BACKGROUND:Sentinel lymph node biopsy (SLNB) is one of the strongest prognostic indicators to date for cutaneous melanoma. However, its indication in elderly patients is controversial due to lower prognostic benefits, comorbidities, and surgical risks. OBJECTIVES:The aim of this study was to develop and validate a predictive model specifically tailored to patients aged ≥ 75 years with cutaneous melanoma, and to compare its performance with the Melanoma Institute Australia (MIA) and Memorial Sloan Kettering Cancer Center (MSKCC) calculators. METHODS:A multicenter, retrospective cohort study (SENTINOLD) including 795 patients aged ≥ 75 years was conducted across seven Spanish hospitals, representing one of the largest European datasets of elderly melanoma patients. A multivariable logistic regression model was developed using 12 clinicopathologic variables. Model performance was assessed by discrimination (AUC), calibration, and decision curve analysis (DCA), and compared with MIA and MSKCC calculators. Temporal validation was performed using a hold-out dataset representing the most recent diagnoses. RESULTS:The SENTINOLD nomogram demonstrated robust discrimination (AUC = 0.71), outperforming the MSKCC (0.66) and MIA (0.64) models (p < 0.05). Calibration and decision curve analysis confirmed greater clinical usefulness within the 5%-20% decision threshold range. Temporal validation showed stable performance (AUC = 0.68; Brier = 0.187). An interactive web-based calculator is freely available at https://sentinold.netlify.app, allowing clinicians to estimate the risk of SLN positivity using key tumor and patient characteristics. CONCLUSIONS:The SENTINOLD nomogram provides a reliable, user-friendly, and population-specific tool for individualized prediction of sentinel lymph node positivity in elderly melanoma patients. Its use may assist clinicians in guiding SLNB decision-making in this age group, although independent external validation and prospective evaluation of clinical impact are warranted.

Introduction: Complete lymph node dissection (CLND) was the standard practice for patients with melanoma and a positive sentinel lymph node biopsy (SLNB) until the results of two clinical trials published in 2016 and 2017 demonstrated that it did not improve melanoma-specific survival (MSS). However, it continues to be performed in some scenarios. No studies have ever been published on lymph node management after a positive SLNB in the routine clinical practice in our setting. Objectives: To determine the evolution of the indication for CLND in patients with a positive SLNB, as well as the characteristics associated with its performance. Material and methods: We conducted a multicenter retrospective observational study with patients with skin melanoma and positive sentinel lymph nodes diagnosed from 2017 through 2022 at 8 Spanish centers and 1 Italian center. Results: A total of 430 patients were included, 54% men, with 323 (75.1%) aged between 45 and 80 years. A total of 133 cases (31%) exhibited Breslow thickness >4 mm, 206 cases (49%) were ulcerated, and in 213 cases (55.7%), lymph node metastasis was >1 mm. Isolated lymphadenectomy or followed by adjuvant therapy was performed in 146 patients (34.1%). After multivariate logistic regression, the factors associated with the performance of CLND were the acral lentiginous melanoma histological subtype, lymph node metastasis size >1 mm, extracapsular spread, and the participant hospital. Age >80 years was inversely associated. Conclusion: While the frequency of CLND in patients with melanoma and positive SLNB has decreased, the indication for systemic adjuvant therapy in these patients has increased. However, CLND is still indicated in patients with high-risk characteristics. (c) 2024 AEDV. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

This retrospective case series compares vitiligo resulting from immune checkpoint inhibitor (ICI) therapy vs preexisting vitiligo among patients receiving ICI treatment for cancer.

Data regarding circulating tumor DNA (ctDNA) in stage III melanoma are scarce. The main objective was to analyze the usefulness of ctDNA determination in predicting tumor progression in patients with stage III melanoma. A prospective multicenter study was designed based on patients with stage III cutaneous melanoma. We studied BRAF , NRAS , and TERT promoter mutations in primary or metastatic tumors. Blood samples were collected after detecting a positive lymph node by sentinel lymph node biopsy; preoperative in patients with lymph node metastasis; or before any treatment in patients with confirmed unresectable lymph node metastasis or in-transit metastasis; 4 weeks after lymph node surgery (postoperative); and every 3 or 6 months after the baseline sample. From each sample, we isolated cell-free DNA, and previously identified mutations were searched for to identify ctDNA. ctDNA was detected in 21 (21/48, 43.8%) patients. Recurrence at a distant site and recurrence in two or more locations were associated with ctDNA detection at the time of recurrence ( P < 0.05). Plasma ctDNA detection at any time during follow-up was significantly associated with progression ( P = 0.011), overall mortality ( P < 0.001), and melanoma-specific death ( P < 0.001). We did not find an association between detectable ctDNA before surgery and disease progression; however, patients with detectable postsurgical ctDNA exhibited a lower recurrence-free survival, overall survival, and melanoma-specific survival. Prospective longitudinal blood sampling for the identification of ctDNA provides information regarding recurrence and survival.

Background: Acral melanoma is associated with poor prognosis. Studying the characteristics and prognosis of Caucasian patients is crucial to understand the distinct features of this tumor. Objectives: To analyze the epidemiological, clinicopathological, and prognostic features of acral melanoma in Caucasian patients. Methods: We conducted a retrospective, multicenter, cohort study of acral melanoma from a database across 20 hospitals from South Europe from January 2000 to December 2019. Results: A total of 733 acral melanomas were identified (median age, 67.5 years; 95.2%, Caucasians; 77.5% of which were located on the feet). Overall, 77.5% of cases were invasive melanomas. Foot melanomas had a higher proportion of invasive cases (80.8% vs 69.8%; p=0.003), stages III and IV at diagnosis (24.8% vs 11.7%; p<0.001), thicker Breslow depth (2.8mm vs 2.0mm; p=0.021) and a higher rate of positive sentinel lymph node biopsy (SLNB) (30.7% vs 15.7%; p=0.012). Thicker Breslow depth and later age of onset were risk factors for melanoma-specific survival. Thicker Breslow depth and ulceration were independent prognostic factors of relapse-free survival. Melanoma location and histopathological subtype were not associated with worse prognosis. Recurrences were a common finding (27.7%), with distant metastases appearing earlier than locoregional recurrences (1.32 years [IQR, 1.12-1.87] vs 2.14 years [IQR, 1.68-2.70]; p=0.015). Conclusion: This study, the largest in a predominantly Caucasian population, underscores the unfavorable outcomes of acral melanoma. Foot melanomas exhibited delayed detection, increased invasiveness, thicker Breslow depth, increased SLNB involvement, and higher AJCC stages. The high recurrence rate and early distant metastases emphasize the critical role of intensive follow-up and routine imaging modalities to detect asymptomatic relapses. (c) 2025 AEDV. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Therapeutic lymph node dissection has shown no clear benefits in terms of overall survival. However, appropriate regional control has repeatedly been reported in patients with lymph node metastasis. OBJECTIVE:The objective of the study was to analyze the outcomes of a conservative surgical approach to patients with melanoma and lymph node metastasis detected either clinically or by imaging tests. METHODS:A multicenter, prospective, longitudinal, single-arm cohort was conducted to recruit patients with melanoma who had 1-3 non-matted regional lymph node metastases (N1b, N2b) and were treated with conservative nodal surgery (conservative NS). The surgical procedure entailed resection of the metastatic lymph nodes identified, while preserving uninvolved lymph nodes in the regional basin. The patients received postoperative adjuvant immunotherapy according to routine clinical recommendations. The primary end-point was the 2-year regional lymph node recurrence-free survival (RRFS). RESULTS:A total of 25 patients with lymph node metastasis underwent conservative NS to remove inguinal (44.00%) and axillary (56.00%) lymph node metastasis. During the follow-up, 36.00% (n = 9) of the patients developed recurrence in the regional basin treated with conservative NS. The 2-year RRFS was 65.70% (95% CI 46.30%-85.10%), and MSS was 78.10% (95% CI 60.85%-95.35%) at 2 years. Stage IIIB patients exhibited no statistically significant improvement in 2-year RRFS (83.30%) (log-rank P = .238). The short-term surgical complications reported were seroma (32%, n = 8), hematoma (8%, n = 2), and wound infection (4%, n = 1). No cases of lymphedema were observed. CONCLUSION:Conservative NS has the potential to prevent unnecessary complete lymph node dissections, particularly in clinical settings where neoadjuvant immunotherapy is not a suitable first-line therapeutic option.

