Actinic Keratosis Research Articles

Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma insitu (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Combination of 5-fluorouracil with photodynamic therapy enhances immune responses in a murine model of actinic keratosis

SignificancePhotodynamic therapy (PDT) to treat actinic keratoses (AK) involves application of a photosensitizer followed by exposure to light, resulting in effective lesion clearance by inducing cell death and long-term immune responses. Here, we show that pretreatment of AK lesions with 5-fluorouracil (5FU) causes significant enhancement of PDT-related immune effects. ApproachSKH-1 mice with AK (generated by repeated UVB exposure) were treated topically with 5FU for three days prior to application of topical ALA followed by blue light exposure. AK lesions were harvested for time-course analyses of intra-tumoral immune responses after PDT with or without 5FU. ResultsImmunofluorescence data showed that 5FU pretreatment increased recruitment of innate immune cells, infiltration of activated T cells and of cytotoxic T cells and reduced the presence of cells expressing the immune checkpoint marker PD1. ConclusionsOur results suggest that a combination of 5FU and PDT may synergize to provide better management of AK in the dermatology clinic.

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Vitamin D in combination with photodynamic therapy enhances innate immune response in a murine model of actinic keratosis

SignificanceAminolevulinate-based photodynamic therapy (ALA-PDT) is an effective treatment for cutaneous pre-cancer (actinic keratoses; AK) and non-melanoma skin cancer (NMSC), the most common skin malignancies. ApproachIn this study we show that pretreatment of murine AK lesions with vitamin D (VitD), causes significant enhancement of PDT-related immune effects. Hairless (SKH-1) mice with AK (generated by repeated UVB exposure) were treated topically with VitD (Vectical™) for three days prior to application of topical ALA followed by blue light exposure. A time course analysis of immune cell infiltration in AK lesions was conducted by immunofluorescence (IF) microscopy after PDT with or without VitD. ResultsOur IF data showed significant differences between infiltration of innate immune cells (neutrophils, macrophages and dendritic cells) in vehicle versus VitD treated lesions. ConclusionsOur data indicate that a combination of VitD and PDT may have an additive beneficial effect on therapeutic outcome of PDT.

A continuous-wave spectroscopic singlet oxygen sensor for photodynamic therapy dosimetry: Preclinical studies in a murine model of actinic keratosis

SignificanceSinglet oxygen (1O2), a type of reactive oxygen species, destroys cancer cells during photodynamic therapy (PDT). Inter-patient variations in tissue oxygen levels, dose of photosensitizer (PS), and fluence of light can affect 1O2 generation and result in suboptimal treatment efficacy in the clinic. ApproachHere, we describe a high throughput spectrometer system based on computational spectroscopy for real-time measurement of PS levels and 1O2 luminescence during PDT. The dosimeter provides a direct real-time measurement of 1O2 production in continuous-wave mode. Data were obtained from in-vitro protoporphyrin IX (PpIX) phantoms, and from in-vivo studies in mice with actinic keratosis (AK, an early form of squamous cell carcinoma) using the dosimeter. ResultsData indicated a correlation between 1O2 levels and treatment outcome (lesion shrinkage/clearance). ConclusionsThis study provides additional evidence for a correlation between 1O2 generation and AK treatment response, suggesting that 1O2 dosimetry could have utility in the dermatology clinic.

Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

Sexual dimorphism of the increment rate of age-specific incidence of actinic keratoses: an observational, single-centre study.

Sexual dimorphism of the increment rate of age-specific incidence of actinic keratoses: an observational, single-centre study.

Treatment and follow-up of melanoma in situ in a geriatric patient that is a nonsurgical candidate

Background: The standard of care for melanoma in situ is a wide excision with at least 0.5 cm margins. These melanomas can be large in size, and some elderly patients are not good surgical candidates so alternative treatment options have been explored. Topical imiquimod is currently approved by the Federal Drug Administration for the treatment of actinic keratosis, external anogenital warts, and superficial basal cell carcinoma. In some patients, treatment with topical imiquimod for malignant melanoma in situ has been shown to be successful. Case report: A 97-year-old male patient presented to a dermatology office with a 4.5×4.0 cm malignant melanoma in situ. The patient was given treatment options of excision and radiation therapy but refused due to his advanced age and desire to avoid extensive surgery. The patient agreed to topical treatment with imiquimod cream 5 times weekly for 5 months. A post-treatment repeat biopsy showed no evidence of residual malignant melanoma in situ. Continued post-treatment follow-up at 3-month internals with pigmented lesion assay(s) and repeat biopsies showed no evidence of recurrence at 1 year. Conclusions: In geriatric patients with a large-sized melanoma in situ that are not good surgical candidates, treatment with topical imiquimod should be considered. Long-term follow-up with pigmented lesion assay(s) should be considered in these patients to help avoid biopsy fatigue, wound management, and complications from comorbidities.

