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Background: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness. Objectives: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire. Methods: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22–June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated. Results: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21–91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%). Conclusions: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell, and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy. In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers. Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings. [ABSTRACT FROM AUTHOR]

Sonidegib is a HHI (Hedgehog Inhibitor) approved for the treatment of advanced basal cell carcinoma (BCC) with an objective response rate of 60.6% (central review) and 74.2% (investigator review) and a median duration of response of 26.1 months in the pivotal trial BOLT.[1] We herein report the case of a patient with basosquamous carcinomas (BSC) treated with Sonidegib in a neoadjuvant setting. We discussed the case in multidisciplinary tumour board and, considering the extension of the zygomatic lesion and the multiple local recurrences of the other tumours, Sonidegib treatment was started at the regimen of 200 mg daily in May 2020 in a neoadjuvant setting. Moreover, the partial response of the SCC component to HHIs of both tumours of the scalp offered, even in those cases, an easier surgical approach. [Extracted from the article]

Pigmented Bowen's disease is a rare variant of in situ squamous skin cell carcinoma. It mainly affects patients between 60 and 70 years of age. Its clinical features include welldemarcated, pigmented plaque arising in photo-exposed areas of the body. The bestcharacterized feature of the disease by histological examination is the presence of atypical keratinocytes, hyperpigmentation of the epidermis with trans-epidermal elimination of melanin and dermal melanophages. Precise diagnosis is often difficult, both clinically and dermoscopically, as Bowen's disease is often mistaken with keratinocyte tumors such as solar lentigines, seborrheic keratosis, Bowenoid papulosis, pigmented basal cell carcinoma, pigmented actinic keratosis; or even melanocytic lesions such as melanocytic nevus, pigmented epithelioid melanocytoma, and melanoma. Precise diagnosis often requires biopsy and histopathological examination of the tissue. Reflectance confocal microscopy is a noninvasive technique to diagnose pigmented skin lesions. To date, not much data are available regarding its use in the diagnosis of pigmented Bowen's disease. Herein, we report a well-represented case series of pigmented Bowen's disease imaged using dermoscopy and reflectance confocal microscopy. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma is the most common skin tumour, with the majority of the cases occurring on the head and neck district, where cosmetic and functional results are crucial. It can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for most lesions, but aggressive, recurrent, or unresectable tumours can be challenging to manage. Advanced basal cell carcinoma includes high recurrence risk subtypes, in which standard therapies demonstrate lack of efficacy. This led to a need for investigating more deeply the pathogenesis of the disease and to the discovery of the implication of the hedgehog pathway. The development of systemic inhibitors of this pathway provides new treatment options for patients with advanced disease, resulting in survival improvement. Food and Drug Administration, before, and European Medicines Agency later approved 2 Hedgehog pathway inhibitors for the treatment of advanced basal cell carcinomas, vismodegib and sonidegib. Here, we present a review of the current English language literature trying to analyze differences in the 2 drugs as a head-to-head comparison between them has not already been documented in a randomized controlled clinical trial. Although vismodegib and sonidegib showed similar efficacy and safety profiles, in an indirect comparison scenario, sonidegib has shown slightly better outcomes in locally advanced basal cell carcinoma than vismodegib. They present different molecular structures, as they bind different residues on their targets and develop resistance for different mutations. In a future scenario, clinical trials comparing the 2 drugs are needed, as well as expanding data on discontinuation of therapy and/or consequential administration of them, with the aim to improve our clinical practise. [ABSTRACT FROM AUTHOR]

Imiquimod is a 240.3-Da synthetic imidazoquinolinamine (C14H16N4), developed in 1983 and approved in 1997 by the US Food and Drug Administration for the topical treatment of external genital and perianal warts and, more recently, also for actinic keratosis and superficial basal cell carcinomas. We report five cases of patients affected by basal cell carcinomas localized in seborrhoeic areas of the face, successfully treated with topical imiquimod and characterized by the occurrence of eruptive epidermoid cysts at the end-point of therapy. The dermatoscopic evaluation disclosed the presence in all lesions of a common feature characterized by a hyperkeratotic yellow-withish area, resembling 'popcorn', excluding dermoscopic basal cell carcinoma features. Furthermore, histological proof confirmed the diagnosis of epidermoid cysts. As reported in the literature and as observed in our clinical experience, the occurrence of epidermoid cysts, after the topical treatment of basal cell carcinomas with imiquimod, may represent a local immune reaction that is drug-related and is a typical remission pattern in particular anatomical areas. We also emphasized the usefulness of dermoscopy in supporting the clinical diagnosis of epidermoid cysts, excluding the presence of tumoural residue or recurrence. In the future, it will be possible to follow-up the lesions after treatment avoiding the post-control biopsy punch. [ABSTRACT FROM AUTHOR]

BACKGROUND. Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). OBJECTIVE. To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. METHODS. Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. RESULTS. Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). CONCLUSIONS. In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months. [ABSTRACT FROM AUTHOR]

Background: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. Methods: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. Results: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naïve patients with stage II and III basal cell carcinomas, while stage IV disease and not-naïve patients did not show any benefit. Conclusion: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge. [ABSTRACT FROM AUTHOR]

The treatment of advanced basal cell carcinoma has seen a progressive evolution in recent years following the introduction of Hedgehog pathway inhibitors. However, given the burden of mutations in the tumor microenvironment and lack of knowledge for the follow-up of advanced basal cell carcinoma, we are proposing a possible synergistic therapeutic application. Our aim is to underline the use of arsenic trioxide, itraconazole, all-trans-retinoic acid and nicotinamide as possible adjuvant therapies either in advanced not responding basal cell carcinoma or during follow-up based on Hedgehog pathway. We have analyzed the rational use of these drugs as a pivotal point to block neoplasm progression, modulate epigenetic modification and prevent recurrences. [ABSTRACT FROM AUTHOR]

Basal cell carcinomas (BCCs) are the most common nonmelanoma skin cancers. Dermoscopy is an indispensable tool to differentiate superficial BCC from other subtypes and between pigmented and not pigmented ones. Although surgery is considered the gold‐standard therapy, new current pharmacological options are available and focus on tumor eradication, increasing cosmetic results and functionality. 5‐fluorouracil (5‐FU) is a cytostatic drug associated with antimetabolite effects and already approved as monotherapy for superficial BCCs treatment. A recent formulation combining of 5‐FU 0.5% with salicylic acid 10% has been indicated for the management of slightly palpable and/or moderately thick hyperkeratotic actinic keratosis of the face, forehead, and balding scalp in immunocompetent adult patients. This formulation has never been used as treatment for superficial BCC. In this article, we reported superficial BCC clinical and dermoscopic outcomes in two patients treated with this new topical agent, to assess its role in treating these lesions and to point out dermoscopy's usefulness in supporting clinical diagnosis and excluding tumor persistence or recurrence. [ABSTRACT FROM AUTHOR]

The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group. [Display omitted] • Provide some important updates: • Epidemiological characteristics of NMSC affected patients for each type of lesion. • Association between each type of NMSC and the history of exposure-related factors. • Correlation of different skin tumors with each other, including melanoma. [ABSTRACT FROM AUTHOR]

A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (8CC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated 8CC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-β and bax expression, with RAR-α, and -γ expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-β and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces 8CC regression possibly by synergistic RAR-β-dependent anti-proliferative and proapoptotic pathways. [ABSTRACT FROM AUTHOR]