EJC Skin Cancer最新文献

{"title":"Metastatic melanoma involving the uterine corpus: Diverse patterns of involvement and diagnostic pitfalls in a three-case series","authors":"Ludovica Pepe,&nbsp;Filippo Nozzoli,&nbsp;Lavinia Pugliese,&nbsp;Sandra von Borries,&nbsp;Andrea Carnevali,&nbsp;Priyadharsini Nagarajan,&nbsp;Daniela Massi","doi":"10.1016/j.ejcskn.2026.101164","DOIUrl":"10.1016/j.ejcskn.2026.101164","url":null,"abstract":"<div><div>Metastatic melanoma involving the uterine corpus is exceedingly rare and may mimic primary uterine malignancies, particularly when amelanotic or phenotypically divergent. We report three cases illustrating heterogeneous morphologic and immunophenotypic patterns: a poorly differentiated rhabdoid melanoma supported by molecular profiling; a melanoma of unknown primary presenting as multiple deeply pigmented uterine and pelvic deposits; and an intramyometrial spindled/epithelioid metastasis with loss of conventional melanocytic markers, in which <em>BRAF</em> p.V600E immunohistochemistry was diagnostically informative. These cases emphasize that accurate diagnosis requires integration of clinical history, morphology, immunohistochemistry, and molecular findings. An updated literature review was provided.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101164"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of combined BRAF-MEK inhibitor second-line therapy in patients with non-resectable or metastatic BRAFV600-positive melanoma after prior immunotherapy: A retrospective EUMelaReg multicenter study","authors":"Eva Ellebaek ,&nbsp;Michael Weichenthal ,&nbsp;Iva Gavrilova ,&nbsp;Nethanel Asher ,&nbsp;Patrick Terheyden ,&nbsp;Jochen Utikal ,&nbsp;Amina Jalovčić Suljeviić ,&nbsp;Claudia Pföhler ,&nbsp;Igor Stojkovski ,&nbsp;Rudolf Alexander Herbst ,&nbsp;Selma Ugurel ,&nbsp;Christina Ruhlmann ,&nbsp;Alfonso Berrocal ,&nbsp;Margarita Majem ,&nbsp;Branko Dujovic ,&nbsp;Viktor Šabarić ,&nbsp;Tomislav Duvancic ,&nbsp;Ainara Soria ,&nbsp;Marco Donia ,&nbsp;Henrik Schmidt ,&nbsp;Dirk Schadendorf","doi":"10.1016/j.ejcskn.2025.100773","DOIUrl":"10.1016/j.ejcskn.2025.100773","url":null,"abstract":"<div><h3>Background</h3><div>Randomised trials recently showed that sequencing of first-line (1 L) immune checkpoint inhibitor (ICI) and second-line (2 L) BRAF-MEK-inhibitor (BRAF/MEKi) combination therapy provides better clinical outcomes in <em>BRAF</em>^{<em>V600</em>}-mutated, irresectable/metastatic melanoma than the inverse sequence. However, efficacy benchmark data for 2 L BRAF/MEKi are limited as the combination was developed for 1 L use, lacking estimates for the impact of prior ICI.</div></div><div><h3>Methods</h3><div>This retrospectively study analysed 2343 patients from the EUMelaReg registry with <em>BRAF</em>^{<em>V600</em>}-mutated melanoma who received BRAF/MEKi either as 2 L after failing 1 L ICI (n = 654) or as 1 L treatment (n = 1689). Patients with prior adjuvant ICI or BRAF/MEKi were excluded. Prognostic imbalances between the two groups were adjusted using 1:1 inverse propensity score matching. Key efficacy outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and time on treatment (TOT).</div></div><div><h3>Results</h3><div>Patients in the 2 L cohort achieved outcomes from start of treatment at least equivalent to the matched 1 L BRAF/MEKi cohort. Kaplan-Meier estimates demonstrated longer median PFS (8.4 vs 7.7 months; p = 0.01) and longer median TOT (7.8 vs 6.2 months; p = 0.002) for patients treated with 2 L BRAF/MEKi compared to 1 L. Median OS from start of 2 L (17.2 months) or 1 L (16.0 months) BRAF/MEKi was similar (p = 0.73) despite inherent bias from differing index dates. ORR among both groups (56.4 % vs 53.5 %; p = 0.32) was equal.</div></div><div><h3>Conclusion</h3><div>This study further supports the recommended sequencing of ICI as 1 L and BRAF/MEKi as 2 L therapy for patients with <em>BRAF</em>^{<em>V600</em>}-mutated melanoma. It shows that prior failure of ICI does not compromise the efficacy of BRAF/MEKi treatment.