Cutaneous Cancer Research Articles

Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis.

Background: Cutaneous squamous cell carcinoma (cSCC) is a common cutaneous cancer with increasing incidence. Itraconazole has been identified as a potential anticancer drug candidate. However, the role of itraconazole in cSCC was still unclear. Our objective is exploring the therapeutic potential of itraconazole in cSCC and investigate its molecular mechanism. Methods: The anti-proliferation effect of itraconazole was tested with CCK-8 assay and clone formation assay. Cell cycle distribution and apoptosis rate were detected using flow cytometry and TUNEL assay, respectively. Transcriptomic and proteomic analyses were used to explore the underlying anti-cancer mechanism. Luciferase reporter assay was used for promoter activity. Reactive oxygen species (ROS), lipid peroxidation and iron accumulation were examined. The in vivo efficacy of itraconazole was assessed in a xenograft model. Results: Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of cSCC cells. An integrated analysis of transcriptomic and proteomic analyses identified that 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. HMGCS1 silencing reversed the antiproliferative activity of itraconazole in A431 cells. Dual-luciferase assay showed that itraconazole could promote HMGCS1 transcription. HMGCS1 silencing abated the expression of ACSL4 in A431 cells. The level of ROS, lipid peroxidation, as well as iron accumulation were increased by itraconazole. Moreover, treatment with itraconazole impeded tumor growth in A431-bearing mice. Conclusion: We proved itraconazole inhibits the growth of cSCC by regulating HMGCS1/ACSL4 axis.

Elevated Levels of Soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and Systemic Inflammatory Stress as Potential Contributors to Immune Suppression and Generalized Tumorigenesis in a Cohort of South African Xeroderma Pigmentosum Patients.

Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-γ (IFN- γ) and tumor-necrosis factor-α (TNF-α), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (P<0.01) and TNF-α (P<0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (P=0.032-P=0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both P<0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (P=0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.

Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry.

BackgroundLimited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States.MethodsThis prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor–naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings.ResultsDetermination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment.ConclusionsThis prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

A New Approach for a Safe and Reproducible Seeds Positioning for Diffusing Alpha-Emitters Radiation Therapy of Squamous Cell Skin Cancer: A Feasibility Study.

The purpose of this study is to discuss how to use an external radio-opaque template in the Diffusing Alpha-emitters Radiation Therapy (DaRT) technique's pre-planning and treatment stages. This device would help to determine the proper number of sources for tumour coverage, accounting for subcutaneous invasion and augmenting DaRT safety. The procedure will be carried out in a first phase on a phantom and then applied to a clinical case. A typical DaRT procedure workflow comprises steps like tumour measurements and delineation, source number assessment, and therapy administration. As a first step, an adhesive fiberglass mesh (spaced by 2 mm) tape was applied on the skin of the patient and employed as frame of reference. A physician contoured the lesion and marked the entrance points for the needles with a radio opaque ink marker. According to the radio opaque marks and metabolic uptake the clinical target volume was defined, and with a commercial brachytherapy treatment planning system (TPS) it was possible to simulate and adjust the spatial seeds distribution. After the implant procedure a CT was again performed to check the agreement between simulations and seeds positions. With the procedure described above it was possible to simulate a DaRT procedure on a phantom in order to train physicians and subsequently apply the novel approach on patients, outlining the major issues involved in the technique. The present work innovates and supports DaRT technique for the treatment of cutaneous cancers, improving its efficacy and safety.

Perineural Spread of Melanoma: Lessons Learned the Hard Way

Asra Nayab, Muhammad Hammad Malik, Anusha Parisapogu, Arunima Sharma, Juna Musa, David R. DeLone, Judith Jebastin Thangaiah, Aditya Raghunathan and Darya Shlapak Extension of tumor cells along the perineural environment is referred to as perineural spread. Amongst the head and neck malignancies, nonmelanoma cutaneous or non-cutaneous cancers such as squamous cell carcinoma, adenoid cystic carcinoma and lymphoma are the more common malignancies known to spread perineurally.

