Gorlin Syndrome-Associated Basal Cell Carcinomas Treated with Vismodegib or Sonidegib: A Retrospective Study.

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors-vismodegib and sonidegib-has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control.

Basosquamous Carcinoma: Comprehensive Clinical and Histopathological Aspects, Novel Imaging Tools, and Therapeutic Approaches.

Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin" in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.

Cemiplimab in Ultra-Octogenarian Patients with Cutaneous Squamous Cell Carcinoma: The Real-Life Experience of a Tertiary Referral Center.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. METHODS: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). RESULTS: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9-14). CONCLUSIONS: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns.

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis.

Introduction: Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD). Methods: We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year. Results: A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity. Conclusions: Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease.

Sonidegib in Locally Advanced Basal Cell Carcinoma: A Monocentric Retrospective Experience and a Review of Published Real-Life Data.

Basal cell carcinoma (BCC) represents the most common skin cancer and locally advanced BCC (laBCC) refers to an aggressive, large, infiltrative BCC that cannot be treated by surgery or radiotherapy. Sonidegib is a Hedghehog inhibitor (HHi) indicated for laBCC. This is a monocentric retrospective real-life study of laBCCs receiving Sonidegib treatment. Although Sonidegib is widely used, since its approval by Food and Drug Administration in 2015, only a limited number of real-life experiences have been reported. Eleven patients, including four patients diagnosed with Basal Cell Naevus syndrome, received treatment with Sonidegib for laBCCs. Seven (63.6%) patients experienced adverse events (AEs) but only three had to discontinue treatment and were therefore excluded from the following results. Four patients (50%) achieved complete clinical remission (CR); in all cases the remission was confirmed by biopsy. Partial response (PR) was found in three patients out of eight (37.5%). One patient out of eight (12.5%) showed a steady disease (SD). None of the patients showed signs of progression during treatment with HHi. Sonidegib showed the same efficacy in treating laBCCs as already seen in trials. All four patients suffering from Basal Cell Naevus syndrome achieved disease control by being treated with Sonidegib. Consequently, we strongly advise the joint management of laBCCs through a multidisciplinary team whenever feasible.

Superficial radiotherapy for non-melanoma skin cancer of the lip: a 44-year Italian experience.

Background: Radiotherapy is a valuable therapeutic option for the treatment of non-melanoma skin cancer (NMSC) in the ageing population, in non-surgical candidates, or when the tumor is extensive or localized in a cosmetically sensitive area such as the lips.Objective: We report our 44-year experience in treating basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the vermilion lip using superficial radiotherapy.Methods: Forty-seven patients with biopsy-proven BCC or SCC of the lip were retrospectively reviewed. All patients had been treated with superficial radiotherapy in our unit, as a primary treatment or with adjuvant and salvage purposes. Lymph-node involvement at presentation was negative in all patients.Results: Local disease control was achieved in 91% of cases. Cure rates of 85% were obtained at 5 and 10 years. Four patients presented local tumor recurrence and only one patient developed lymphatic involvement. Cosmetic outcome was good in the majority of cases, and all patients, except for one, fully preserved the vermilion lip functionality.Conclusions: Our findings confirm that superficial radiotherapy is an effective treatment for early BCC or SCC of the vermilion lip, especially in the ageing population, in high-risk tumors, and even if poor cosmetic outcome is expected from surgical excision.

Hidradenitis suppurativa/acne inversa: a prospective bacteriological study and review of the literature.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle that usually involves specific anatomic areas which are partially occluded, have a higher density of eccrine and apocrine sweat glands and a higher pH. These characteristics could promote the superinfection of certain group of bacteria. We aimed to describe the bacteria that can be isolated from hidradenitis lesions and to establish a correlation between bacteriological results and clinical data. METHODS: We prospectively enrolled forty-six patients presenting purulent or seropurulent discharge. Sixty samples were performed using swabs, which were deeply introduced in the lesions. RESULTS: Fifty-two percent of cultures resulted positive and fifteen bacterial species were isolated. The more prevalent species were Proteus mirabilis and Staphylococcus aureus. Samples from advanced cases were more likely to yield a positive bacterial growth. CONCLUSIONS: In our study the rate of positive cultures increased in more severe stages of the disease, thus bacterial superinfection of established lesions may contribute to maintain chronic inflammation. We could not find statistically significant correlation with the sampled anatomic area or specific group of bacteria. Larger prospective studies should be performed.