROM AUTHOR]

In the updated 5th edition of the WHO Classification of Skin Tumors, primary cutaneous cribriform carcinoma has been renamed cribriform tumor. This entity is a rare sweat gland neoplasm with undetermined malignant potential, with only 46 cases reported to date. Herein, we present a case of a 30‐year‐old female with a solitary nodule in the left thigh subcutaneous tissue. Histopathological examination revealed a well‐defined dermal nodule composed of monomorphic, deeply staining cells arranged in solid nests, tubular, and cribriform patterns, with no recurrence or distant metastasis observed during a 1‐year follow‐up. Summarizing all 47 cases, they exhibited consistent, reproducible histological morphology and similar immunohistochemistry. Although the tumor nests lacked myoepithelial cells peripherally, all cleanly excised cases showed no recurrence or distant metastasis, suggesting a benign biological behavior. We argue against overtreatment. [ABSTRACT FROM AUTHOR]

Aim: This article aims to examine the demographic and clinical traits of neurofibromatosis type 1 (NF1) patients, particularly focusing on the potential links between vitamin D levels, BMI, and dermatological features. Methods: A retrospective review of medical records involving 128 patients diagnosed with neurofibromatosis type 1 (NF1) over a 3-year-period was conducted. The analysis emphasized investigating the demographic and clinical characteristics of the patients while evaluating key parameters. Result: Nevus anemicus was present in 32.8% of NF1 patients, and a significant association was found between nevus anemicus and low vitamin D levels (P = 0.001). We also observed a notable correlation between low vitamin D levels and an increased likelihood of neurofibromas (P < 0.001). Additionally, there appears to be an inverse relationship between serum vitamin D levels and the number of neurofibromas. Conclusion: Our study suggests a correlation between lower vitamin D levels and key dermatological characteristics in neurofibromatosis type 1 (NF1) individuals. Specifically, we observed associations with nevus anemicus prevalence and increased neurofibromas. This observation enriches NF1's understanding, offering practical implications for patient management by emphasizing the importance of monitoring and addressing vitamin D levels. [ABSTRACT FROM AUTHOR]

This study aimed to identify factors influencing the completeness of primary and re-excision of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and cutaneous carcinoma in situ (CIS) of the head and neck. A retrospective single-center analysis was conducted, encompassing 1513 instances of cutaneous tumors recorded between 2015 and 2022. This dataset comprised 1108 primary excisions and 405 re-excisions, all of which were histologically verified cases of BCC, SCC, and CIS located within the head and neck region. Correlation analyses were performed, considering variables such as patients' gender and age, tumor localization, preoperative suspicion or histological confirmation of skin tumor diagnosis, surgeons' levels of training, and the utilization of magnifying glasses. The primary objective was to assess the impact of these factors on the completeness of both primary and re-excisions of skin tumors. The analysis revealed a significant correlation between the localization of BCC and the completeness of primary excision. Specifically, the nose and ear exhibited a significantly higher rate of incomplete excisions (R1), whereas the cheek demonstrated a substantial reduction in the R1 rate. The utilization of magnifying glasses exhibited a positive correlation with the completeness of primary BCC excision. However, no discernible influencing factors were identified for BCC re-excisions and the combined group of primarily and re-excised cutaneous squamous cell carcinoma (SCC) and carcinoma in situ (CIS). Tumor entity and localization emerged as crucial factors influencing the completeness of skin tumor excisions, with specific anatomical sites exhibiting varying rates of incomplete procedures. Notably, the use of magnifying glasses demonstrated a significant positive correlation with reduced rates of incomplete excisions, re-excisions, and subsequent procedures, suggesting its potential as a valuable tool in enhancing surgical precision and optimizing outcomes. [ABSTRACT FROM AUTHOR]

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This study explores the advanced imaging of skin vasculature using Line-Field Confocal Optical Coherence Tomography (LC-OCT), which offers high-resolution, three-dimensional (3D) visualization of vascular structures, especially within skin tumors. The research aims to improve the understanding of tumor angiogenesis and the complex vascular morphology associated with malignancies. The methodology involves converting original image stacks into negative images, manually tracing vessels using the Simple Neurite Tracer (SNT) plugin, and creating smoothed binary masks to reconstruct 3D models. The study's results highlight the ability to visualize serpiginous, corkscrew-like, and irregular vessels across various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma. These visualizations provide insights into vessel morphology, spatial arrangements, and blood flow patterns, which are crucial for assessing tumor growth and potential therapeutic responses. The findings indicate that 3D reconstructions from LC-OCT can uncover vascular details previously undetectable by two-dimensional imaging techniques, making it a valuable tool in dermatology for both clinical diagnostics and research. This method allows for better monitoring of skin cancer treatment and understanding of the role of vascular polymorphism in tumor development. [ABSTRACT FROM AUTHOR]

Equine melanocytic neoplasm (EMN) represents a form of skin tumor observed predominantly in grey horses aged over 15 years. Despite its prevalence, current therapeutic and preventive strategies for EMN have been subject to limited investigation. This study endeavors to shed light on potential phosphoproteins present in equine serum and fecal samples, potentially linked to EMN, with a specific focus on functional interactions in EMN pathogenesis. We examined 50 samples (25 serum, 25 feces), divided into three groups based on EMN severity: normal (n = 16), mild (n = 18), and severe EMN (n = 16). Equine phosphoproteome analysis identified 2,359 annotated serum phosphoproteins and 2002 annotated fecal phosphoproteins through differentially expressed proteins (DEPs). KEGG analysis emphasized the role of environmental information processing. Notably, the integrin NF-kappaB binding P-TEFb to stimulate transcriptional elongation signaling pathway, involving SNW1 protein, was implicated in early stage of EMN development in both serum and fecal samples. This highlights SNW1's potential role in mediating transcriptional processes, offering a novel marker within environmental information processing. This study enhances understanding of EMN mechanisms in horses, suggesting early detection through non-invasive methods and identifying a functional pathway involving SNW1, which could inform future treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive form of skin tumor and leads to a high mortality (5.0–5.6 %) among all cancers. To increase efficiency of its treatment during local photodynamic therapy (PDT), we developed h-BN/n·MB heterostructures based on hexagonal boron nitride (h-BN) nanoparticles (NPs) and adsorbed methylene blue (MB) of various concentrations (n). Heterostructures containing 200 mg of MB per 1 g of h-BN (h-BN/200 MB), after their irradiation with an artificial sunlight source for 30 min, generated 3.7 × 10−2 ± 0.2 × 10−3 μM × μg−1 of reactive oxygen species (ROS) and reduced the viability of A-375 melanoma cells by 90 % after 48 h. The observed levels of oxidative and antitumor activity of the h-BN/200 MB hybrid material significantly exceed those of the individual system components, MB and h-BN. It is shown that MB adsorbed on h-BN NPs possesses enhanced stability and photooxidative activity. Adsorbed MB has almost not the dark phototoxicity inherent in the MB solution and demonstrates enhanced biocompatibility with normal fibroblasts Wi-38. The results demonstrate the promising potential of h-BN/n-MB heterostructures for melanoma PDT. [ABSTRACT FROM AUTHOR]

Macrophages, as specialized, long-lasting phagocytic cells of the innate immune system, have garnered increasing attention due to their wide distribution and various functions. The skin, being the largest immune organ in the human body, presents an intriguing landscape for macrophage research, particularly regarding their roles in inflammatory skin diseases and skin tumors. In this review, we compile the latest research on macrophages in conditions such as atopic dermatitis, psoriasis, systemic sclerosis, systemic lupus erythematosus, rosacea, bullous pemphigoid, melanoma and cutaneous T-cell lymphoma. We aim to contribute to illustrating the pathogenesis and potential new therapies for inflammatory skin diseases and skin tumors from the perspective of macrophages. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel Lymph Node Biopsy (SLNB) aims at the early detection of lymph node metastases. In the field of skin cancer, it is a standard staging procedure for patients with T1b to T4 primary cutaneous melanoma. When considering Non-Melanoma Skin Cancer (NMSC), the SNLB should be rationally considered in tumors with a typical lymphatic spread, including Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Porocarcinoma. However, the SLNB-NMSC criteria, thresholds, and guidelines are currently missing. Hereby, the role of SNLB in NMSC is reviewed. Background/Objectives: Sentinel Lymph Node Biopsy (SLNB) aims at identifying clinically occult nodal metastases. It is the standard staging procedure for patients with T1b to T4 primary cutaneous melanoma. Moreover, it is recommended whenever the risk of a positive SLNB is >5%, according to the National Comprehensive Cancer Network Melanoma guidelines. When considering Non-Melanoma Skin Cancer (NMSC), the SLNB could play a role in tumors that mainly spreads via lymphatics, but strong evidence is missing. In this paper, the hot topics and controversies are reviewed; Methods: A PRISMA systematic review was carried out on the PubMed (MEDLINE) library from 2004–2024, searching for studies on SLNB in NMSC; Results: Seventy articles and 6379 patients undergoing SLNB for Squamous Cell Carcinoma (SCC), Merkel Cell Carcinoma (MCC), and Porocarcinoma were included. Overall, the SLNB positivity rate in these NMSCs was 24.4%, with an SNLB detection rate of 97.6%. Specifically, the SLNB positivity rate was 12.3% for high-risk cutaneous SCC, 24.4% for anogenital SCC, 29.3% for MCC, and 30.6% for Porocarcinoma. Most papers concluded that SLNB is safe, feasible, and significant in these malignancies; Conclusions: SLNB should be discussed and offered to every patient with MCC, and it should be discussed and considered in "high risk" SCC and Porocarcinoma for staging and prognostic purposes, aiming to identify a subgroup of patients who may benefit the most from early treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Although melanoma is much less common than other skin cancers, it has a higher mortality rate and is responsible for almost 73% of skin cancer-related deaths. Dysplastic nevus (DN) is known as a key factor contributing to the development of cutaneous melanoma. Early detection and monitoring are crucial for individuals with atypical nevi. This study's aim was to investigate the role of selected risk factors in the incidence of skin cancers and the stage of advancement at diagnosis. Our study involved a group of younger people and highlighted several key factors influencing the occurrence of atypical skin lesions. However, it also focuses attention on the significant correlation between the occurrence of atypical lesions and various clinical and demographic factors in this age group. Our findings underscore the necessity for targeted prevention strategies and regular dermatologic screening, particularly for the high-risk groups identified in this study. Background/Objectives: Skin cancer is becoming increasingly common due to increasing risk factors such as excessive ultraviolet (UV) radiation, genetic predisposition, fair skin, and a history of sunburn. Melanoma accounts for only 1% of cases but causes most skin cancer deaths. Dysplastic nevi (DN) are important precursors of melanoma. The aim of this study was to investigate the influence of these risk factors on the incidence and stage of skin cancer. Methods: The study included 591 patients aged 18 to 64 who visited the Department of Dermatology and Venereology in 2022–2023 for skin examinations. Each patient completed a questionnaire regarding the risk factors for melanoma and atypical melanocytic nevi and then underwent a dermatoscopic examination of the whole body using a digital videodermatoscope. Results: Dermatoscopic examination revealed a lesion suggestive of melanoma in 1.69% of the patients. Risk factors for developing melanoma included male gender, family history of melanoma, number of skin moles, sunburn in childhood, sun-dependent hobby, using a tanning bed, using low sun protection factor (SPF) cream, not avoiding sun exposure, and co-occurrence of actinic keratosis. Conclusions: Risk factors for melanoma and dysplastic nevi are still common among patients, but the situation has been improving over the years. Early intervention and education on sun safety can play pivotal roles in reducing the incidence of atypical moles and potentially preventing malignant transformations. [ABSTRACT FROM AUTHOR]

Simple Summary: Psoriasis, a chronic inflammatory skin condition, is increasingly recognized for its complex interactions with various systemic diseases, including neoplasia. This article reviews the relationship between psoriasis and neoplasia, focusing on the risk factors for cancer in psoriasis patients, the implications of psoriasis treatments on cancer risk, and strategies for managing patients with both conditions. The association between psoriasis and increased cancer risk is gaining recognition as studies reveal shared inflammatory and immune pathways. This review examines the relationship between psoriasis and neoplasia, focusing on cancer risk factors in psoriasis patients, the biological pathways underlying this connection, and the impact of various psoriasis treatments on cancer development. Psoriasis patients have a heightened incidence of certain cancers, such as lymphomas, skin cancers, and urological malignancies, potentially linked to immune dysregulation and chronic inflammation. Immunomodulatory treatments for psoriasis, including conventional systemic therapies and biologics, present varied cancer risks, with others, such as phototherapy, associated with an elevated risk of skin cancers. For oncologic patients with psoriasis, management necessitates a tailored approach, balancing effective psoriasis control with minimizing cancer progression risks. The emergence of IL-17 inhibitors, IL-23 inhibitors, and small-molecule therapies offers promising therapeutic alternatives with favorable safety profiles for these patients. This review underscores the need for interdisciplinary collaboration to optimize care for patients managing both psoriasis and malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the link between skin cancer types and sun exposure or photoprotection habits in a Greek cohort on the island of Crete. It included 265 skin cancer patients (BCC, SCC, MM) and 106 healthy controls. The patients with skin cancer had lighter skin phototypes, higher sun exposure (occupational, leisure, and during childhood), and fewer photoprotection habits. The healthy controls used sunscreen more frequently, preferred SPF > 50, and were more likely to wear sunglasses, brimmed hats, and long-sleeved clothing. These findings highlight the need for targeted prevention strategies to reduce skin cancer risk by improving photoprotection practices, particularly in sun-exposed populations. Backgorund: This study aimed to explore the relationship between different types of skin cancer and factors such as sun exposure and photoprotection measures in a Greek cohort on the island of Crete. Methods: This cross-sectional observational study was conducted in the Dermatology Department of the University Hospital in Heraklion, Crete, between January 2019 and January 2024. The study population included consecutive patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM), as well as healthy controls. The participants completed a self-reported questionnaire covering demographic and clinical data as well as questions about sun exposure and photoprotection habits. Results: A total of 265 skin cancer patients and 106 healthy controls participated in the study: 50.6% of the patients had basal cell carcinoma, 35.1% had squamous cell carcinoma, and 14.3% had malignant melanoma. The cohort comprised 41.5% females and 58.5% males, with a mean age of 73.2 years. As expected, the patients with skin cancer had a lighter skin phototype compared to the healthy controls (p < 0.01). They also reported greater occupational (p < 0.01) and leisure sun exposure (p < 0.01) and a higher median number of vacation weeks spent outdoors before the age of 18 (p = 0.030). Furthermore, the healthy controls were more likely to use sunscreen (p = 0.035) and preferred higher SPF (>50) when they did so (p < 0.01). The healthy controls also reported more frequent use of sunglasses (p < 0.01), brimmed hats (p < 0.01), and long-sleeved clothing (p < 0.01) compared to the skin cancer patients. Conclusion: This is the first study to analyze sun exposure and photoprotection behaviors in patients with nonmelanoma skin cancer (NMSC) and malignant melanoma (MM) in Crete, revealing the key associations and underscoring the need for targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides a comprehensive overview of advancements in melanoma biomarkers, emphasizing the potential of serologic biomarkers for early diagnosis, prognosis, and personalized treatment of melanoma. Notable markers include S100B and lactate dehydrogenase (LDH), already partially integrated into clinical practice, and new candidates like melanoma-inhibiting activity (MIA), osteopontin, and tumor-associated antigen 90 immune complex (TA90-IC), which offer predictive capabilities for treatment outcomes. New biomarkers, including genetic, proteomic, and cellular markers, are emerging as crucial tools. These biomarkers, such as circulating tumor DNA (ctDNA) and RNA, can offer real-time insights into tumor dynamics, enabling non-invasive monitoring through liquid biopsies. Additionally, tumor-educated