In-transit metastasis of cutaneous squamous cell carcinoma: report of two cases

Transit metastases include metastatic foci of the skin and subcutaneous tissue located between the tumor and the nearest regional lymph node. Although transit metastases have been described for malignant melanoma, some cases of transit metastases have also been reported among primary cutaneous non-melanoma cancers. Treatment of patients with in-transit squamous cell carcinoma (SCC) is a multimodal approach for advanced staging imaging and therapy, including Mohs micrographic surgery, adjuvant radiation, and possibly sentinel lymph node biopsy and immunotherapy or chemotherapy. Here we report two cases of in-transit metastasis with primary cutaneous SCC.

Multiple datasets to explore the tumor microenvironment of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent types of cutaneous cancer. The composition and heterogeneity of the tumor microenvironment significantly impact patient prognosis and the ability to practice precision therapy. However, no research has been conducted to examine the design of the tumor microenvironment and its interactions with cSCC. We retrieved the datasets GSE42677 and GSE45164 from the GEO public database, integrated them, and analyzed them using the SVA method. We then screened the core genes using the WGCNA network and LASSO regression and checked the model's stability using the ROC curve. Finally, we performed enrichment and correlation analyses on the core genes. We identified four genes as core cSCC genes: DTYMK, CDCA8, PTTG1 and MAD2L1, and discovered that RORA, RORB and RORC were the primary regulators in the gene set. The GO semantic similarity analysis results indicated that CDCA8 and PTTG1 were the two most essential genes among the four core genes. The results of correlation analysis demonstrated that PTTG1 and HLA-DMA, CDCA8 and HLA-DQB2 were significantly correlated. Examining the expression levels of four primary genes in cSCC aids in our understanding of the disease's pathophysiology. Additionally, the core genes were found to be highly related with immune regulatory genes, suggesting novel avenues for cSCC prevention and treatment.

Treatment and survival outcomes in metastatic Merkel cell carcinoma: Analysis of 2010 patients from the SEER database

Introduction: Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer that frequently compromises the lymph nodes (LN) and distal organs. We sought to describe clinical and demographic characteristics of affected patients, analyze risk factors for LN compromise, metastasis, and death, and evaluate their impact on survival. Materials and Methods: Patients with MCC were retrieved from the SEER database. Demographic, clinical and treatment data were analyzed. Logistic and Cox proportional hazard regression were used to analyze risk factors. Survival analysis was done with the Kaplan-Meier method. Results: A total of 2010 patients were included, among which 288 (14.33%) had distant metastases at diagnosis. LN involvement occurred in 45.8% and 20.1% of patients with and without distant metastasis, respectively. Males were more likely to present LN compromise (OR = 1.33, p<0.001). Tumors >10 mm showed a significantly higher risk for LN involvement and distant metastasis, with those >20 mm showing the highest risk (OR = 2.76 p<0.001 and OR = 8.88 p<0.001 respectively). Location of the tumor in the trunk was a protective factor for overall death (OR = 0.27), while LN compromise was a risk factor (OR = 3.12). Only history of previous malignancy significantly affected disease-specific death (OR = 0.32, p = 0.01). One-year survival was 79.7% and 38.2% for patients with regional LN disease and distant metastasis, respectively. Conclusion: MCC is an aggressive cancer with high rates of LN involvement and distant metastases. Male gender and tumor size were risk factors for regional LN and metastatic disease. Tumor location in the trunk decrease the risk of overall death, while LN involvement increased it.

Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study.

Background Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4-25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7-31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4-10.3. Limitations The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Berberine as a Potential Anticancer Agent: A Comprehensive Review

Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial–mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.

The deleterious effects induced by an acute exposure of human skin to common air pollutants are prevented by extracts of Deschampsia antarctica

The homeostatic and regenerative potential of the skin is critically impaired by an increasing accumulation of air pollutants in human ecosystems. These toxic compounds are frequently implicated in pathological processes such as premature cutaneous ageing, altered pigmentation and cancer. In this scenario, innovative strategies are required to tackle the effects of severe air pollution on skin function. Here we have used a Human Skin Organotypic Culture (HSOC) model to characterize the deleterious effects of an acute topic exposure of human skin to moderately high concentrations of common ambient pollutants, including As, Cd, Cr, dioxins and tobacco smoke. All these toxic compunds inflict severe damage in the tissue, activating the AHR-mediated response to xenobiotics. We have further evaluated the potential of an aqueous leaf extract of the polyextremophile plant Deschampsia antarctica (Edafence) to protect human skin against the acute exposure to toxic pollutants. Our results indicate that pre-treatment of HSOC samples with this aqueous extract conuterbalances the deleterious effects of the exposure to toxic comunds and triggers the activation of key genes invoved in the redox system and in the pro-inflammatory/wound healing response in the skin, suggesting that this natural compound might be effectively used in vivo to protect human skin routinely in different daily conditions.

Gene Expression Studies in Formalin-Fixed Paraffin-Embedded Samples of Cutaneous Cancer: The Need for Reference Genes.

Formalin-fixed paraffin-embedded (FFPE) tumour samples may provide crucial data regarding biomarkers for neoplasm progression. Analysis of gene expression is frequently used for this purpose. Therefore, mRNA expression needs to be normalized through comparison to reference genes. In this study, we establish which of the usually reported reference genes is the most reliable one in cutaneous malignant melanoma (MM) and cutaneous squamous cell carcinoma (CSCC). ACTB, TFRC, HPRT1 and TBP expression was quantified in 123 FFPE samples (74 MM and 49 CSCC biopsies) using qPCR. Expression stability was analysed by NormFinder and Bestkeeper softwares, and the direct comparison method between means and SD. The in-silico analysis with BestKeeper indicated that HPRT1 was more stable than ACTB and TFRC in MM (1.85 vs. 2.15) and CSCC tissues (2.09 vs. 2.33). The best option to NormFinder was ACTB gene (0.56) in MM and TFRC (0.26) in CSCC. The direct comparison method showed lower SD means of ACTB expression in MM (1.17) and TFRC expression in CSCC samples (1.00). When analysing the combination of two reference genes for improving stability, NormFinder indicated HPRT1 and ACTB to be the best for MM samples, and HPRT1 and TFRC genes for CSCC. In conclusion, HPRT1 and ACTB genes in combination are the most appropriate choice for normalization in gene expression studies in MM FFPE tissue, while the combination of HPRT1 and TFRC genes are the best option in analysing CSCC FFPE samples. These may be used consistently in forthcoming studies on gene expression in both tumours.

Vitamin D and Skin Cancer: An Epidemiological, Patient-Centered Update and Review.

Background: The current vitamin D deficiency epidemic is accompanied by an increase in endemic skin cancer. There are still multiple controversies. This review aims to give practical recommendations regarding vitamin D among people at risk or with a personal history of skin cancer. Methods: Narrative review including human research articles published between 2011 and 2021, elaborated bearing in mind an epidemiological, patient-centered approach. Results: Ultraviolet (UV) exposure (neither artificial nor natural) is not the ideal source to synthesize vitamin D. There is conflicting epidemiological evidence regarding vitamin D, non-melanoma skin cancer (NMSC), and cutaneous melanoma (CMM), confounded by the effect of sun exposure and other factors. Conclusions: Current evidence is controversial, and there are no widely applicable strategies. We propose three practical recommendations. Firstly, sun protection recommendations should be kept among people at risk or with a personal history of skin cancer. Secondly, vitamin D should preferably be sourced through diet. In patients with melanoma or at risk of cutaneous cancer, serum vitamin D checks are warranted to detect and avoid its insufficiency.

Combined CO2 and dye laser technique in the treatment of outcomes due to flap necrosis after surgery for basal cell carcinoma on the nose

AbstractBackground and ObjectiveBasal cell carcinoma (BCC) is the most frequent cutaneous cancer worldwide, and the nasal area is the most commonly affected region. Skin flaps are usually performed to achieve radical results, but various adverse events often occur. The necrosis of the skin flap is one of the most frequently observed, resulting in scars and anti‐aesthetic outcomes. Ablative and non‐ablative lasers have been proposed to improve scars resulting from surgical failure and skin flap necrosis.Study Design/Materials and MethodsThis study aims to evaluate a new laser protocol combining ablative CO2‐laser with flashlamp pulsed dye laser for the treatment of nasal scars resulting from the necrosis of flap that occurred after surgery. Twelve patients were enrolled in the study, and a total of five laser sessions were planned, spaced from 14 days to 1 month apart.ResultsSeven out of 12 patients underwent all the five laser sessions planned, while 5/12 patients achieved optimal cosmetic results within the fourth session. Eighty percent of the patients reported good/optimal cosmetic results, and no significant side effects were observed during the study.ConclusionCombining fractionated CO2 laser with flashlamp pulsed dye laser represents a new effective modality for treating skin flap necrosis after BBC removal, representing a valid alternative to other surgical procedures.

