Basal Cell Carcinoma Of Skin Research Articles

Transcriptomic Analysis of Early-Stage Basal Cell Carcinomas in Murine Skin Following Topical Treatments With Ablative Fractional Laser and Vismodegib.

Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterise the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of topical application of the hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation (significantly upregulated genes: 277, significantly downregulated genes: 24). Characterisation of these genes with Ingenuity Pathway Analysis showed that tumour induction was associated with activation of BCC and Sonic Hedgehog signalling. Both AFL and vismodegib treatments reversed these changes, with vismodegib demonstrating superior performance by reversing most of the upregulated genes (AFL: 59/277; vismodegib: 180/277). Surprisingly, Ingenuity Pathway Analysis also revealed that both AFL and vismodegib treatments caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment suggest key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining the effect of AFL on the immune system with other topical treatments.

A case of basal cell carcinoma of skin with bone metastasis: a case report

BackgroundBasal cell carcinoma is the most prevalent skin cancer, most characterized by local aggressiveness but with low metastatic potential, and bone metastasis is quite heterogeneous, thus the incidence profile is variable size from 0.0028% to 0.5%. We have this patient with an unusual example of basal cell carcinoma with bone metastases to add to the scarce report on this matter.Case descriptionHere we document a 48-year-old Persian man with a background of being exposed to the sun for a long time. He was diagnosed with an ulcer on the cheek, which was clinically characterized and further confirmed by biopsy as morpheaform basal cell carcinoma. Following the first round of excision, multiple relapses eventually metastasized to the bone. The latter was found on follow-up radiologic scans. This case is characterized by the aggressive nature of the disease and the heterogeneity of basal cell carcinoma growth, thus challenging the conventional view of basal cell carcinoma behavior. Treatment included surgical excision of the primary lesion, which was treated with radiotherapy afterward. However, the skeleton improved slowly during follow-up, and palliative care was eventually pursued to control symptoms and improve quality of life.ConclusionsThis was a rare case of basal cell carcinoma metastasis to non-bone organs, which reminded us to consider basal cell carcinoma metastasis, especially in the case of atypical basal cell carcinoma. Therefore, risk-aware patient management is essential. Moreover, these findings highlight the role of further research into the mechanisms of basal cell carcinoma metastasis, leading to improved therapeutic strategies that may lead to potential improvements in patient outcomes.

Contribution of Keratinocytes in Skin Cancer Initiation and Progression.

Keratinocytes are major cellular components of the skin and are strongly involved in its homeostasis. Oncogenic events, starting mainly from excessive sun exposure, lead to the dysregulation of their proliferation and differentiation programs and promote the initiation and progression of non-melanoma skin cancers (NMSCs). Primary melanomas, which originate from melanocytes, initiate and develop in close interaction with keratinocytes, whose role in melanoma initiation, progression, and immune escape is currently being explored. Recent studies highlighted, in particular, unexpected modes of communication between melanocytic cells and keratinocytes, which may be of interest as sources of new biomarkers in melanomagenesis or potential therapeutic targets. This review aims at reporting the various contributions of keratinocytes in skin basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, with a greater focus on the latter in order to highlight some recent breakthrough findings. The readers are referred to recent reviews when contextual information is needed.

RWHO: A hybrid of CNN architecture and optimization algorithm to predict basal cell carcinoma skin cancer in dermoscopic images

Basal cell carcinoma (BCC) is a type of skin cancer that initiates from the epithelial cells of our skin. Compared to other forms of cancer, BCC infrequently spreads to other parts of the body. It has a risk of local attack and demolition of surrounding tissues. Typically, BCC shows as one or numerous small, glowing nodules exhibiting central depressions. These knots are commonly found on the sun-exposed skin areas of older adults. Many dermatoscopic methods are available for diagnosing and predicting such kinds of skin cancers. But, medical professionals find it difficult to diagnose at some kind of images at the early stages. An automated methodology to predict such types of skin lesions would be better for such a diagnosis. In the present work, a new computer-assisted algorithm called RESNET50-WHO (RWHO) has been introduced to predict and diagnose BCC skin cancer. The method uses a combination of deep learning algorithm RESNET 50 and a metaheuristic algorithm, called wildebeest herd optimization (WHO) Algorithm to do prediction. The initial features from the images are extracted using RESNET 50. The output is given to the WHO algorithm to extract the beneficial features to reduce the time complexity. The method is tested using the PH2 dataset. The results obtained using the proposed algorithm is compared with the state-of-art optimization algorithms and evaluated. The conclusive findings specify that the proposed algorithm beats the comparative methods, yielding superior results

Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Occupational papillary thyroid carcinoma and basal cell carcinoma coexistence: a case report

Occupational cancers are cancers that result from exposure to carcinogens at work. Diagnosing occupational cancer expresses great importance in terms of public health. Because all occupational cancers are preventable as other occupational diseases. A detailed occupational history and careful questioning of exposure factors enable early diagnosis and prevention of occupational cancer. It is known that thyroid and skin cancers may occur due to occupational exposures. In this report, the coexistence of occupational thyroid cancer and occupational basal cell skin carcinoma is presented.

MSH3-related adenomatous polyposis in a patient with the negative family history of colorectal polyps

Recently, biallelic MSH3 germline pathogenic/likely pathogenic variants have been recognized as a rare cause of adenomatous polyposis. We present a 49-year-old woman who was admitted to our high-risk colorectal cancer clinic after incidental detection of a biallelic MSH3 (likely) pathogenic variant when tested for the germline (likely) pathogenic variants in hereditary breast and ovarian cancer related genes. The focus of this case report is to describe the genotype and phenotype of our patient with MSH3-related adenomatous polyposis. More than half of the polyps (13/19) were located in the right colon. In addition, benign and malignant extraintestinal lesions may be common as our patient had simple liver and kidney cysts and two basal cell skin carcinomas.

The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas

Cancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.

Initial clinical manifestations and early diagnosis of basal cell skin carcinoma

Background/Aim: Basal cell carcinoma (BCC) is the most common cancer of the skin. It is believed that increased UV radiation from the sun accounts for almost 90 % of the risk of BCC. There is a growing trend in the incidence of BCC in a younger population. The aim of study was to analyse the initial clinical symptoms of BCC that may be important for the early detection of this skin tumour. Method: The study was a prospective, multicentre study performed in the period from March 2017 to February 2022. A total of 69 respondents with BCC were analysed. Respondents applied for a targeted examination to examine a suspicious skin lesion (due to certain symptoms) or were diagnosed with BCC by accident, when examining other skin changes. Respondents were divided into 2 groups. The first, Group I (35 respondents), consisted of respondents with nodular BCC. The second, Group II (34 respondents), consisted of respondents with superficial spreading BCC. Initially, a careful history and data on the characteristics, shape and character of the tumour were taken from all respondents. Data on all (even the smallest) initial symptoms and relevant signs of evolution, as well as subjective problems related to the tumour were noted. All respondents underwent dermoscopy of suspected skin changes. Results: A significant difference was found between the examined groups in the characteristics of bleeding, crust formation and tendency to injury in lesions, where they occur more often in patients with nodular BCC. Symptoms such as burning and flaking occurred significantly more often in patients with superficial spreading BCC (p < 0.01), as well as the diameter of lesions over 5 mm (p < 0.05). Conclusion: Early clinical diagnosis of BCC is possible with a tumour diameter of only a few mm. The predominant initial (highly susceptible) symptoms of nodular BCC were initial bleeding and / or scab formation on the lesions, as well as propensity to injury. The superficial spreading form of BCC was often larger than 5 mm in diameter, with more frequent scaling of the lesion, as well as burning and stinging sensations in the tumour area. Itching was observed to be a very common previous occurrence in the BCC initial focus zone in subjects of both study groups. Dermsocopy is a highly reliable diagnostic method for early detection of BCC.

Structural and Functional Analysis of Crucial Protein Complex in Basal Cell Skin Carcinoma via Network Construction

 Background: The basal-cell carcinoma (BCC) as one of the most common type of skin cancers reported to have an increasing trend during past years. Molecular approaches can be useful to advance diagnosis and treatment goals in this cancer.Materials and Methods: In this sense, one of the recent popular investigations, protein-protein interaction network analysis (PPI), was applied in this study to better facilitate molecular view of BCC.  Cytoscape v3.6.0 and its plug-ins analyzed and explored the topological and annotation features of the constructed network. Result: Among TP53, EGFR, AKT1, ERBB2, HRAS, and CCND1 as central agents of the network, five of them were also present in the first prominent cluster of the network in which considered for further analysis. It is suggested that there are significant related biological processes, actions, and expression changes for this highlighted cluster that may be related to BCC risk.  Conclusion: Therefore, the studied complex of proteins may worth considering for clinical studies and therapeutic interventions after validating by related tests. What is more, among these genes, EBBR2 has more to offer and consequently with additional values.  [GMJ.2018;7:e1271]

Perbandingan Kinerja Model Convolutional Neural Network pada Klasifikasi Kanker Kulit

Skin cancer is one of the diseases that greatly affects the quality of human life and can be potentially bad if not detected and treated quickly. In an effort to improve the early detection and accuracy of skin cancer diagnosis, this study aims to design a skin cancer classification system using deep learning. The research method involves the use of deep learning-based artificial neural networks, especially convolutional neural networks (CNN), which have been proven effective in image processing. The images in the dataset include various types of skin cancer, including melanoma and basal cell carcinoma. In this study, a skin cancer classification system was built using The-HAM10000 Dataverse, utilizing the CNN algorithm and the performance of the system was modeled using InceptionV3, and EfficientNetB0. The results of these two methods on the dataset show that InceptionV3 has an accuracy of 0.7681, and EfficientNetB0 of 0.9809, the results of this accuracy make the EfficientNetB0 system better for skin cancer detection, so this finding makes that the accuracy at this level will classify as much as 327 data only, therefore the data trained and tested will produce an accuracy and error from its validation which makes EfficientNetB0 an option for classification based on the CNN method.

Minimal Residual Disease-Guided Combination of Ibrutinib and Venetoclax Compared to FCR in Untreated Patients with CLL of Intermediate Risk : Interim Results of MRD Kinetics in the Eradic Trial from the Filo Group

With the emergence of targeted therapies, defining the best strategy for first-line treatment in chronic lymphocytic leukemia (CLL) patients has become challenging. The aim of the ERADIC phase 2 study was to compare the efficacy of a standard FCR regimen to that of an MRD-guided combination of ibrutinib and venetoclax (IV), in fit patients with CLL of intermediate risk defined by either unmutated IGHV status, 11q deletion or complex karyotype in the absence of TP53 alteration. MRD was assessed in bone marrow (BM) or peripheral blood (PB) by flow cytometry. After a lead-in phase of ibrutinib as a single agent from month (M)1 to M3, the total duration of treatment with the IV combination was based on BM M9 MRD. If it was <0.01% (uMRD) at that time, treatment was continued for 6 additional months (M15) then stopped. If M9 BM-MRD was ≥0.01%, IV treatment was continued for 18 additional months (M27). BM-MRD was reassessed at that time-point in both arms. Additionally, PB-MRD evaluation was performed every 6 months.The primary endpoint will be the percentage of patients with BM uMRD at M27. Here, intermediate safety data and MRD kinetics (M9 to M21) are presented. Between September 2019 and February 2021, 120 patients were randomized 1:1 between the two treatment arms. The median age was 59 [34-72] and 61 [34-74] year-old in the FCR and IV arms, respectively. Patient characteristics were well balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV) and Binet stage (A, B and C 15%, 64%, 21% for FCR ; 8.5%, 59% and 32% for IV). An11q deletion was found in 20% and 24% of the cases in the FCR and IV arms, respectively and all patients but one had unmutated IGHV. At the time of data cut-off for this analysis, the median follow-up was 29.7 months [range: 25.3- 32.8]. Sixty-three serious adverse events (SAE) have been reported so far, 32 in the FCR arm and 31 in the IV arm. In the FCR arm, the most frequent SAE were infections (N=12 including 4 COVID-19), febrile neutropenia (N=5) biological tumour lysis syndrome (N=3), and secondary malignancies (N=2, including 1 myelodysplastic syndrome and 1 acute myeloid leukemia). In the IV arm, the most frequently reported SAE were infections (N=8 including 4 COVID-19), cardiovascular events (N=7), biological tumour lysis syndrome (N=5), acute renal failure (N=2) and secondary malignancies (N=2, including 1 colorectal cancer and 1 skin basal cell carcinoma). Four grade 5 adverse events were reported, respectively 2 in the FCR arm (1 septic shock and 1 AML) and 3 in the IV arm (2 sudden deaths and one death COVID-19-related). In the FCR arm (intention to treat [ITT] n=57), 59.6% of the patients had BM-uMRD at M9. The kinetics of PB-uMRD was 68% at M9, 65% at M15 and 52% at M21. In the IV arm (ITT n=54), the rate of BM-uMRD at M9 was much lower at 33%. PB-MRD kinetics showed levels of uMRD of 52%,70% and 67% at M9, M15 and M21 respectively. In terms of response, CR/CRi rates were 56% for the FCR arm and 66% for the IV arm. Three patients progressed in the FCR arm (1 at M9 and 2 at M15) and 2 in the IV arm, at respectively M13 and M39. Among the 13 patients who achieved BM-uMRD at M9 in the IV arm, 10 have indeed stopped according to the protocol and only 1 has progressed at M39. In conclusion, monitoring MRD kinetics in this trial showed a stable level of PB-uMRD in the FCR arm yet a clear increase in the IV arm between M9 and M15. Toxicity remains an important parameter in both treatment arms that will have to be taken into account when determining whether treatment should be continued because of detectable BM-MRD at M9 (IV arm). Upcoming data of the primary enpoint analysis at M27 will be of great interest to try to determine the best strategy.

Anemia and Transfusion Dependency Are Important Prognostic Factors for Overall Survival in Patients with Myelofibrosis: Results of a Real-World Analysis of Medicare Patients

Introduction: Anemia is a hallmark feature of myelofibrosis (MF) and causes many patients (pts) to require red blood cell transfusions. Both anemia and transfusion dependency have been associated with decreased survival in pts with MF. The purpose of this study was to assess the relationship between anemia severity and transfusion dependency on overall survival (OS) among pts with MF in the Medicare population. Methods: This retrospective cohort study used the Medicare fee-for-service database to identify pts with a diagnosis of MF between January 1, 2012, and December 31, 2020. Study inclusion criteria were as follows: (1) ≥1 inpatient or ≥2 outpatient claims for MF (on separate dates <90 days apart; the earliest appearance of MF was set as the MF diagnostic index date [MFDID]); (2) 12 months of continuous enrollment preceding (baseline) and 6 months of continuous enrollment following (follow-up) the MFDID; (3) absence of Janus kinase inhibitor therapy during the 12-month baseline period; (4) absence of polycythemia vera, essential thrombocythemia, or another primary cancer other than basal and squamous cell skin carcinoma during the baseline period; and (5) absence of participation in a clinical trial. Transfusions were assessed over a 180-day landmark period following anemia index date (AID; set to the earliest evidence of anemia, unless it occurred during the 100 days prior to the MFDID, in which the AID was set to the MFDID), and pts were stratified into 3 subcohorts: transfusion independent (TI; no transfusions), transfusion dependent (TD; ≥6 transfusion claims on 6 separate days over any 12-week window), or transfusion requiring (TR; received transfusion claims but did not meet TD criteria). A subset of pts were identified as having anemia based on medical claims from the Medicare fee-for-service database or laboratory test results from the Prognos Biomarker and Laboratory Database ≤100 days before and any time after the MFDID, with severity subcohorts graded based on hemoglobin levels: mild (10 to <12 g/dL), moderate (8 to <10 g/dL), or severe (<8 g/dL) disease. OS from the MFDID was assessed for all pts using Kaplan-Meier analyses, with log-rank tests used to determine statistically significant differences among the transfusion dependency and anemia severity subcohorts. Results: A total of 1749 pts qualified for the transfusion cohorts: 980 were TI, 559 were TR, and 210 were TD. Mean age was 74.8 years, 47.9% were male, and 81.7% were White. Results of Kaplan-Meier analyses showed a median OS of 44.1 months (95% CI, 39.8-48.5 months) for the overall transfusion sample and 62.6 months (95% CI, 57.8-68.2 months) for the TI cohort, 29.0 months (95% CI, 25.9-32.9 months) for the TR cohort, and 22.6 months (95% CI, 20.1-28.1 months) for the TD cohort ( P<.001) (Figure A). A total of 265 pts with corresponding laboratory testing data qualified for the anemia cohorts: 128 were mild, 99 were moderate, and 38 were severe. Mean age was 73.6 years, 47.5% were male, and 79.6% were White. Results of Kaplan-Meier analyses showed a median OS of 64.3 months (95% CI, 56.5-76.9 months) for the overall anemia sample and 89.8 months (95% CI, 72.9 months-not calculable) for the mild cohort, 58.9 months (95% CI, 40.8-69.1 months) for the moderate cohort, and 20.6 months (95% CI, 15.9-49.4 months) for the severe cohort ( P<.001) (Figure B). Conclusions: These results demonstrate that dependency on transfusions, increasing transfusion requirements, and greater anemia severity are each negative prognostic factors for OS among Medicare fee-for-service pts with diagnosed MF. Therapies that reduce transfusion dependency and anemia severity may aid in improving health outcomes and prolong survival in pts with MF. Figure. Kaplan-Meier Curves of Overall Survival in Transfusion (A) and Anemia (B) Subcohorts, Calculated from the Myelofibrosis Diagnostic Index Date

A registration trend in eyelid skin cancers and associated risk factors in Iran, 2005–2016

BackgroundEyelid skin cancers are the most prevalent ophthalmic malignancies. This study aimed to evaluate the association of the Human Development Index (HDI) and lifestyle risk factors with eyelid skin cancers in Iran.MethodsThis ecological study analyzed the data collected from the Iranian National Population-based Cancer Registry (2005–2016). The data on provincial-level eyelid skin cancer risk factors were obtained from national sources. The association between provincial HDI and lifestyle risk factors with the prevalence of eyelid skin cancers was assessed.ResultsThe mean 12-year age-standardized incidence rate (ASIR) of eyelid skin cancers was 16.22 per 100,000 (9,104 cases). The overall ASIR showed an upward trend with an estimated annual average increase of 0.006 per year. There were positive correlations between the prevalence of overall eyelid skin cancers and provincial HDI, smoking, and obesity (r = 0.32, 0.42, and 0.37, respectively). In multivariate analysis, obesity/overweight remained a positive predictor for high prevalence of total eyelid skin cancers (OR = 1.97, 95%CI = 1.08–3.58, P = 0.026), carcinoma (2.10, 1.15–3.83, P = 0.015), and basal cell carcinoma (1.48, 0.99–2.20, P = 0.054).ConclusionsAn increasing trend in ASIR of eyelid skin cancers was observed in more than a decade in Iran which was positively associated with provincial HDI and prevalence of obesity. The findings of the study highlight the importance of promotional programs for preventing obesity/overweight and appropriate allocation of screening facilities based on the HDI level.

On the issue of tolerability and safety of phototherapy in patients with psoriasis