JDDG: Journal der Deutschen Dermatologischen GesellschaftEarly View CLINICAL LETTER SDRIFE and bullous reaction after treatment with enfortumab vedotin plus pembrolizumab: Case series Juan J. Lluch-Galcerá, Juan J. Lluch-Galcerá orcid.org/0000-0002-8373-4303 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorNerea Manzanares-Oliver, Nerea Manzanares-Oliver Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorManel Martinez-Molina, Manel Martinez-Molina orcid.org/0000-0002-1581-7895 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorLorena Valdivieso, Lorena Valdivieso orcid.org/0000-0003-4991-4543 Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, SpainSearch for more papers by this authorAram Boada, Aram Boada Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorSònia Segura, Sònia Segura orcid.org/0000-0003-0653-1382 Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorRoger Rovira, Roger Rovira Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorRamón M Pujol, Ramón M Pujol Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorAne Jaka, Corresponding Author Ane Jaka [email protected] orcid.org/0000-0003-2699-1159 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, Spain Correspondence Ane Jaka, MD, PhD, Department of Dermatology, Hospital Universitari Germans Trias i Pujol., C/ Carretera de Canyet, s/n, 08916 Badalona, Barcelona. Email: [email protected]Search for more papers by this author Juan J. Lluch-Galcerá, Juan J. Lluch-Galcerá orcid.org/0000-0002-8373-4303 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorNerea Manzanares-Oliver, Nerea Manzanares-Oliver Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorManel Martinez-Molina, Manel Martinez-Molina orcid.org/0000-0002-1581-7895 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorLorena Valdivieso, Lorena Valdivieso orcid.org/0000-0003-4991-4543 Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, SpainSearch for more papers by this authorAram Boada, Aram Boada Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, SpainSearch for more papers by this authorSònia Segura, Sònia Segura orcid.org/0000-0003-0653-1382 Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorRoger Rovira, Roger Rovira Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorRamón M Pujol, Ramón M Pujol Department of Dermatology, Hospital del Mar, Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB) and Universitat Pompeu Fabra (UPF), Barcelona, SpainSearch for more papers by this authorAne Jaka, Corresponding Author Ane Jaka [email protected] orcid.org/0000-0003-2699-1159 Department of Dermatology, Hospital Universitari Germans Trials i Pujol, Institut d'Investigació GermansTrias i Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Barcelona, Spain Correspondence Ane Jaka, MD, PhD, Department of Dermatology, Hospital Universitari Germans Trias i Pujol., C/ Carretera de Canyet, s/n, 08916 Badalona, Barcelona. Email: [email protected]Search for more papers by this author First published: 22 May 2024 https://doi.org/10.1111/ddg.15453 Juan J. Lluch-Galcerá and Nerea Manzanares-Oliver have equally contributed to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1Lacouture M, Patel A, Rosenberg J, et al. Management of Dermatologic Events Associated With the Nectin-4-directed Antibody-Drug Conjugate Enfortumab Vedotin. Oncologist. 2022; 27: e223-e232. 10.1093/oncolo/oyac001 PubMedWeb of Science®Google Scholar 2Penny C, Quow K, Rundle C, et al. Clinical and direct immunofluorescence characteristics of cutaneous toxicity associated with enfortumab vedotin. Br J Dermatol. 2022; 187: 126-127. 10.1111/bjd.21022 CASPubMedWeb of Science®Google Scholar 3Hirotsu KE, Rana J, Wang JY, et al. Clinicopathologic characterization of enfortumab vedotin-associated cutaneous toxicity in patients with urothelial carcinoma. J Am Acad Dermatol. 2021; 85(6): 1610-1611. 10.1016/j.jaad.2020.11.067 CASPubMedGoogle Scholar 4Dobry A, Virgen C, Hosking AM, et al. Cutaneous reactions with enfortumab vedotin: A case series and review of the literature. JAAD Case Rep. 2021; 14: 7-9. 10.1016/j.jdcr.2021.05.020 PubMedGoogle Scholar 5 World Health Organization. Vigiaccess.org [Internet]. Available from: https://www.vigiaccess.org [Last accessed January 24, 2024]. Google Scholar 6Buhl T, Forkel S. The flood of drug allergy cases. 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Background: Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. Objective: To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins >= 1 mm. Methods: Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. Results: In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). Limitations: Retrospective observational study based on pathology reports. Conclusion: Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.

Introducción: El melanoma presenta una incidencia creciente en España. Los estadios pronósticos de los pacientes con melanoma son determinados por diversos factores biológicos, como el grosor del tumor, la ulceración o la presencia de metástasis regionales o a distancia. La Academia Española de Dermatología y Venereología (AEDV) ha impulsado la creación de un Registro Español de Melanoma (REGESMEL) con el fin de evaluar otros factores de índole individual y relacionados con el Sistema Sanitario que pudieran influir en el pronóstico de los pacientes con melanoma. El objetivo del presente artículo es presentar REGESMEL y proporcionar datos descriptivos básicos correspondientes a su primer año de funcionamiento.Métodos: REGESMEL es una cohorte prospectiva multicéntrica de pacientes consecutivos con melanoma cutáneo invasivo que recoge datos demográficos y de estadificación, así como datos basales individuales y relacionados con la atención sanitaria. También registra el tratamiento médico y quirúrgico recibido.Resultados: Se incluyeron 450 casos de melanoma cutáneo invasivo procedentes de 19 centros participantes, detectando un predominio de melanomas finos con un grosor ≤1 mm (54,7%), localizados principalmente en el tronco posterior (35,2%). La biopsia selectiva del ganglio centinela se realizó en el 40,7% los casos. La mayoría de los casos de melanoma fueron sospechados por el propio paciente (30,4%) o por dermatólogos (29,6%). Los pacientes recibieron atención principalmente en centros sanitarios públicos (85,2%), empleándose algún recurso de teledermatología en el 21,6% de los casos.Conclusiones: La distribución de las variables patológicas y demográficas de los casos es consistente con los datos de otros estudios. REGESMEL cuenta ya con casos de 15 provincias españolas y dada su potencial representatividad convierte al Registro en una herramienta de importancia para abordar una amplia gama de preguntas de investigación.