A Lipidomic Approach to Identify Potential Biomarkers in Exosomes From Melanoma Cells With Different Metastatic Potential.

Melanoma, one of the most lethal cutaneous cancers, is characterized by its ability to metastasize to other distant sites, such as the bone. Melanoma cells revealed a variable in vitro propensity to be attracted toward bone fragments, and melanoma-derived exosomes play a role in regulating the osteotropism of these cells. We have here investigated the lipid profiles of melanoma cell lines (LCP and SK-Mel28) characterized by different metastatic propensities to colonize the bone. We have purified exosomes from cell supernatants by ultracentrifugation, and their lipid composition has been compared to identify potential lipid biomarkers for different migration and invasiveness of melanoma cells. Matrix-assisted laser desorption ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS) lipid analysis has been performed on very small amounts of intact parental cells and exosomes by skipping lipid extraction and separation steps. Statistical analysis has been applied to MALDI mass spectra in order to discover significant differences in lipid profiles. Our results clearly show more saturated and shorter fatty acid tails in poorly metastatic (LCP) cells compared with highly metastatic (SK-Mel28) cells, particularly for some species of phosphatidylinositol. Sphingomyelin, lysophosphatidylcholine, and phosphatidic acid were enriched in exosome membranes compared to parental cells. In addition, we have clearly detected a peculiar phospholipid bis(monoacylglycero)phosphate as a specific lipid marker of exosomes. MALDI-TOF/MS lipid profiles of exosomes derived from the poorly and highly metastatic cells were not significantly different.

Non-invasive diagnostic techniques in pigmentary skin disorders and skin cancer.

Diagnosis of pigmentary skin disorders, pre-cancerous and cancerous skin diseases is traditionally relied on visual assessment. The most widely applied invasive diagnostic technique is the skin biopsy. There have been significant technological advances in non-invasive diagnostic methods for skin disorders. The objective of this article is to discuss different non-invasive diagnostic modalities, used in the diagnosis of pigmentary skin disorders and cutaneous cancers. Comprehensive literature search was performed to screen articles related to non-invasive diagnostic techniques in pigmentary skin disorders and cutaneous cancers. Articles published in journals indexed in PubMed were searched along with those in Google Scholar. Clinical trials, review articles, case series, case reports and other relevant articles were considered for review. References of relevant articles were also considered for review. Dermoscopy and ultrasonography were the only non-invasive diagnostic and imaging techniques available to dermatologists for many years. The advent of computed tomography (CT) and magnetic resonance imaging (MRI) augmented the visualization of deeper structures. Confocal laser microscopy (CLM) and reflectance spectrophotometers have showed promising results in the non-invasive detection of pigmented lesions. Optical coherence tomography (OCT), electrical impedance spectroscopy (EIS), multispectral imaging, high frequency ultrasonography (HFUS) and adhesive patch biopsy aid in the accurate diagnosis of benign, as well as neoplastic skin diseases. There have been significant advancements in non-invasive methods for diagnosis of dermatological diseases. These techniques can be repeatedly used in a comfort manner for the patient, and may offer an objective way to follow the course of a disease.

