Keratinocyte Carcinoma Research Articles

Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study

BackgroundChildhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. ObjectiveIdentify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. MethodsKC were identified among Childhood Cancer Survivor Study participants, a cohort of five-year cancer survivors diagnosed <21 years of age between 1970-1999 in North America. Cumulative incidence was estimated, and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. ResultsAmong 25,658 participants, 1,446 developed 5,363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy [RT]). Mean lesion count was 3.7 with 26.1% experiencing ≥4. RT imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LimitationsParticipant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. ConclusionsThe burden of KC in CCS remains high, but predictable risk factors should guide screening

Incidence and outcomes of Merkel cell carcinoma related to Merkel cell polyomavirus status in Iceland in 1981-2023

BackgroundImpact of Merkel cell polyomavirus (MCPyV) associated Merkel cell carcinoma (MCC) has not been assessed in the Icelandic population, nor in a whole population elsewhere. ObjectivesThe primary objective was to assess trends in the incidence of MCC in Iceland and the association with MCPyV. Secondary objectives aimed to analyze MCC outcomes. MethodsIn this retrospective cohort study, patients diagnosed with MCC between 1981 and 2021 were identified from the Icelandic Cancer Registry. Patients were separated into two groups based on MCPyV immunochemistry staining. Age-standardized incidence was calculated and Joinpoint analysis was used to assess incidence trends. A Cox proportional hazards model was used to assess survival differences between the two groups. ResultsOverall incidence of MCC increased from 0.015 to 0.26 per 100,000 persons, though the incidence of MCPyV positive cases recently decreased while negative cases increased. MCPyV negative tumors were associated with sun exposure (p<0.01), a history of keratinocyte carcinoma, smaller tumor size, and lower overall survival. LimitationsEven with population level data, comprehensively investigating associations with MCC is difficult due to its rarity. ConclusionMCPyV negative MCC tumors were associated with lower survival despite smaller tumor size. Thus, MCPyV status could be an important prognostic biomarker.

Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. Apply the authors' classification system within a validation cohort. Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

Cost-of-Illness of Skin Cancer: A Systematic Review.

Skin cancer's rising incidence demands understanding of its economic impact. The current understanding is fragmented because of the various methodological approaches applied in skin cancer cost-of-illness studies. This study systematically reviews melanoma and keratinocyte carcinoma cost-of-illness studies to provide an overview of the applied methodological approaches and to identify the main cost drivers. This systematic review was conducted adhering to the 2020 PRISMA guidelines. PubMed, Embase, and Web of Science were searched from December 2022 until December 2023 using a search strategy with entry terms related to the concepts of skin cancer and cost of illness. The records were screened on the basis of the title and abstract and subsequently on full text against predetermined eligibility criteria. Articles published before 2012 were excluded. A nine-item checklist adapted for cost-of-illness studies was used to assess the methodological quality of the articles. This review included a total of 45 studies, together evaluating more than half a million patients. The majority of the studies (n = 36) focused on melanoma skin cancer, a few (n = 3) focused on keratinocyte carcinomas, and 6 studies examined both. Direct costs were estimated in all studies, while indirect costs were only estimated in nine studies. Considerable heterogeneity was observed across studies, mainly owing to disparities in study population, methodological approaches, included cost categories, and differences in healthcare systems. In melanoma skin cancer, both direct and indirect costs increased with progressing tumor stage. In advanced stage melanoma, systemic therapy emerged as the main cost driver. In contrast, for keratinocyte carcinoma no obvious cost drivers were identified. A homogeneous skin cancer cost-of-illness study design would be beneficial to enhance between-studies comparability, identification of cost drivers, and support evidence-based decision-making for skin cancer.

