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.

A Multidisciplinary Approach to Patients with Psoriasis and a History of Malignancies or On-Treatment for Solid Tumors: A Narrative Literature Review.

Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions.

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.

The role of imaging technologies in the diagnosis of hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic, inflammatory, recurrent, and debilitating disease of the hair follicle. It presents with painful, deep-seated, inflamed lesions, such as nodules, abscesses, sinus tracts, and fistulas, generally located in the main folds. Clinical severity assessment alone can be reductive; noninvasive skin imaging technologies, such as ultrasound, magnetic resonance imaging, medical infrared thermography, computed tomography, and positron emission tomography, provide subclinical anatomical and functional details. These instrumental techniques confirm the clinical suspect, thus allowing an earlier diagnosis and improving patients' clinical evaluation, staging, and management. Finally, they might be helpful for preoperative mapping. In this contribution, we provide an overview of the current knowledge about noninvasive skin imaging techniques with a particular focus on ultrasonography, which is widely used thanks to its precision, versatility, and availability.

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.

Dermoscopic predictors of melanoma in small diameter melanocytic lesions (mini-melanoma): a retrospective multicentric study of 269 cases.

BACKGROUND: Incidence of cutaneous melanoma is steadily growing, and its early recognition is of paramount importance. Small, pigmented lesions often represent a challenge for the clinician, as predictors of melanoma have not yet been uniquely identified in this setting. OBJECTIVES: To identify dermoscopic features that aid in distinguishing small diameter melanomas (≤5 mm) from equivocal melanocytic nevi measuring ≤5 mm. METHODS: A retrospective multicenter study was conducted to collect demographics, clinical and dermoscopic pictures of (i) histology-proven flat melanomas, measuring ≤5 mm, (ii) histology-proven but clinically/dermoscopically equivocal melanocytic nevi measuring ≤5 mm, and (iii) histology-proven flat melanomas, measuring >5 mm. An independent dermoscopic evaluation was performed. Differences in predefined dermoscopic features were assessed across the three groups. RESULTS: A total of 103 melanomas measuring ≤5 mm were collected; 166 control lesions, comprising 85 large (>5 mm) melanomas and 81 dubious, clinically equivocal melanocytic nevi measuring ≤5 mm were included. Of the 103 mini-melanomas, only 44 were melanoma in situ. Five dermoscopic predictors of melanoma were identified for the assessment of flat, non-facial melanocytic lesions measuring ≤5 mm, namely: atypical pigment network, blue-white veil, pseudopods, peripheral radial streaks, and presence of more than one color. The latter were combined into a predictive model capable of identifying melanoma with 65% sensitivity and 86.4% specificity, at a cut-off score of 3. Among melanomas measuring ≤5 mm, presence of a blue-white veil (P = 0.0027) or negative pigment network (P = 0.0063) was associated with invasiveness. CONCLUSION: A set of five dermoscopic predictors of melanoma, atypical pigment network, blue-white veil, pseudopods, peripheral radial streaks, and presence of more than one color is proposed for the assessment of flat, non-facial melanocytic lesions measuring ≤5 mm.

Mohs micrographic surgery: the experience of the dermatology unit of the university of Milan confirms the superiority over traditional surgery in high-risk non-melanoma skin cancers.

The constant increase in the incidence of non-melanoma skin cancers (NMSC) makes their treatment a topic of paramount interest. Because most NMSC tend to develop in visible areas such as the headneck area, it is a priority to choose the less destructive therapy and more appropriate reconstructive technique. Mohs Micrographic Surgery (MMS) represents the treatment of choice for skin tumors in critical sites, recurrent tumors and tumors with aggressive histologic features. We collected patients affected by NMSC who underwent MMS at the Dermatology Unit of IRCCS Fondazione Ca' Granda, Milan, in the period March 2017-December 2021. One hundred and fifty-nine patients were enrolled in this retrospective observational study. The excision margins were chosen based on a dermoscopic evaluation. The main histological diagnoses were basal cell carcinoma (145, 91.2%) and squamous cell carcinoma (10, 6.3%), in areas with high functional or anatomical value. 121 out of 159 surgeries did not require further enlargement after the removal of the clinically and dermoscopically visible lesion, but in 38 cases (23.9% of cases) the pathologist required at least one subsequent enlargement, due to the persistence of neoplasm at the bottom or at the margins of the lesion. Only one recurrence has been reported so far. MMS is a pathology-controlled surgery with high intrinsic value because of the low risk of recurrences and should be routinely adopted for high-risk NMSC.

Dermoscopy Use Leads to Earlier Cutaneous Melanoma Diagnosis in Terms of Invasiveness and Size? A Single-Center, Retrospective Experience.

Background: The incidence of cutaneous melanoma has risen in recent years. The aim of this study was to compare cutaneous melanomas diagnosed at the Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, from 2006 to 2020 and between two specific biennia, i.e., 2006−2007 and 2019−2020. Methods: Retrospective chart review, with dermoscopic image collection, of cutaneous melanomas diagnosed at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, from 1 January 2006 to 31 December 2020 Results: A statistically significant increase was shown in the proportions of in situ melanoma and melanoma measuring less than 6 mm, i.e., small-diameter melanoma (SDM), across the studied period (p < 0.001). Moreover, in the biennium 2006−2007, among 220 melanoma diagnoses, 6 were in situ (2.7%), as compared with 68 melanomas in situ out of a total of 236 (28.8%) melanomas diagnosed in the biennium 2019−2020. A statistically significant difference in the proportion of in situ melanoma between the two biennia was demonstrated (p < 0.001). Furthermore, during the first biennium, 27/220 (12.3%) SDM were identified, as compared with 61/236 (25.9%) in the last. A statistically significant difference was shown in the proportion of SDM between the two (p < 0.001). Conclusions: The percentage of in situ melanomas and those that can be detected at a diameter <6 mm has increased. The latter has been shown to be around one-third of excised lesions, thus undermining the practicality of the ABCD mnemonic. Dermoscopic criteria for SDM are needed to help further refine melanoma diagnosis.

Basal Cell Carcinoma and Hedgehog Pathway Inhibitors: Focus on Immune Response.

Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting more often elderly patients, but sometimes even younger ones, particularly if immunocompromised or genetically predisposed. Specifically, the Gorlin-Goltz syndrome, an autosomal dominant genodermatosis, also known as nevoid basal cell carcinoma syndrome, characterizes for multiple early onset BCCs. It is caused by a germline mutation in PTCH1, a tumor suppressor gene whose product is the key component of Hedgehog (Hh) signaling pathway, which also appears somatically mutated in more than 85% of sporadic BCCs. Hh pathway inhibitors vismodegib and sonidegib are currently indicated for BCC, in adults with advanced or recurred tumor following surgery or radiation therapy. The principal mechanism of action of these drugs is the inhibition of Smoothened (SMO), a transmembrane protein involved in Hh signal transduction, that plays a role in both cellular differentiation and cancer development. Some studies have reported effects of Hh pathway inhibitors at different levels of the immune response, from cytotoxic T cells to a modified local cytokines pattern. Given the specific relation between immune system and BCC development in some conditions, we will review BCC with focus on immune system changes mediated by Hh signaling pathway and induced by the inhibitors vismodegib and sonidegib in the treatment of BCC. Thus, we will give an overview of their effects on the local immune response, as well as a brief note on the supposed function of Hh pathway inhibition on the systemic one.

COVID-19 vaccination mimicking lymph-node progression in a patient with melanoma: a case report.

COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COVID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient's clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient's management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes.