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.

Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients.

BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.

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.

The role of radiotherapy in the management of cutaneous squamous cell carcinoma: a retrospective study on 92 cases.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in the world after basal cell carcinoma. Treatment of choice for cSCC is surgery, but radiotherapy (RT) is a valid alternative and has been recommended in selected cases. The aim was to evaluate the cure rate of RT for cSCC and to compare the results in the two settings of RT as exclusive or second line treatment. METHODS: The outcome of 92 cSCC treated with RT in the period from 2002 to 2019 in our department was retrospectively reviewed. RESULTS: In 56 cases RT was first-line treatment while in 36 it was administered as second-line treatment after incomplete excision or failure of previous treatments. The five-year cure-rate was 74% (71.34% in patients treated with primary RT and 77.37% in patients treated with RT as second-line treatment), while the ten-year cure-rate was 67% (57.07% and 77.37% respectively in patients treated with primary RT or with second line RT). Log rank test showed statistical significance between the cure-rate of the two groups with better therapeutic results after second-line RT (P<0.05). CONCLUSIONS: Our data confirm RT as an effective therapy for cSCC when surgery excision is contraindicated or in case of tumors localized in certain regions where the cosmetic-functional outcome is better than surgery. Better therapeutic results are achieved with second-line RT.

Acquired unilateral facial melanocytosis: nevus of Sun.

Acquired dermal melanocytoses include pigmented lesions with a clear late onset, histologically characterized by the presence of melanocytes in the dermis. In this report, we describe a rare case of acquired unilateral facial melanocytosis, also called nevus of Sun, in a Caucasian woman.

Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature.

Gefitinib is a selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) used for the treatment of malignant neoplasms. The most frequent skin complication during gefitinib therapy is an acneiform papulopustular eruption, usually distributed in the seborrheic areas but occasionally widespread. We report a patient with erosive pustular dermatosis of the scalp, a neutrophil-mediated skin disease presenting with sterile pustules evolving into erosions and crusts on the scalp, during treatment with the EGFR inhibitor gefitinib for lung cancer. A literature review of the drug-induced cases of this rare entity is provided.

Mucosal Kaposi's sarcoma in HIV-negative patients: a large case series from a single, tertiary referral center in Italy.

BACKGROUND: Mucosal involvement in HIV-negative Kaposi's sarcoma (KS) is uncommon but has potentially serious repercussions on patient care. Evidence regarding its epidemiology and optimal management is limited. Invasive endoscopic staging at diagnosis and periodically during follow-up is currently recommended by major guidelines. MATERIALS AND METHODS: We reviewed the clinical records of 1,308 HIV-negative KS patients followed at our dedicated KS outpatient service. Demographics, clinical characteristics, and treatment outcomes for cases with biopsy proven mucosal lesions were collected. RESULTS: Mucosal involvement was documented in 53 patients (4.1% of our cohort), being present at diagnosis in 28 (52.8%) and occurring at a later time in the remaining 25 (47.2%) patients, with a mean latency of 8 years (±7.7). Oral cavity (43.4%) and glans penis (39.6%) were the most frequently involved anatomical sites. Of those with available treatment response data, complete response (CR) of mucosal KS was appreciated in 41 cases (93.2%), while partial response (PR) and stable disease (SD) were documented in one (2.3%) and two cases (4.5%), respectively. Same-site recurrences were noticed in seven patients (17.1%). CONCLUSION: Mucosal involvement in HIV-negative KS is rare, and its recurrence, if properly treated, appears to be infrequent. Thus, routine invasive monitoring in this setting may be unnecessary. We propose a tailored approach based on the clinical manifestations of each patient, limiting the indication of invasive procedures to the first evaluation and in case of significant clinical worsening or to monitor known mucosal localizations.

Oral nicotinamide: The role in skin cancer chemoprevention.

The incidence of skin cancer has gradually increased in the last years and exposition to ultraviolet radiation remains the main risk factor. We performed a comprehensive review on the role of nicotinamide (NAM) in the chemoprevention of skin cancers. NAM, a water-soluble form of vitamin B3, interferes with skin carcinogenesis as it regulates immunosuppressor genes such as p53 and sirtuins and restores intracellular level of NAD+, a co-enzyme essential for energy production. Efficacy and safety of NAM was evaluated in a Phase III double-blinded control-placebo study (ONTRAC), thus demonstrating that the incidence of actinic keratoses and non-melanoma skin cancers was lower in the nicotinamide group than in placebo group. Further studies showed the efficacy of NAM also in transplanted patients and among inhabitants living in arsenic contamination areas. Despite the quick response to NAM supplementation, its intake need to be carried on chronically as the efficacy seems to vanish rapidly.

Hyperkeratosis lenticularis perstans (Flegel's disease): our experience and review of the literature.

Hyperkeratosis lenticularis perstans (HLP), or Flegel's disease (FD), is a rare disorder of keratinization first described in 1958 by Flegel. HLP is characterized by asymptomatic small papules distributed symmetrically on the dorsal feet and lower part of the legs. It typically presents in the fourth or fifth decade of life. FD has been reported more commonly in women, and little is known about the pathogenesis of this rare dermatosis. Histological examination is mandatory to confirm the diagnosis, and the characteristic features are: focal compact hyperkeratosis, thinned stratum malpighii, epidermal atrophy, and a dense, band-like lymphocytic infiltrate in the papillary dermis. The treatment of FD is challenging, and a fully effective standard therapy does not exist. We report four cases of HLP that have been diagnosed at the Dermatology Unit of IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy, and a literature review is enclosed.

Cervicofacial actinomycosis: a report of 14 patients observed at the Dermatology Unit of the University of Milan, Italy.

BACKGROUND: Actinomycoses are rare chronic infections often caused by Actinomyces spp. Cervicofacial actinomycosis (CFA) is caused by primary lesions in the oral cavity and subsequent fistulae, and suppurative and granulomatous lesions on the skin of the face. METHODS: We present the results of a retrospective study on 14 patients with CFA, observed in the period 1984-2019 at the Dermatology Unit of the University of Milan. Physical general and dermatologic examinations, instrumental tests, and histopathologic and bacteriologic examinations were carried out in all patients. In three patients, polymerase chain reaction was also carried out. RESULTS: Six patients showed poor oral hygiene; eight patients had been subjected to previous surgical operations in the oral cavity. Histopathologic examination was superimposable in all patients. In four patients, bacteriologic examinations were positive for A. israelii. In three patients, polymerase chain reaction was positive for A. israelii. X-rays of the bones of the face showed osteolytic lesions in four patients. All patients were successfully treated with benzathine benzylpenicillin followed by amoxicillin or with amoxicillin in monotherapy. In all patients, surgical drainage and debridement of the oral cavity were carried out. CONCLUSION: CFA is a rare infection caused by primary lesions in the oral cavity and subsequent fistulae, and nodular and ulcerative lesions on the skin of the face. Clinical diagnosis must be confirmed by histopathologic, bacteriologic, and instrumental examinations. Therapy with penicillins is usually very long and must be accompanied by surgical drainage and debridement of the oral cavity.