platelets and circulating immune cells show promise in understanding melanoma's aggressive behavior. Lastly, the review discusses the integration of these biomarkers into clinical protocols and the need for continued research to establish these tools' accuracy, improving patient-specific treatment strategies. Melanoma is one of the most malignant cancers, and the global incidence of cutaneous melanoma is increasing. While melanomas are highly prone to metastasize if diagnosed late, early detection and treatment significantly reduce the risk of mortality. Identifying patients at higher risk of metastasis, who might benefit from early adjuvant therapies, is particularly important, especially with the advent of new melanoma treatments. Therefore, there is a pressing need to develop additional prognostic biomarkers for melanoma to improve early stratification of patients and accurately identify high-risk subgroups, ultimately enabling more effective personalized treatments. Recent advances in melanoma therapy, including targeted treatments and immunotherapy, have underscored the importance of biomarkers in determining prognosis and predicting treatment response. The clinical application of these markers holds the potential for significant advancements in melanoma management. Various tumor-derived genetic, proteomic, and cellular components are continuously released into the bloodstream of cancer patients. These molecules, including circulating tumor DNA and RNA, proteins, tumor cells, and immune cells, are emerging as practical and precise liquid biomarkers for cancer. In the current era of effective molecular-targeted therapies and immunotherapies, there is an urgent need to integrate these circulating biomarkers into clinical practice to facilitate personalized treatment. This review highlights recent discoveries in circulating melanoma biomarkers, explores the challenges and potentials of emerging technologies for liquid biomarker discovery, and discusses future directions in melanoma biomarker research. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is an aggressive type of skin cancer. This type of cancer is invasive but preventable and treatable if detected early. This article explores currently ongoing new trials in melanoma screening. Activities aimed at behavioural changes and health promotion are valuable tools to further reduce the burden of this disease. Background: The World Health Organisation reports that melanoma had an incidence of 331,722 cases worldwide in 2022, ranking it 17th on the list of the most prevalent malignancies. This disease is a threat to public health as years of potential life lost from melanoma deaths constitute an economic and social burden; it is, however, curable if detected early. This study aims to show current trends in clinical trials for melanoma screening. Materials and Methods: The analysis was conducted using data from clinicaltrials.gov. The analysis considered both interventional and observational studies on melanoma screening. Only the studies with complete and active statutes by 4 September 2024 were included in the analysis. Results: Out of 25 studies registered in clinical trial databases regarding melanoma screening, 20% research advanced imagining techniques employing innovative machine learning algorithms, while 16% explore behavioural interventions. Conclusions: Intensification of behavioural interventions and health promotion activities is recommended. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive neoplastic process of precursor plasmacytoid dendritic cells. The diagnostic evaluation of this heterogenous entity is challenging, requiring a comprehensive approach of incorporating clinical, morphologic, immunohistochemical, and molecular/cytogenetic evaluations. Optimal management of BPDCN remains controversial, and clinical outcomes continues to be poor. Pediatric cases of BPDCN are rare and to our knowledge, this is the second case of BPDCN described in a Hispanic child, first one was described outside the US in Peru. Here, we report a case of a juvenile patient of Hispanic origin presenting with cutaneous and bone marrow involvement and initially misdiagnosed as a cutaneous infection that resulted in subsequent delaying of necessary chemotherapy for 2 months. Biopsy of the lesion showed diffuse infiltration of immature cells involving the dermis with classical sparring of epidermis. A huge panel of immunohistochemical stains were performed to reach the diagnosis of BPDCN. Staging bone marrow biopsy also revealed involvement by BPDCN. Treatment was not only delayed in this patient but also due to the rarity of BPDCN in pediatric population, the subsequent therapeutic decisions were challenging for the primary oncology team as it was based solely on published literature on adult population. Our case report will not only add one more case in the pediatric age group, but also will also emphasize that although BPDCN has a grave prognosis in the elderly, timely diagnosis with prompt treatment is the key to complete remission in pediatric BPDCN population. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline injection-site sarcomas (FISSs) are malignant skin tumors of mesenchymal origin arising at local post-vaccination (or injection) sites due to the neoplastic transformation of fibroblasts and myofibroblasts. In recent years, a fluorescence imaging technique based on probes targeting αvβ3 integrin was effectively applied as optical guidance in the surgical complete resection of the tumor. In our study, we investigated the utility of a commercially available antibody directed against αv integrin for the histopathological evaluation of FISS's surgical excision margins. Although the antibody did not allow us to mark neoplastic cells over reactive ones in the biopsies, an interesting membranous positivity was found in multinucleated giant cells of the pleomorphic sarcoma variant of FISS, suggesting a specific role for αv integrin in the oncogenesis of this subtype of FISS. Feline injection-site sarcomas (FISSs) are malignant skin tumors of mesenchymal origin arising at local post-vaccination (or injection) sites. In recent years, a fluorescence imaging technique based on probes targeting αvβ3 integrin has been effectively applied for the surgical complete resection of the tumor. In our study, we investigated the utility of a commercially available anti-αv integrin polyclonal antibody for the histopathological evaluation of FISS's surgical excision margins. We collected 10 formalin-fixed paraffin-embedded (FFPE) feline excisional biopsies with a histopathological diagnosis of FISS (7 fibrosarcomas and 3 pleomorphic sarcomas) and wide margin tissue, along with one subcutaneous injection-site granuloma and 6 osteosarcomas. Samples were processed for histology, and slides were stained for IHC with the anti-αv integrin antibody. Immunostained slides were evaluated for the cellular localization and intensity of the staining in different neoplastic and non-neoplastic cell populations. Neoplastic and non-neoplastic spindle cells had cytoplasmic positivity in all fibrosarcomas. Inflammatory cells, including macrophages of the injection-site granuloma, were negative. Multinucleated giant cells in the pleomorphic sarcomas had an intense membranous positivity. Although the anti-αv integrin antibody was ineffective for the histopathological evaluation of surgical excision margins, the membranous localization of αv integrin in multinucleated giant cells of pleomorphic sarcomas suggests that it plays a role in the oncogenesis of this FISS variant. [ABSTRACT FROM AUTHOR]

Cutaneous malignant melanoma (MM) is the most aggressive form of skin cancer, associated with high mortality and rising incidence rates in Europe despite prevention efforts. Nodular MM, the most aggressive subtype, often mimics other skin tumors, complicating diagnosis. We present the case of a 66-year-old woman with a large, ulcerated tumor beneath the left scapula, along with multiple nodular lesions on the left arm and chest. Initially suspected to be an aggressive squamous cell carcinoma, the diagnosis was confirmed as invasive cutaneous MM with a BRAF(V600) mutation via biopsy. Staging with PET/CT revealed extensive glucose metabolism in the tumors and surrounding tissues, as well as metastatic lymphadenopathy. The disease was classified as stage IV (T4bN3cM1a0). Neoadjuvant systemic therapy with BRAF and MEK inhibitors (Dabrafenib and Trametinib) was initiated to reduce tumor size. Remarkable regression was observed within a week, with further reduction in tumor size after one month. A follow-up PET/CT after 3 months showed significant decreases in tracer uptake and lesion size, with a ΔSUVmax of 51.9%, a ΔMTV of 74.5%, and a ΔTLG of 83.5%, indicating an excellent response to targeted therapy. [ABSTRACT FROM AUTHOR]

Trichilemmal carcinoma is an extremely rare malignant cutaneous tumor derived from the outer root sheath of the hair follicles, which most commonly occurs in the sun-exposed areas of elderly individuals. This article introduces a case of trichilemmal carcinoma that occurred on the scalp of a 36-year-old male patient, the first case reported and treated with surgical excision combined with photodynamic therapy. [ABSTRACT FROM AUTHOR]

