The importance of caregivers for patients with advanced basal cell carcinoma treated with hedgehog-pathway inhibitors: an observational prospective study.

Oral targeted therapy with hedgehog pathway inhibitors has revolutionized the standard of care for patients with advanced basal cell carcinoma (BCC). These patients are frail and elderly, have various comorbidities, and receive pharmacological polytherapy. Moreover, adverse events may have a significant impact on therapeutic adherence, which must be managed by the clinician. We evaluated the impact of caregivers on the treatment of patients with advanced BCC in terms of continuation of therapy over time. All patients included in this observational prospective study had histologically confirmed metastatic or locally advanced BCC (LaBCC) and were treated with hedgehog pathway inhibitors from January 2016 to December 2021 at the Department of Dermatology at the University of Florence, Italy. The collected patient data included: age, sex, BCC site and area of spread; number of cycles, dose, duration and tolerability of therapy; marital status (single, divorced, married/living with a partner, widow/widower); and information such as living with someone, and the presence of any caregivers. Of the 34 patients included, 33 had LaBCC and one metastatic BCC. There were 11 females (32.4%) and 23 males (67.6%). Patients who were married or living with a caregiver -tolerated therapy better than single patients who lived alone. Indeed, patients with married/live-in caregivers and/or those with an adequate caregiver experienced greater therapeutic adherence and tolerance of adverse events. Given the greater therapeutic adherence of patients with live-in caregivers as partners, it is essential to consider patients' marital status. It is advisable to involve the caregiver early on, and there should be a training discussion on the various possible adverse events and the best way to mitigate them. Therapeutic success is linked not only to patients being informed but also to training of caregivers.

Tolerance of sonidegib after intolerance of vismodegib-Experience in two patients with nevoid basal cell carcinoma syndrome (Gorlin syndrome).

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare genetic condition characterized by the early development of numerous cutaneous basal cell carcinomas (BCCs). Although most BCCs are surgically treated with total resection, some of the lesions may proceed to a locally advanced or metastatic stage. Systemic treatment with a hedgehog inhibitors (HHIs) such as Vismodegib or Sonidegib is indicated in this population. We report cases of two patients with confirmed diagnoses of NBCCS. Both patients had undergone multiple surgical excisions and had been treated with oral Vismodegib 150 mg/day for a locally advanced tumour. They both discontinued the therapy due to its specific adverse effects (AEs) and are now being treated with oral Sonidegib, which has had better tolerability and a complete response. The aims of this report was to demonstrate the efficacy of HHI treatment with Sonidegib in patients with NCBBS who had previously treated with Vismodegib but discontinued it because of its specific AEs. Our experience in two patients shows that Sonidegib can be considered in Gorlin patients intolerant but responding to Vismodegib.

Comment on Kesic et al. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers 2022, 14, 1822.

We have read with great interest the paper by Kesic, V. et al. entitled "Early Diagnostics of Vulvar Intraepithelial Neoplasia" [...].

Cutaneous immune-related adverse events and photodamaged skin in patients with metastatic melanoma: could nicotinamide be useful?

Cutaneous immune-related adverse events (irAEs) occur in more than one-third of patients treated with immune checkpoint inhibitors; they are often the first clinical manifestation, although they may occur months after initiation of therapy. We noticed that our patients usually have these cutaneous AEs on photodamaged skin. In fact, out of 19 patients being treated for metastatic melanoma, 8 (42%), all of whom had significant cutaneous actinic damage, developed cutaneous irAEs earlier and in a more serious form than those without such damage. Thus, we gave a high oral dose of nicotinamide (500 mg twice daily) to the patients with metastatic melanoma who had photodamaged skin, and continued this for the entire duration of the immunotherapy. The appearance of the first signs of cutaneous irAEs was 180 days after starting therapy in nicotinamide-treated patients, compared with 65 days for patients not treated with nicotinamide.

Porocarcinoma: an epidemiological, clinical, and dermoscopic 20-year study.