Cutaneotropic polyomavirus abundance in the nonlesional skin of keratinocyte carcinoma patients: A cross-sectional study

Cutaneotropic polyomavirus abundance in the nonlesional skin of keratinocyte carcinoma patients: A cross-sectional study

P072 Risk of incident cancer, excluding keratinocyte carcinoma, in patients with psoriasis treated with biologic therapy: a prospective cohort study from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), on behalf of the BADBIR Study Group

P072 Risk of incident cancer, excluding keratinocyte carcinoma, in patients with psoriasis treated with biologic therapy: a prospective cohort study from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), on behalf of the BADBIR Study Group

O05 Risk of keratinocyte carcinomas in patients with psoriasis treated with biologic therapy: analysis from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), on behalf of the BADBIR Study Group

O05 Risk of keratinocyte carcinomas in patients with psoriasis treated with biologic therapy: analysis from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), on behalf of the BADBIR Study Group

Genetically predicted TWEAK mediates the association between lipidome and Keratinocyte Carcinomas.

Reports suggest that lipid profiles may be linked to the likelihood of developing skin cancer, yet the exact causal relationship is still unknown. This study aimed to examine the connection between lipidome and skin cancers, as well as investigate any possible mediators. A two-sample Mendelian randomization (MR) analysis was conducted on 179 lipidomes and each skin cancer based on a genome-wide association study (GWAS), including melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Then, Bayesian weighted MR was performed to verify the analysis results of two-sample MR. Moreover, a two-step MR was employed to investigate the impact of TNF-like weak inducer of apoptosis (TWEAK)-mediated lipidome on skin cancer rates. MR analysis identified higher genetically predicted phosphatidylcholine (PC) (17:0_18:2) could reduce the risk of skin tumors, including BCC (OR=0.9149, 95% CI: 0.8667-0.9658), SCC (OR=0.9343, 95% CI: 0.9087-0.9606) and melanoma (OR=0.9982, 95% CI: 0.9966-0.9997). The proportion of PC (17:0_18:2) predicted by TWEAK-mediated genetic prediction was 6.6 % in BCC and 7.6% in SCC. The causal relationship between PC (17:0_18:2) and melanoma was not mediated by TWEAK. This study identified a negative causal relationship between PC (17:0_18:2) and keratinocyte carcinomas, a small part of which was mediated by TWEAK, and most of the remaining mediating factors are still unclear. Further research on other risk factors is needed in the future.

Incidence and geographic differences in keratinocyte carcinoma and Bowen's disease in office‐based dermatological practice between 2013 and 2022: A nationwide Danish registry‐based study

AbstractBackgroundRates of keratinocyte carcinoma (KC) across Europe are impacted by population demographics and geography. Regional differences in KC occurrence exist, but few European studies investigate incidences of specific subtypes in the secondary healthcare sector on a national level.ObjectivesTo determine geographical differences in incidence rate and lifetime risk of KC subtypes across Denmark, including nodular and superficial basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen's disease (BD), identified in office‐based dermatological practice.MethodsBased on a nationwide registry (The Danish Skin Cancer Registry), all patients in Denmark's five regions with a histologically‐ or clinically verified KC or BD registered in a state‐funded office‐based dermatology practice between 2013 and 2022 were included. Trends in national‐ and region‐specific age and sex standardised tumour incidence rates (STIR) were calculated. Further, national lifetime risk of each tumour subtype was estimated.ResultsBetween 2013 and 2022, the combined STIR for KC/BD rose 172% nationally from 180 to 489 per 100,000 person‐years (PY). This increase reflected rising rates of nodular BCC, SCC, and BD, while superficial BCC incidence was relatively stable. Regional differences in STIR for combined KC/BD were observed, with the Capital Region and North Jutland generally demonstrating higher rates than Zealand, Southern‐ and Central Denmark (e.g., North Jutland vs. Southern Denmark: 714 vs. 405/100,000PY). While the estimated lifetime risk of developing at least one KC or BD tumour was 21.8%, risk varied with tumour subtype, resulting in subtype‐specific risks of 16.4%, 5.1%, 1.9% and 1.3% for nodular BCC, superficial BCC, SCC, and BD, respectively.ConclusionsIn Denmark's secondary dermatological care sector, incidence of nodular BCC, SCC and BD continues to rise with an overall lifetime risk nearing 22%. While KC incidence is increasing in Denmark, the study detected differences in geographical trends and rate increases of specific tumour subtypes.

Cutaneous squamous cell carcinoma characterized by MALDI mass spectrometry imaging in combination with machine learning

Cutaneous squamous cell carcinoma (SCC) is an increasingly prevalent global health concern. Current diagnostic and surgical methods are reliable, but they require considerable resources and do not provide metabolomic insight. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) enables detailed, spatially resolved metabolomic analysis of tissue samples. Integrated with machine learning, MALDI-MSI could yield detailed information pertaining to the metabolic alterations characteristic for SCC. These insights have the potential to enhance SCC diagnosis and therapy, improving patient outcomes while tackling the growing disease burden. This study employs MALDI-MSI data, labelled according to histology, to train a supervised machine learning model (logistic regression) for the recognition and delineation of SCC. The model, based on data acquired from discrete tumor sections (n = 25) from a mouse model of SCC, achieved a predictive accuracy of 92.3% during cross-validation on the labelled data. A pathologist unacquainted with the dataset and tasked with evaluating the predictive power of the model in the unlabelled regions, agreed with the model prediction for over 99% of the tissue areas. These findings highlight the potential value of integrating MALDI-MSI with machine learning to characterize and delineate SCC, suggesting a promising direction for the advancement of mass spectrometry techniques in the clinical diagnosis of SCC and related keratinocyte carcinomas.

The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations

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

Artificial Intelligence in Dermatology: A Systematic Review of Its Applications in Melanoma and Keratinocyte Carcinoma Diagnosis.

Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps. The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC). Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023. Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.

Postinflammatory Hyperpigmentation Following Mohs Micrographic Surgery: An Observational Study.

Functional and cosmetic outcomes following Mohs micrographic surgery (MMS) are poorly studied in individuals with skin of color (SOC). Postinflammatory hyperpigmentation (PIH) may be long-lasting and highly distressing. SOC individuals are particularly susceptible to PIH following procedures.&nbsp; Objective: To characterize factors that contribute to the development of PIH following MMS in SOC. This retrospective study included 72 SOC individuals with 83 cases of keratinocyte carcinoma treated with MMS between August 2020 and August 2021 at a single medical center in the Bronx, New York. Postinflammatory hyperpigmentation following Mohs micrographic surgery was more common in Fitzpatrick skin types (FST) IV to V (48.0%) compared to FST I to III (18.2%; P=0.006). Grafts and granulation resulted in higher rates of PIH compared to linear repairs and flaps (87.5% vs 30.7%; P=0.003). Cases with postoperative complications resulted in higher rates of PIH compared to cases without (81.8% vs 29.2%; P=0.001). In a subset analysis of linear repairs, polyglactin 910 as a subcutaneous suture produced a higher rate of PIH compared to poliglecaprone 25 (46.2% vs 7.1%; P=0.015).&nbsp; Conclusions and Relevance: Individuals with SOC (FST IV to V) are more likely to develop PIH following MMS. Grafts and granulation lead to PIH more often than linear repairs and flaps. Postoperative complications significantly increase the risk of PIH. Surgeons should consider these risk factors during surgical planning in an effort to mitigate PIH in SOC individuals. Studies with larger sample sizes are indicated.&nbsp; J Drugs Dermatol. 2024;23(5):316-321. doi:10.36849/JDD.8146.

An overview of cutaneous squamous cell carcinoma imaging diagnosis methods.

