Primary Mucosal Melanoma: Clinical Experience from a Single Italian Center.

(1) Background: Mucosal melanoma (MM) is a rare tumor, accounting for about 1% of all diagnosed melanomas. The etiology and pathogenesis of this tumor are unknown. It is characterized by an aggressive phenotype with poor prognosis and a low response rate to approved treatments. (2) Methods: We retrospectively analyzed the clinical features, treatments and outcomes of patients diagnosed with MM from different sub-sites (head and neck, gynecological and gastro-intestinal region) between 2013 and 2023 at our Institute. Survival times were estimated with the Kaplan-Meier method. Multivariate Cox regression was used to test the independence of significant factors in univariate analysis. (3) Results: Twenty-five patients were included in this study; the disease was equally distributed among females and males. The median age at diagnosis was 74 years old. The majority had MM originating from the head and neck (56%), particularly from the nasal cavity. BRAF V600 mutations were detected in 16% of the study population, limited to gastro-intestinal and gynecological MM. At diagnosis, at least half the patients (52%) had the disease located also at distant sites. The median overall survival (OS) in the whole study population was 22 months, with a longer OS for patients diagnosed at an early stage (38 months, p < 0.001). Longer OSs were reported for head and neck MM compared to other anatomic regions (0.06). Surgery of the primary tumor and radiotherapy were performed in 64% and 36% of the study population, respectively. Radiotherapy was performed only in head and neck MM. At multivariate analysis, the single factor that showed a reduced hazard ratio for death was radiotherapy. (4) Conclusions: The overall survival of MM from different sub-sites treated at our Italian Institution was 22 months, with better outcomes for early-stage disease and head and neck MM. Performing radiotherapy may have a protective effect on OS for head and neck MM. New treatment strategies are urgently needed to improve the outcome in this disease.

Vitiligo-like leukoderma as an indicator of clinical response to immune checkpoint inhibitors in late-stage melanoma patients.

PURPOSE: Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis. METHODS: A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated. RESULTS: Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR : 0.23; 95% CI 0.11-0.44, p < 0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N = 153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR: 0.17; 95% CI 0.06-0.44). CONCLUSION: Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.

Integrated care pathways and the hub-and-spoke model for the management of non-melanoma skin cancer: A proposal of the Italian Association of Hospital Dermatologists (ADOI).

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to "a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period". The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

[The integrated care pathway for non melanoma skin cancer: the Istituto Dermopatico dell'Immacolata - IRCCS experience in Rome.] / Il percorso diagnostico-terapeutico e assistenziale nella gestione del paziente affetto da tumore cutaneo non melanocitario: l'esperienza dell'IDI - IRCCS di Roma.

The incidence of non-melanoma skin cancers (NMSC) is increasing worldwide and these skin cancers have become an important health issue. An integrated care pathway (ICP) is a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to help a patient with a specific condition. The aim of this paper is to define the ICP for patients affected by NMSC referring to the Istituto Dermopatico dell'Immacolata - IRCCS of Rome and Villa Paola, Italy. This ICP is multidisciplinary and included various specialists like dermatologist, oncologist, general surgeon, plastic surgeon, anatomopathologist, molecular biologist and epidemiologist. This ICP is based on the most recent acquisitions in the literature, referring in particular to the national (EADO and SIDEMAST) and international guidelines (EDF and NCCN). We firstly valued the current practice for patients affected by NMSC referring to our Institute to define the multidisciplinary process map. This process delineated the activities and the responsibilities performed during delivery of care to the patients and the potential problem areas or opportunities for improvements. Subsequently, we defined the final ICP process. This ICP of NMSC represents an innovative strategy to provide high quality healthcare. This allows to ensure all the necessary procedures for the patient, optimizing the "continuum" of care and the use of health services, and improving the organization of the Institute regarding an important health issue.

Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

Treatment-related side effects and quality of life in cancer patients.