BACKGROUND: Porocarcinoma (PC) is a rare cutaneous adnexal tumor with a variable metastatic potential. Given the paucity of data, guidelines and specific recommendations for PC are not yet well-established. In this study, we evaluate the disease-specific characteristics and outcome of this rare and often underestimated tumor. MATERIALS AND METHOD: A retrospective study of the epidemiological, clinical, and dermoscopic characteristics among cases of histopathologically diagnosed PC, collected from the database of two skin cancer clinics in Italy (Firenze, Pistoia) from 2000 to 2020, was conducted. RESULTS: Among the 52 patients with 53 tumors, 31 were men (59.6%) and 21 were women (40.4%) with an age range of 49-96 years (median age 82 years). The most common locations were the head/neck region in men (34% in men vs. 17% in women) and the lower limb in women (17% in women vs. 9% in men). Forty-eight cases (91%) underwent local excision. Of these patients, two (4%) experienced local recurrence, and one (2%) developed a second PC on a different anatomical site 1 month after the primary tumor's excision. Lymph node metastases were present in three cases (6%). Two of them have been treated surgically with adjuvant radiotherapy (both are disease-free after a 2-year follow-up period), whereas the third case developed visceral metastases followed by PC-related death. CONCLUSIONS: This study, with 52 patients with 53 tumors covering a follow-up period of more than 5 years, shows a less aggressive behavior of PC with 4% local recurrence, 6% nodal metastases, and 2% mortality.

Atypical Spitz tumours: an epidemiological, clinical and dermoscopic multicentre study with 16 years of follow-up.

BACKGROUND: Atypical Spitz tumours (ASTs) are regarded as an intermediate category distinguished from prototypical Spitz naevus by presenting one or more atypical features and often by an uncertain malignant potential. Clinical and dermoscopic features may play a relevant role in the diagnostic approach. AIM: To evaluate the clinical and dermoscopic features of ASTs, and their evolution over time. METHODS: This was a descriptive, multicentre study of the clinical and dermoscopic characteristics of ASTs. Data on clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, complete lymph node dissection, and outcome were collected from the databases of four Italian Dermatology Units for the period 2004-2021. RESULTS: The study population consisted of 99 patients (62 female, 37 male) with a histologically confirmed diagnosis of AST, including age at presentation ranged from 2 to 70 years (mean 28.1 years, median 24 years). Of the 99 patients, 29 (29.3%) underwent sentinel lymph node biopsy, which showed evidence of micrometastases in three cases (10.3%); all three patients underwent complete lymph node dissection with no evidence of further metastasis. Considering the whole study population, the clinical outcome was excellent, as all of the patients have no evidence of recurrence or distant metastasis. The follow-up period ranged from 6 to 216 months (mean 81.6 months, median 78 months). In addition, we collected data on the clinical and dermoscopic features of 26 lesions. The most frequent dermoscopic pattern observed was the multicomponent pattern (34.6%), followed by homogeneous (26.9%) and nonspecific (23.2%). In 66.7% of amelanotic ASTs, we observed glomerular (coiled) vessels uniformly distributed within the entire lesion, without asymmetry. CONCLUSION: The results of our study with a long follow-up show no recurrence or distant metastases, confirming the good clinical outcome, even in the case of sentinel lymph node positivity. From a diagnostic point of view, our series identified a typical dermoscopic picture for amelanotic ASTs, with a glomerular vascular pattern throughout the lesion in the absence of other dermoscopic parameters, making the correct diagnosis possible.

Eruptive melanocytic nevi in a patient with amelanotic melanoma: a paraneoplastic phenomenon?

Eruptive melanocytic nevi (EMN) describes the sudden onset of cutaneous nevi over weeks or months. Such a clinical event is generally seen in young adult patients and may be related to several possible causes. We report here a case of EMN in an old male patient followed up for a thick amelanotic cutaneous melanoma. A few months after the eruption, multiple hepatic masses, diagnosed as melanoma metastasis, were detected. The presented case may suggest that EMN may be a paraneoplastic phenomenon of alert in patients being followed for melanoma or other malignancies.

Fluorescence-advanced videodermatoscopy (FAV) for the differential diagnosis of suspicious facial lesions: A single-centre experience with pattern analysis and histopathological correlation.