Cutaneous squamous cell carcinoma, a type of non-melanoma skin cancer, is a form of keratinocyte carcinoma that stands as one of the most prevalent cancers, exhibiting a rising frequency. This review provides an overview of the latest literature on imaging methods for diagnosing squamous cell carcinoma (SCC) and actinic keratosis (AK). It discusses the diagnostic criteria, advantages, and disadvantages of various techniques such as dermatoscopy, skin ultrasound (US), in vivo and ex-vivo reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT). These methods offer benefits including non-invasiveness, rapidity, comprehensive lesion imaging, and enhanced sensitivity, but face challenges like high costs and the need for specialized expertise. Despite obstacles, the use of these innovative techniques is expected to increase with ongoing technological advancements, improving diagnosis and treatment planning for keratinocyte carcinomas. Standardizing LC-OCT imaging algorithms for AK, Bowen's disease, and SCC remains an area for further research.

A report on the safety of acitretin use in patients with renal failure on haemodialysis.

Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end-stage renal disease (ESRD) on haemodialysis (HD). However, these patients often lack medication choices and in certain clinical scenarios the benefits of acitretin may outweigh the potential risks. We identified 24 patients with ESRD on HD undergoing acitretin treatment from the Duke and Vanderbilt University Medical Centers. While adverse effects were common, they were not a frequent cause of treatment discontinuation among patients. We also found no association between acitretin treatment and hospital admissions or mortality. Lastly, we found statistically significant increases in alkaline phosphatase (ALP; P = 0.03) and total bilirubin (P < 0.001) when patients were receiving acitretin and HD compared with baseline. However, there was no dose dependency or temporal association with acitretin or HD initiation. Based on these preliminary findings, we find that acitretin may safely be used in patients receiving HD, with close monitoring of ALP and bilirubin.

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.

Abstract 279: Iatrogenic immunosuppression emplaces tacrolimus to drive squamous skin cancer progression and influence the microenvironment

Abstract One in thirteen organ transplant recipients (OTRs) develop post-transplant cutaneous squamous cell carcinoma (cSCC), leading to significant morbidity upon disease progression. Although chronic ultraviolet (UV) exposure primarily underlies keratinocyte carcinogenesis, long-term immunosuppression is a critical etiologic risk factor due to reduced systemic surveillance of dysplasia. Calcineurin inhibitors such as tacrolimus are commonly administered to suppress the immune system by blocking T-cell proliferation and preventing donor organ rejection. Contrarily, studies have evinced the off-target effects of immunosuppressives, namely azathioprine and cyclosporine, but not tacrolimus — the most widely used in all immunosuppression. In addition, the preclinical research literature has overlooked the contribution of stromal fibroblasts in the cSCC tumor microenvironment (TME). Hence, we hypothesize that tacrolimus exerts direct carcinogenic effects on keratinocytes and fibroblasts in the skin. We further postulate that tacrolimus enables a tumor-permissive microenvironment by activating dermal fibroblasts to cause aggressive and invasive keratinocyte carcinoma in OTRs. To examine this cellular crosstalk phenomenon, we used human keratinocytes, primary dermal fibroblasts and cSCC cells in mono- and co-cultures to mimic cutaneous and tumor complexities. Next, we assessed the molecular mechanisms utilized by tacrolimus to potentiate tumorigenesis pertinent to cell survival, proliferation and invasion. Herein, we show that tacrolimus promotes cell survival dose-dependently in cSCC cells. We also found that a fibroblast-cSCC spheroid co-culture significantly enhances cell invasion. In a wound-healing migration assay, tacrolimus increased the migratory capacity of normal keratinocytes and cSCC cells. However, cell proliferation remains nebulous due to cyclical dose-response effects in vitro. We then queried whether cell proliferation is affected in vivo using immunodeficient mice, and similar results were observed. We confirmed via immunoblotting that tacrolimus induced elevated expression of proliferation markers at distinct drug concentrations. Altogether, our findings illuminate keratinocyte-stroma interactions and particularly isolate the contributory role of tacrolimus in non-immune mediated cSCC pathogenesis. This knowledge suggests newer immunosuppressives that do not inhibit calcineurin activity may help relieve cutaneous malignancies in transplant recipients. Citation Format: Edwin Kumah, Yash Chhabra, Vania Wang, Agrani Dixit, Ashani Weeraratna, Kristin Bibee. Iatrogenic immunosuppression emplaces tacrolimus to drive squamous skin cancer progression and influence the microenvironment [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 279.