BACKGROUND: Cancer leads to a complicated pattern of change in quality of life (QoL). OBJECTIVE: The aims of this study were to assess the impact of treatment-related side effects on QoL in cancer patients and to explore which other factors, and to what extent, contribute to explain low QoL scores. METHODS: One hundred twenty-three cancer patients receiving chemotherapy completed the self-administered questionnaires (Medical Outcomes Short-Form-36 (SF-36) and 12-item General Health Questionnaire). Multiple regression analyses were conducted with the SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) scores as the dependent variables and demographic and clinical factors as independent variables. RESULTS: Seventy-two percent of patients experienced treatment-related side effects, and 32% resulted positive for psychiatric diseases. Two multivariate analyses showed that worse PCS scores, like worse MCS scores, were significantly and independently predicted by treatment-related side effects (odds ratio (OR) = 5.00, 95%CI 1.29-19.45; OR = 8.08, 95%CI 2.03-32.22, respectively) and changes in health over the last 12 months (OR =2.34, 95%CI 1.47-3.76; OR = 3.21, 95%CI 1.90-5.41, respectively), after adjustment for age, gender, years of school, time from cancer diagnosis, and psychiatric disease. CONCLUSIONS: Given the new emphasis on QoL, we suggest that physicians have a responsibility to openly discuss therapy efficacy, prognosis as well as the potential for adverse events with their patients. Changes in health, as perceived by patient, should also be monitored at follow-up.

Intradermal lymphoscintigraphy at rest and after exercise: a new technique for the functional assessment of the lymphatic system in patients with lymphoedema.

AIM: The aim of this study was to evaluate the effect of implementing a new technique, intradermal injection lymphoscintigraphy, at rest and after muscular exercise on the functional assessment of the lymphatic system in a group of patients with delayed or absent lymph drainage. METHODS: We selected 44 patients (32 women and 12 men; 15 of 44 with upper limb and 29 of 44 with lower limb lymphoedema). Thirty of 44 patients had bilateral limb lymphoedema and 14 of 44 had unilateral disease; 14 contralateral normal limbs were used as controls. Twenty-three patients had secondary lymphoedema after lymphadenectomy and the remaining 21 had idiopathic lymphoedema. Each of the 44 patients was injected with 50 MBq (0.3-0.4 ml) of (99m)Tc-albumin-nanocolloid, which was administered intradermally at the first interdigital space of the affected limb. Two planar static scans were performed using a low-energy general-purpose collimator (acquisition matrix 128 x 128, anterior and posterior views for 5 min), and in which drainage was slow or absent, patients were asked to walk or exercise for 2 min. A postexercise scan was then performed to monitor and record the tracer pathway and the tracer appearance time (TAT) in the inguinal or axillary lymph nodes. RESULTS: The postexercise scans showed that (i) 21 limbs (15 lower and six upper limbs) had accelerated tracer drainage and tracer uptake in the inguinal and/or axillary lymph nodes. Two-thirds of these showed lymph stagnation points; (ii) 27 limbs had collateral lymph drainage pathways; (iii) in 11 limbs, there was lymph drainage into the deeper lymphatic channels, with unusual uptake in the popliteal or antecubital lymph nodes; (iv) six limbs had dermal backflow; (v) three limbs did not show lymph drainage (TAT=not applicable). TAT=15 + or - 3 min, ranging from 12 to 32 min in limbs with lymphoedema versus 5 + or - 2 min, ranging from 1 to 12 min in the contralateral normal limbs (P<0.001). CONCLUSION: Intradermal injection lymphoscintigraphy gives a better imaging of the lymph drainage pathways in a shorter time, including cases with advanced lymphoedema. In some patients with lymphoedema, a 2-min exercise can accelerate tracer drainage, showing several compensatory mechanisms of lymph drainage. The effect of the exercise technique on TAT and lymphoscintigraphy findings could result in a more accurate functional assessment of lymphoedema patients.