Uterine leiomyomatosis in adolescents and young adults (AYAs) may represent a narrow phenotypic variant of FH tumour predisposition syndrome

FH Tumour Predisposition Syndrome, also known as Hereditary Leiomyomatosis and renal cell cancer (HLRCC), or Reed Syndrome, is an autosomal dominant condition clinically characterized by multiple cutaneous leiomyomas, multiple early-onset uterine leiomyomas and early-onset renal cell cancer. Here we report a young female with FH Tumour Predisposition Syndrome with no clinical features except early-onset uterine leiomyomas. Whilst there is a significant history of uterine leiomyomas in her family, there is no history of cutaneous leiomyomas or renal cell cancer (RCC). Uterine leiomyomatosis in young adults may represent a narrow phenotypic variant of FH Tumour Predisposition Syndrome. It is important that young women who present with multiple leiomyomata or leiomyomata with atypical features are referred for molecular genetic testing.

Diagnostic yield of staging brain magnetic resonance imaging is low in Merkel cell carcinoma: A single-institution cohort study

To the Editor: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine cancer that seldom presents with brain metastasis. Here we present the diagnostic yield of brain magnetic resonance imaging (MRI) at presentation (<90 days from pathologic diagnosis) from a cohort of 77 cases diagnosed between 2016 and 2020 available from the Mass General Brigham medical record. Our data demonstrate that staging brain MRI rarely yields positive findings, suggesting that routine brain imaging, particularly for the majority of patients who present without neurologic symptoms, may not be indicated.

Response of advanced cutaneous squamous cell carcinoma to immunotherapy: case report

The most common cancer in the United States is non-melanoma skin cancer. Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer after basal cell carcinoma. It develops in the middle and outer layers of the skin. Its precursor is actinic keratosis, which can progress to squamous cell carcinoma in situ, invasive cSCC, and finally metastatic cSCC. About 20% of non-melanoma skin cancers are squamous cell and the remaining 80% are basal cell. Unlike basal cell, squamous cell carcinoma has the propensity to metastasize. This commonly occurs with squamous cell carcinoma (SCC) thicker than 2 millimeters. The risk of metastasis and local recurrence increases with 6 mm thickness and desmoplasia. The risk factors are excessive sun or ultraviolet light (tanning beds) exposure, immunosuppression (either having a weakened immune system or taking immunosuppressive therapy) and fair skin. Therefore, it most commonly affects skin in the head and neck area such as scalp, ears, lips, face, neck or the back of the hands. The treatment for local cutaneous squamous cell cancer is mainly surgery; excisional surgery, Moh's surgery, cryosurgery, curettage and electrodessication, laser surgery or radiation therapy, photodynamic therapy or topical agents such as fluorouracil or imiquimod. However, cSCC that is locally advanced, such as involvement of regional lymph nodes, or has metastasized to distant organs or tissue, is not amenable to surgery or radiation alone. Immunotherapy with cemiplimab, a programmed cell death 1 (PD-1) inhibitor, is a US Food and Drug Administration (FDA) approved therapeutic option for locally advanced and metastatic cSCC for patients who are not candidates for or whose disease is not susceptible to curative surgery or radiation therapy. Cemiplimab is a humanized recombinant immunoglobulin monoclonal antibody that binds to and blocks PD-1 receptor found on T cells inhibiting T-cell proliferation and cytokine production. We present a case of locally advanced cSCC with regional lymph nodes metastases, which achieved clinical remission, utilizing a unique approach of therapy combining a checkpoint inhibitor, Cemiplimab and radiotherapy.

Carcinoma en cuirasse associated to zosteriform metastasis from breast adenocarcinoma

We report an original case of carcinoma en cuirasse associated with zosteriform metastasis. A 40-year-old woman presented to our department with painful erythematous lesions. She had a history of invasive ductal carcinoma of the left breast. Numerous erythematous, papules and whitish vesicles were present over the right side of the chest in a dermatomal distribution with indurated coalescent plaques. Biopsy revealed metastatic carcinoma of breast origin. Breast mammography showed suspicious right nodule. Controlateral breast carcinoma with CM was diagnosed. CM show a wide range of clinical manifestations. Carcinoma en cuirasse, is a very rare form of metastatic cutaneous breast cancer. It is characterized by diffuse sclerodermatous induration of the skin. Zosteriform metastasis is also rarely seen. It may be distributed along dermatomeres in a variety of clinical patterns, including nodular, papulovesicular, or vesiculobullous. In our case, the zosteriform metastasis occurred in the contralateral site. It announced the developing of contralateral breast cancer.