Effects of COVID-19 Pandemic on the Diagnosis of Melanoma and Keratinocyte Carcinomas: a Systematic Review and Meta-analysis.

Since December 2019, the COVID-19 pandemic has profoundly affected healthcare. The real effects of the COVID-19 pandemic on skin cancer are still unclear, more than 3 years later. This study aims to summarise the pandemic's impact on skin cancer diagnosis and outcome. A systematic review and meta-analysis was conducted, selecting studies comparing skin cancer diagnosis and prognosis post-pandemic with pre-pandemic data. A total of 27 papers were reviewed including 102,263 melanomas and 271,483 keratinocyte carcinomas. During the initial pandemic months (January-July 2020), melanoma surgeries dropped by 29.7% and keratinocyte carcinomas surgeries by 50.8%. Early pandemic tumours exhibited greater thickness and stage. In a long-term period beyond the initial months, melanoma surgeries decreased by 9.3%, keratinocyte carcinomas by 16.6%. No significant differences were observed in the Breslow thickness of melanomas after the start of the pandemic (mean difference 0.06, 95% confidence interval -0.46, 0.58). Melanomas operated on post-pandemic onset had an increased risk of ulceration (odds ratio 1.35, 95% confidence interval 1.22-1.50). Keratinocyte carcinomas showed increased thickness and worsened stage post-pandemic. However, studies included were mostly retrospective and cross-sectional, reporting diverse data. This review indicates that the pandemic likely caused delays in skin cancer diagnosis and treatment, potentially impacting patient outcomes.

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.

Viscum Album Lipophilic Extract in Actinic Keratosis, Cutaneous Squamous Cell Carcinoma, and Basal Cell Carcinoma: A Retrospective Case Series

Introduction: Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) belong to the group of keratinocyte carcinomas (KC). Actinic keratosis (AK) is a precursor lesion of cSCC. The incidences of cSCC, BCC, and AK are currently strongly increasing. Different standard therapies exist for these conditions but are not always applicable or successful. Hydrophilic Viscum album extracts have been used in anthroposophic cancer therapy since 1917. Viscum album lipophilic extract (VALE) is prepared by means of supercritical CO2 extraction. This retrospective case series assessed the safety and clinical effects of a topical application of 10% VALE in individual cases of cSCC, BCC, and AK. Methods: For this retrospective case series, a positive vote was obtained from the Ethics Committee of the University of Witten/Herdecke (No. 146/2020). Eligible patients signed a declaration of consent prior to inclusion in the study. The main outcome parameters were the clinical response to treatment with VALE and adverse drug reactions. Risk factors, concomitant therapies and diseases, further diagnostic and therapeutic information were documented where available. Data analysis was performed on the level of patients and of individual lesions. Results: The study population consisted of 55 patients with 74 skin lesions. Individual case analysis accompanied by photographic documentation revealed typical and promising treatment courses. Clinical response rates (complete + partial remissions) for individual lesions were 78% for cSCC, 70% for BCC, and 71% for AK. Complete remission rates for individual lesions were 56% for cSCC, 35% for BCC, and 15% for AK. In cSCC and BCC, shorter times to best clinical response were observed. Adverse drug reactions were reported in 5 patients including erythema and inflammatory reactions of mostly moderate severity that resolved completely. In one case, therapy was temporarily paused, in four cases it was continued without interruption. Discussion/Conclusion: The results of this study suggest that VALE is a safe and tolerable extract under whose application complete and partial remissions of KC could be observed. To improve and assess the efficacy of VALE, prospective investigations are necessary.