BACKGROUND: Phototherapy using different wavelengths of the ultraviolet (UV) spectrum has been successfully used to treat a variety of dermatoses. Along with the positive effects of this intervention, there are both acute and long-term side effects that should be taken into account by the clinicians.
 AIM: to study the tolerability and safety of phototherapy (PUVA and UVB-311 nm) in patients with moderate to severe psoriasis.
 MATERIALS AND METHODS: There were 920 patients with psoriasis under our supervision from 2005 to 2021, of which 756 (82%) patients suffered from psoriasis vulgaris, 36 (4%) ― guttate psoriasis, 73 (8%) ― exudative psoriasis, 55 (6%) ― inverse psoriasis. 249/920 (27%) were diagnosed with psoriatic arthritis. Patients with moderate psoriasis received 311 nm UVB therapy (n=473), with severe psoriasis ― PUVA therapy (n=447).
 RESULTS: Out of 920 patients with psoriasis during the entire follow-up period, 385 (41.8%) noted one or more early side effects, which were short-lived and disappeared after the end of the PUVA course if the recommendations were followed. Among the early side effects that occurred during the procedures from taking a photosensitizer, the most common were transient nausea, vomiting, dizziness, headache, transient increase in hepatic transaminases. Side effects from the action of ultraviolet rays were reduced to the manifestation of itching, photodermatitis in the form of erythema, photodermatitis in the form of blisters, photoallergic reaction in the form of papular rash, dry skin, photoconjunctivitis, herpes simplex and even photoonycholysis. Patients treated with UVB-311 nm phototherapy complained on xerosis of the skin, itching, photodermatitis in the form of erythema, burning of the skin as early side effects. Long-term side effects in patients treated with PUVA therapy included lentigo (persistent mottled pigmentation), growth of melanocytic neoplasms, PUVA keratosis. In 11 (2.3%) patients with psoriasis who received UVB-311 nm therapy, new nevi appeared. In 42 (9.6%) patients treated with PUVA therapy and in 17 (3.8%) patients treated with UVB-311 nm, signs of photoaging were detected as well. In our study, only 1 (0.2%) patient was diagnosed with facial skin basal cell carcinoma, who received 5 courses of PUVA (119 procedures).
 CONCLUSION: Our study showed that side effects, especially long-term ones, were fewer and significantly less pronounced in patients treated with UVB-311 nm therapy. Comparing the benefits and risks of phototherapy sessions, we can conclude in favor of the effectiveness, good tolerability and safety of PUVA and UVB-311 nm therapy for the treatment of patients with moderate to severe psoriasis. A dose-dependent effect of photoaging was established: the more phototherapy courses were received, the more pronounced the signs of photoaging were, especially after PUVA therapy.

MSH3-related adenomatous polyposis in a patient with the negative family history of colorectal polyps

Recently, biallelic MSH3 germline pathogenic/likely pathogenic variants have been recognized as a rare cause of adenomatous polyposis. We present a 49-year-old woman who was admitted to our high-risk colorectal cancer clinic after incidental detection of a biallelic MSH3 (likely) pathogenic variant when tested for the germline (likely) pathogenic variants in hereditary breast and ovarian cancer related genes. The focus of this case report is to describe the genotype and phenotype of our patient with MSH3-related adenomatous polyposis. More than half of the polyps (13/19) were located in the right colon. In addition, benign and malignant extraintestinal lesions may be common as our patient had simple liver and kidney cysts and two basal cell skin carcinomas.

Cutaneous malignancies in patients with Parkinson's disease at a dermato-oncological university centre in Hungary.

The possible correlation between melanoma and Parkinson's disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary. From 2004 to 2017, a retrospective analysis of the centre's database was performed based on International Statistical Classification of Diseases-10 codes. Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47-0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56-0.98, p=0.0392) but not for melanoma. We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population.

Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche

Cancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.

Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis.

The causality of ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue with basal cell carcinoma (BCC) remains unclear. Our objective was to investigate whether ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue have a relation with the occurrence and development of BCCs. In this work, independent genetic variants strongly associated (P < 5e-08) with ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for BCC was obtained from the European Bioinformatics Institute (EBI). Two-sample univariable and multivariable Mendelian randomization (MR) were performed. Sensitivity analyses were preformed via MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test. We observed positive causal effect both for ease of skin tanning [odds ratio (OR) = 2.102, 95% confidence interval (CI) = 1.915-2.306, P = 2.71e-55] and radiation-related disorders of the skin and subcutaneous (OR = 1.603, 95% CI = 1.483-1.734, P = 3.41e-32) on occurrence of BCCs based on univariable MR analyses. In the multivariable mendelian randomization (MVMR) analysis of BCC risk, we also observed a direct causal effect of ease of skin tanning (ORMVMR = 1.623, 95% CI = 1.445-1.824, PMVMR =3.41e-16) and radiation-related disorders of the skin and subcutaneous (ORMVMR = 1.208, 95% CI = 1.107-1.319, PMVMR = 2.46e-05) on BCCs. The findings suggest that the high risk of BCCs can be attributed to ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue.

256 Non-canonical control of hedgehog signaling in skin basal cell carcinoma

256 Non-canonical control of hedgehog signaling in skin basal cell carcinoma