Dermatoscopia del carcinoma epidermoide: de la queratosis actínica a las formas invasivas

When performing the dermoscopy of squamous cell carcinoma and its precursors we differentiate among keratin-related, vascular, and pigment-related criteria. Non-pigmented actinic keratoses are characterized by the “strawberry pattern”. Pigmented actinic keratosis shows a significant dermatoscopic overlap with lentigo maligna, but the presence of pigmented scales, erythema, and prominent follicles favors its diagnosis. Bowen's disease is characterized by clustered glomerular vessels, white-yellowish scales, and brown or grey dots arranged in lines in its pigmented variant. Finally, dermoscopy allows us to detect invasive squamous cell carcinoma in its early stages and differentiate it from its precursors. Furthermore, its presentation may vary depending on the degree of differentiation, with keratin-associated criteria predominating in well-differentiated tumors, while the atypical vascular pattern will predominate in poorly differentiated tumors.

SNC_Net: Skin Cancer Detection by Integrating Handcrafted and Deep Learning-Based Features Using Dermoscopy Images

The medical sciences are facing a major problem with the auto-detection of disease due to the fast growth in population density. Intelligent systems assist medical professionals in early disease detection and also help to provide consistent treatment that reduces the mortality rate. Skin cancer is considered to be the deadliest and most severe kind of cancer. Medical professionals utilize dermoscopy images to make a manual diagnosis of skin cancer. This method is labor-intensive and time-consuming and demands a considerable level of expertise. Automated detection methods are necessary for the early detection of skin cancer. The occurrence of hair and air bubbles in dermoscopic images affects the diagnosis of skin cancer. This research aims to classify eight different types of skin cancer, namely actinic keratosis (AKs), dermatofibroma (DFa), melanoma (MELa), basal cell carcinoma (BCCa), squamous cell carcinoma (SCCa), melanocytic nevus (MNi), vascular lesion (VASn), and benign keratosis (BKs). In this study, we propose SNC_Net, which integrates features derived from dermoscopic images through deep learning (DL) models and handcrafted (HC) feature extraction methods with the aim of improving the performance of the classifier. A convolutional neural network (CNN) is employed for classification. Dermoscopy images from the publicly accessible ISIC 2019 dataset for skin cancer detection is utilized to train and validate the model. The performance of the proposed model is compared with four baseline models, namely EfficientNetB0 (B1), MobileNetV2 (B2), DenseNet-121 (B3), and ResNet-101 (B4), and six state-of-the-art (SOTA) classifiers. With an accuracy of 97.81%, a precision of 98.31%, a recall of 97.89%, and an F1 score of 98.10%, the proposed model outperformed the SOTA classifiers as well as the four baseline models. Moreover, an Ablation study is also performed on the proposed method to validate its performance. The proposed method therefore assists dermatologists and other medical professionals in early skin cancer detection.

Pre-treatment with topical 5-fluorouracil increases the efficacy of daylight photodynamic therapy for actinic keratoses – A randomized controlled trial

BackgroundDaylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance.This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses. MethodsSixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight. ResultsTwelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments. ConclusionsSequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction.

Characterization of the skin microbiome in normal and cutaneous squamous cell carcinoma affected cats and dogs.

The progression of precancerous actinic keratosis lesions (AK) to cutaneous squamous cell carcinoma (SCC) is poorly understood in humans and companion animals, despite causing a significant burden of disease. Recent studies have revealed that the microbiota may play a significant role in disease progression. Staphylococcus aureus has been found in high abundance on AK and SCC lesions, where it secretes DNA-damaging toxins, which could potentiate tumorigenesis. Currently, a suitable animal model to investigate this relationship is lacking. Thus, we examined the microbiome of cutaneous SCC in pets, revealing similarities to humans, with increased staphylococci and reduced commensals on SCC lesions and peri-lesional skin compared to normal skin. Two genera that were in abundance in SCC samples have also been found in human oral SCC lesions. These findings suggest the potential suitability of pets as a model for studying microbiome-related skin cancer progression.

Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Abstract 761: The relationship between ANGPTL4 and epidermal malignant transformation

Abstract High body mass index (BMI) is a risk factor for several types of cancers. Although epidemiology suggests obesity is negatively associated with non-melanoma skin cancer (NMSC), bariatric surgery has been shown to reduce the risk, suggesting a possible role of adipose tissue in the initiation and promotion of skin cancer. To gain mechanistic insight into how adipose tissue drives cutaneous carcinogenesis, we cultured non-tumorigenic mouse keratinocytes (JB6 P+ cells) with or without factors released from murine visceral adipose tissue (mFTF) and performed RNA-Sequencing. Published work demonstrated mFTF induces anchorage-independent cell growth, a surrogate marker for malignant transformation. Transcriptomic analysis demonstrated a significant induction of Angptl4 mRNA in JB6 P+ cells cultured with mFTF for 3 and 8 hours compared to the vehicle-treated cells. ANGPTL4 is an endogenous inhibitor of lipoprotein lipase that modulates free fatty acid delivery to adipose tissue and oxidative tissues such as muscle and liver. The C-terminal protein demonstrates tumor-associated activities such as angiogenesis, metastasis, protection against anoikis, and enhancement of cell survival. Therefore, we hypothesized that the induction of this gene promotes malignant transformation. RNA-seq data was validated in multiple cell models, including primary keratinocytes with human adipose tissue. Immunohistochemistry was used to assess ANGPTL4 expression in 37 actinic keratosis (pre-malignant) and cutaneous squamous cell carcinoma (cSCC) from patients with different BMIs (18.6 - 49.5). Notably, ANGPTL4 was only observed in the suprabasal epidermal layers in normal skin. For samples containing both lesional and perilesional skin, there was an increase in ANGPTL4 expression in the lesional epidermis relative to the normal perilesional skin. Furthermore, ANGPTL4 expression increased from transition to actinic keratosis to cSCC in situ, suggesting that ANGTL4 is induced during malignant transformation as observed in our pre-clinical models. Interestingly, once cSCC developed an invasive component, ANGTPL4 expression was lost in the invasive keratinocytes but persisted in the in situ component. There was no association between ANGPTL4 expression and BMI in lesional tissue. These data suggest that targeting ANTPLT4 may be a novel therapy for the prevention of skin cancer and that ANGPTL4-high patients or cancer patients with obesity may be a critical demographic for potential risk assessment or therapeutic intervention. Future studies will determine the impact of knocking out ANGTPL4 in our models of malignant transformation. Citation Format: Nat Ato Yawson, Jonathan D. Diedrich, Karen T. Liby, Jesse Veenstra, Jamie Jenna Bernard. The relationship between ANGPTL4 and epidermal malignant transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 761.

Early Results of a Screening Program for Skin Cancer in Liver Transplant Recipients: A Cohort Study.

(1) Background: Skin cancer is the most common cancer in transplant recipients. Timely and regular screening may reduce advanced disease. The study aimed to determine referral rates to screening, the incidence, and risk factors of skin cancer in a Danish liver transplant recipient cohort. (2) Methods: All first-time liver transplant recipients, >18 years old, attending outpatient care between January 2018 and December 2021 were included. The referral rates and incidence of skin cancer/preneoplastic lesions were calculated. Risk factors were assessed using Cox regression analyses. (3) Results: Of the 246 included recipients, 219 (89.0%) were referred to screening, and 102 skin cancer/preneoplastic lesions were diagnosed in 32 (15.6%) recipients. The IR of any skin cancer/preneoplastic lesion was 103.2 per 1000 person-years. BCC was the most frequent skin cancer followed by SCC, IR: 51.3 vs. 27.1 per 1000 person-years, respectively. No cases of MM were observed. The IR of actinic keratosis and Bowen's Disease were 48.1 vs. 13.2 per 1000 person-years, respectively. Time since transplantation was independently associated with skin cancer/preneoplastic lesions, HR (95%CI) 2.81 (1.64-4.80). (4) Conclusions: The study determined the incidence and risk factors of skin cancer/preneoplastic lesions in liver transplant recipients enrolled in a screening program, while demonstrating a high screening referral rate.

Advancements in elucidating the pathogenesis of actinic keratosis: present state and future prospects.

Solar keratosis, also known as actinic keratosis (AK), is becoming increasingly prevalent. It is a benign tumor that develops in the epidermis. Individuals with AK typically exhibit irregular, red, scaly bumps or patches as a result of prolonged exposure to UV rays. These growths primarily appear on sun-exposed areas of the skin such as the face, scalp, and hands. Presently, dermatologists are actively studying AK due to its rising incidence rate in the United States. However, the underlying causes of AK remain poorly understood. Previous research has indicated that the onset of AK involves various mechanisms including UV ray-induced inflammation, oxidative stress, complex mutagenesis, resulting immunosuppression, inhibited apoptosis, dysregulated cell cycle, altered cell proliferation, tissue remodeling, and human papillomavirus (HPV) infection. AK can develop in three ways: spontaneous regression, persistence, or progression into invasive cutaneous squamous cell carcinoma (cSCC). Multiple risk factors and diverse signaling pathways collectively contribute to its complex pathogenesis. To mitigate the risk of cancerous changes associated with long-term UV radiation exposure, prompt identification, management, and prevention of AK are crucial. The objective of this review is to elucidate the primary mechanisms underlying AK malignancy and identify potential treatment targets for dermatologists in clinical settings.