Endocrine mucin-producing sweat gland carcinoma is a rare neoplasm of the skin appendages. The tumor typically exhibits slow growth and rarely metastasizes to distant sites. Herein, we report a case of a 77-year-old male who presented with a skin lesion on the right anterior chest wall 23 years ago. Fifteen years later, surgical excision was performed, and the pathological diagnosis was endocrine mucin-producing sweat gland carcinomas. However, the histopathological examination revealed a coexistence of endocrine mucin-producing sweat gland carcinomas and mucinous carcinoma components. Over the past 2 years, the patient developed lymph node metastasis in the right axilla, local recurrence on the right chest wall, and distant skin metastasis. The histopathological type of the lymph node metastasis was consistent with the primary tumor, while the recurrent and skin metastatic lesions exhibited mucinous carcinoma. To our knowledge, this is the first reported case of endocrine mucin-producing sweat gland carcinoma with distant skin metastasis, characterized by two distinct carcinoma components in the histopathological morphology. [ABSTRACT FROM AUTHOR]

Simple Summary: Following surgery, dabrafenib and trametinib have been approved for the treatment of stage III melanoma with a B-RAF gene mutation. A retrospective–prospective observational trial conducted in Italy, known as MADAM (Maximizing ADjuvAnt MAP), included patients who had received at least one dose of trametinib plus dabrafenib. Following the first 24 months of follow-up, this analysis was the first. The trial involved 310 patients in total, of whom 240 completed the 12-month course of treatment, while 70 discontinued therapy. At 24 months, the majority of patients (80.2%) were alive and had not experienced disease relapse. The combination of trametinib and dabrafenib appears to benefit patients by lowering the rate of relapse. Background/Objective: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. Methods: The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective–prospective observational study that included patients who received at least one dose of D + T through the MAP. The primary endpoints were relapse-free survival (RFS) and overall survival (OS). Results: This interim analysis presents findings after the first 24 months of follow-up. A total of 310 patients were included in the study; 240 completed the 12-month treatment with D + T, while 70 discontinued the combination. RFS rates were 93.2% at 12 months and 80.2% at 24 months. The median RFS was not reached for the overall population or any subgroups. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. Conclusions: D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Simple Summary: Image-guided superficial radiation therapy (IGSRT) is an emerging treatment option for non-melanoma skin cancers (NMSCs). The aim of this retrospective cohort study was to assess if there are relationships between patient comorbidities or socioeconomic status (SES) and outcomes from IGSRT treatment for their NMSCs. Data from 19,988 NMSCs revealed no difference in freedom from recurrence in less vs. more deprived neighborhoods (as a measurement of SES) or in patients without comorbidities vs. with many and/or severe comorbidities. This supports the use of IGSRT regardless of SES or comorbidities. Background: Non-melanoma skin cancers (NMSCs) are the most common cancers in the United States. Image-guided superficial radiation therapy (IGSRT) is an effective treatment for NMSCs. Patient comorbidities and socioeconomic status (SES) are known contributors to health disparities. However, the impact of comorbidities or SES on the outcomes of IGSRT-treated NMSCs has not yet been studied. This study evaluated freedom from recurrence in IGSRT-treated NMSCs stratified by SES and the number of comorbidities. Methods: This large retrospective cohort study evaluated associations between SES (via Area Deprivation Index (ADI)) or comorbidity (via Charlson Comorbidity Index (CCI)) and 2-, 4-, and 6-year year freedom from recurrence in patients with IGSRT-treated NMSC (n = 19,988 lesions). Results: Freedom from recurrence in less (ADI ≤ 50) vs. more (ADI > 50) deprived neighborhoods was 99.47% vs. 99.61% at 6 years, respectively (p = 0.2). Freedom from recurrence in patients with a CCI of 0 (low comorbidity burden) vs. a CCI of ≥7 (high comorbidity burden) was 99.67% vs. 99.27% at 6 years, respectively (p = 0.9). Conclusions: This study demonstrates that there are no significant effects of SES or comorbidity burden on freedom from recurrence in patients with IGSRT-treated NMSC. This supports the expansion of IGSRT in deprived neighborhoods to increase access to care, and IGSRT should be a consideration even in patients with a complex comorbidity status. [ABSTRACT FROM AUTHOR]