BACKGROUND: Fluorescence-advanced videodermatoscopy (FAV) is a new non-invasive high-resolution skin imaging technique to assess pigmented lesions in conjunction with the clinical examination and dermatoscopy. OBJECTIVES: This is the first prospective study to identify morphologic descriptors and standardized terminology to examine facial pigmented lesions using FAV. The objectives were to identify FAV indicators, which can assist physicians in diagnosing suspicious flat facial pigmented lesions. METHODS: Consecutive equivocal pigmented lesions were retrospective analysed. Histopathological examination was performed for all the lesions. The main cytomorphological and cytoarchitectural FAV features were described and correlated with histopathological characteristics. RESULTS: From January to October 2020, 21 consecutive clinically suspected pigmented lesions in 20 patients were analysed using dermatoscopy and FAV and then surgically excised. Histopathological examination identified lentigo maligna (LM), lentigo maligna melanoma (LMM), solar lentigo (SL), flat seborrheic keratosis (SK) and pigmented actinic keratosis (PAK). Thirteen malignant melanocytic lesions were removed (11 LM, 2 LMM), two were diagnosed as PAK, and the remaining six pigmented lesions were SL-SKs. With FAV, large ovoid pleomorphic and dendritic cells arranged in the intrafollicular disposition, are typical of most malignant melanocytic lesions (12/13, 92.3%). No benign lesions displayed these features. In dermatoscopy, this folliculotropism corresponded to the presence of an annular-granular pattern with slate grey dots that were aggregated asymmetrically around follicular openings. CONCLUSIONS: FAV features can provide an improved diagnostic approach in the differential diagnosis of flat pigmented facial lesions.

Treatment of Advanced Basal Cell Carcinoma with Hedgehog Pathway Inhibitors: A Multidisciplinary Expert Meeting.

Despite recent progress and the publishing of several clinical guidelines on the management of advanced basal cell carcinoma, there is still no comprehensive set of clinical guidelines addressing the complexity inherent to the use of Hedgehog pathway inhibitors in the treatment of advanced basal cell carcinoma in real-world clinical practice. To develop practical and valuable tools that help specialists improve the clinical management of these patients, we sought the opinion of expert physicians with extensive knowledge and experience in the treatment of advanced basal cell carcinoma.

An Ear with Multiple Vascular Lesions: Does Dermoscopy Offer Any Hints?

Cutaneous lesions of vascular origin are normally easily diagnosed, both clinically and dermoscopically. However, Kaposi's sarcoma can trigger difficulties in making a correct preoperative diagnosis. Although dermoscopic pictures are not pathognomonic for diagnosing Kaposi's sarcoma, dermoscopic analysis could be a useful complement to a differential diagnosis of nodular pigmented cutaneous lesions. Here, we discuss two clinical cases and analyze the primary dermoscopic features of Kaposi's sarcoma, evaluating the potential utility of this method for differential diagnosis.

Clinical and dermoscopic polymorphisms in agminated Spitz nevi: Ugly presentation but benign behavior.

Agminated Spitz nevi are an uncommon entity, and their management is challenging due not only the young age of the patients but also the tumor's uncertain malignant potential and the variability in the dermoscopic and clinical presentation. We report a case of a 6-year-old boy with multiple agminated Spitz nevi on a café au lait macule with different atypical clinical patterns and dermoscopic features.

Treatment of periocular advanced basal cell carcinoma with Hedgehog pathway inhibitors: A single-center study and a new dedicated therapeutic protocol.

The management of difficult-to-treat periocular basal cell carcinoma (BCC) becomes very challenging in cases of delayed diagnosis, leading to the development of locally advanced BCC. The aim of this study was to evaluate the outcomes of Hedgehog pathway inhibitors (vismodegib and sonidegib) treatment in patients affected by periocular locally advanced BCC. We focused on the common adverse events and their correlation with the administration schedule, to determine a management protocol specific for the periocular area. This observational prospective study included a single-center case series with patients who were histologically confirmed to have periocular or orbital locally advanced BCC, treated with Hedgehog pathway inhibitors. All patients benefitted in terms of regression or stabilization of the neoplasm. In the first months of treatment, the HPIs were well tolerated, and the first important side effects appeared after about 5 months of continuous use of the drug. These data could lead to a new type of therapeutic scheme where neoadjuvant therapy could be followed by pulse therapy as an adjuvant to surgery.