Assessing field cancerization and actinic keratosis using ultraviolet-induced fluorescence dermatoscopy after the application of 5-aminolevulinic acid – An observational study

BackgroundActinic keratoses (AK) are one of the most frequent reasons for consultations in dermatology. Ultraviolet-induced fluorescence dermatoscopy (UVFD) is a new method that allows the assessment of lesions in a spectrum of light that originates from the fluorochromes emitting UV-excited luminescence. The aim of this study was to assess the UVFD features of AKs before PDT and their intensity in field cancerization and single lesions. MethodsThis retrospective study was conducted from June to November 2023. Lesions were assessed with the Olsen scale clinically and dermatoscopically (DermLite DL5, 10x magnification) and photographed. UVFD fluorescence was categorized as ‘none’, ‘weak’, ‘moderate’, and ‘intense’. A 1-mm thick layer of 10 % 5-ALA gel was applied to single lesions or cancerization field (depending on the patient) and covered with an occlusive dressing for 3 h. Prior the application of 10 % 5-ALA gel, the lesions were degreased with an alcoholic solution. The occlusion was removed, and the field was cleaned with a 0,9 % saline solution. Afterward, each lesion was photographed in polarized light and UVFD mode. ResultsA total of 194 dermatoscopic images were analyzed, 111 corresponded to field cancerization and 81 to single AKs. Overall, weak fluorescence was noticed in 22 of them (11,3 %), moderate in 107 (55,15 %), and intense in 65 (33,5 %). Amongst field cancerization (111 images), weak fluorescence was seen in 11 (9.9 %), moderate in 68 (61,26 %), and intense in 32 (28,82 %). In single lesions (81 images), weak fluorescence was detected in 11 (13,2 %), moderate in 39 (46,99 %), and intense in 33 (28.83 %) of the lesions. Slightly more intense fluorescence was noticed in higher Olsen grade (p = 0.04). ConclusionsUVFD can enhance our efficacy of pre-procedural examination and might arise as a useful device to predict the therapeutic effect of PDT.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis

BackgroundConventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies. ObjectiveTo compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. MethodsWe conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a “blinded” investigator. ResultsLesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas. ConclusionThe occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.

Spectrum of malignant and premalignant skin lesions in 505 adult subjects at risk of skin cancers

Patients at risk of skin cancers can develop varying types of cutaneous malignancies. However, some subjects may develop only one type of lesion. In this cross-sectional study, the spectrum of premalignant (PM) and malignant skin lesions and their risk factors were studied. Therefore, 505 adult subjects (aged 21–79 years, 256 males and 249 females, 96 with immunosuppression) at risk of any type of skin cancer were examined for cutaneous malignancies, nevi, actinic keratoses, photodamage, and possible risk factors. First, 12 different groups were identified with a varying set of PM and/or malignant skin lesions. Next, 5 larger groups were formed from them: basal cell carcinoma (BCC) only, malignant melanoma (MM) only, squamous cell carcinoma (SCC) and/or PM, BCC + SCC and/or PM, and MM + keratinocyte carcinoma (KC) and/or PM. The groups with BCC or MM only were younger and showed less photodamage than the mixed groups, while SCC/PM showed similarity with them. In logistic regression analyses, the platelet-to-lymphocyte ratio was associated with an increased risk of concomitant KC (OR 1.028, p = 0.023) or SCC/PM (OR 1.009, p = 0.047) in subjects with MM or BCC, respectively. Actinic keratoses produced ORs 0.246–0.252 (p = 0.008–0.020) for BCC in subjects with SCC/PM. Interestingly, atypical mole syndrome decreased the risk of SCC/PM in subjects with BCC (OR 0.092, p = 0.001). Advanced age was a significant risk factor for an additional type of lesion in all 3 comparisons (ORs 1.088–1.388, p = 0.001). In conclusion, even though there are numerous patients with only one lesion type, advancing age may determine the final lesion multiplicity.

Topical Immunotherapy for Actinic Keratosis and Field Cancerization.

This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.