Cutaneous squamous cell carcinoma (cSCC) is the second most common subtype of skin cancer. The scalp is one of the most frequently affected locations and is associated with a higher rate of complications, compared to other locations. In addition, it has a characteristic thickness and anatomical structure that may influence both growth pattern and treatment of primary cSCC; while clinical peripheral margins may be easily achieved during the surgery, vertical excision of the tumor is limited by the skull. Despite having a unique anatomy, current guidelines do not contemplate specific recommendations for scalp cSCC, which leads to inconsistent decision-making in multidisciplinary committees when discussing tumors with high risk factors or with close margins. This article provides specific recommendations for the management of patients with scalp cSCC, based on current evidence, as well as those aspects in which evidence is lacking, pointing out possible future lines of research. Topics addressed include epidemiology, clinical presentation and diagnosis, imaging techniques, surgical and radiation treatments, systemic therapy for advanced cases, and follow-up. The primary focus of this review is on management of primary cSCC of the scalp with localized disease, although where relevant, some points about recurrent cSCCs or advanced disease cases are also discussed.

Introducción La disección ganglionar completa (DGC) era la práctica estándar en pacientes con melanoma y biopsia selectiva del ganglio centinela (BSGC) positiva hasta que, en 2016 y 2017 se publicaron los resultados de dos ensayos clínicos que no demostraron que mejorase la supervivencia específica por melanoma (SEM). Sin embargo, continúa realizándose en algunos escenarios. No existen estudios que recojan el manejo ganglionar tras BSGC positivo en la práctica clínica en nuestro medio. Objetivos Determinar la evolución de la indicación de la DGC en pacientes con BSGC positiva, así como las características que se asocian a su realización. Material y métodos Estudio observacional retrospectivo multicéntrico que incluye pacientes con melanoma cutáneo y ganglio centinela positivo diagnosticados entre los años 2017-2022 en ocho centros españoles y uno italiano. Resultados Se incluyeron 430 pacientes, 54% hombres, 358 (75,1%) tenían entre 45-80 años, de ellos, 133 casos (31%) presentaban un Breslow>4mm, 206 casos (49,1%) estaban ulcerados, en 213 casos (55,7%) la metástasis ganglionar era>1mm. Se realizó la linfadenectomía aislada o seguida de adyuvancia en 146 pacientes (34,1%). Tras una regresión logística multivariante, los factores asociados a la realización de DGC fueron el subtipo histológico melanoma lentiginoso acral (MLA), un tamaño de metástasis ganglionar>1mm, la extensión extracapsular y el hospital participante. La edad>80 años se asoció inversamente. Conclusión Mientras que ha disminuido la frecuencia de realización de la DGC en pacientes con melanoma y BSGC positiva, ha aumentado la indicación del tratamiento sistémico adyuvante en estos pacientes. Sin embargo, se sigue indicando la DGC en pacientes con características de alto riesgo.

BackgroundTargeted therapies and immunotherapy are currently considered the mainstay first-line treatment for advanced BRAF-mutated melanoma. However, the impact of treatment (targeted therapy and immunotherapy) and the prognostic factors are still not clear.Material and methodsMedical records of 140 patients diagnosed with advanced melanoma between 2011 and 2021 were retrospectively reviewed to extract demographic, BRAF status, treatment, performance status, and survival data. ORR, PFS, and OS were compared between patients diagnosed with advanced melanoma and treated with first-line IT or BRAF/MEKi. The prognostic factors were assessed using Cox regression models.ResultsIn all patients and those treated with immunotherapy, we did not find any effect of BRAF status on ORR, PFS, or OS. In patients with BRAF-mutated melanoma, ORR was 43.8% vs. 70% (P=0.04), PFS was 19.2 vs. 11.5 months (p=0.22), and OS was 33.4 vs. 16.4 months for the immunotherapy and targeted therapy groups, respectively (P=0.04). ECOG, presence of brain metastases, and high LDH level from initiation of first-line treatment were all associated with differences in PFS and OS.ConclusionPatients with advanced BRAF-mutated melanoma treated with first-line immunotherapy had a significantly longer PFS and OS than those treated with first-line BRAF/MEKi; however, first-line BRAF/MEKi treatment had a significantly higher ORR than first-line immunotherapy.

RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.