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100773"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-center clinico-genomic analysis of KIT mutated melanomas and clinical outcomes with tyrosine kinase inhibitor treatment","authors":"Carl Maximilian Thielmann,&nbsp;Luisa Richter,&nbsp;Henry Karl Tapken,&nbsp;Johanna Andrea Seier,&nbsp;Lisa Schielke,&nbsp;Jan Sternberg,&nbsp;Julia Kretz,&nbsp;Inga Möller,&nbsp;Antje Sucker,&nbsp;Annette Paschen,&nbsp;Lennart Ocker-Serger,&nbsp;Frederik Krefting,&nbsp;Anne Zaremba,&nbsp;Lea Jessica Albrecht,&nbsp;Lisa Zimmer,&nbsp;Elisabeth Livingstone,&nbsp;Georg Lodde,&nbsp;Alpaslan Tasdogan,&nbsp;Jan-Malte Placke,&nbsp;Eva Hadaschik,&nbsp;Klaus Griewank","doi":"10.1016/j.ejcskn.2026.101152","DOIUrl":"10.1016/j.ejcskn.2026.101152","url":null,"abstract":"<div><h3>Background</h3><div><em>KIT</em> alterations occur in distinct melanoma subtypes, yet <em>KIT</em>-mutant melanoma remains clinically and biologically heterogeneous and lacks approved KIT-targeted therapy. We characterized clinico-genomic features of <em>KIT</em>-altered melanoma and described outcomes of patients treated with tyrosine kinase inhibitors (TKI).</div></div><div><h3>Methods</h3><div>In this retrospective cohort study, we reviewed 3837 next-generation sequencing (NGS) reports from the Department of Dermatology, University Hospital Essen (2013–2024) and identified 97 patients with <em>KIT</em>-mutated melanoma. Tumors were classified as <em>KIT</em> hotspot (activating, recurrent variants; n = 18) or non-hotspot (n = 79). Clinical characteristics, mutational landscape, number of detected mutations, UV-associated substitution patterns, and survival outcomes were analyzed; five <em>KIT</em>-mutant patients treated with TKIs were described in detail.</div></div><div><h3>Results</h3><div>Most cases were of cutaneous (82/97) origin, while other subgroups included mucosal (7/97) and melanoma of unknown primary (8/97). <em>KIT</em> hotspot mutations were enriched in acral and mucosal primaries and were mutually exclusive with <em>BRAF</em> V600 and <em>NRAS</em> Q61/G12 mutations, whereas non-hotspot tumors frequently harbored canonical drivers (<em>BRAF</em> V600 22.8%, <em>NRAS</em> Q61/G12 17.7%). <em>NF1</em> mutations were markedly enriched in non-hotspot tumors (62.0% vs 16.7%; p &lt; 0.001). In cutaneous melanoma, non-hotspot mutant tumors showed higher number of mutations than hotspot mutant tumors (median 13 vs 3; p &lt; 0.001) and a more pronounced UV mutation signature. Five patients received TKIs (imatinib, ripretinib, sunitinib, nilotinib) with responses ranging from mixed to complete responses.</div></div><div><h3>Conclusions</h3><div><em>KIT</em> hotspot and non-hotspot variants define biologically distinct subsets of <em>KIT</em>-altered melanoma. Non-hotspot <em>KIT</em> variants frequently co-occur with <em>NF1</em>-mutations and high-mutation numbers, supporting a passenger role in many cases, whereas hotspot <em>KIT</em> marks a targetable dependency and warrants repeat profiling at progression.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101152"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking locoregional therapy of Merkel cell carcinoma in the era of immune checkpoint inhibition","authors":"Jürgen C. Becker,&nbsp;Rogerio I. Neves,&nbsp;Piotr Rutkowski","doi":"10.1016/j.ejcskn.2026.101153","DOIUrl":"10.1016/j.ejcskn.2026.101153","url":null,"abstract":"<div><div>Merkel cell carcinoma (MCC) is a highly aggressive yet profoundly immunotherapy-sensitive skin cancer characterized by early nodal and systemic dissemination. Historically, aggressive locoregional treatment was considered essential because therapeutic options for advanced disease were limited. The advent of immune checkpoint inhibitors has fundamentally transformed outcomes in MCC and, for the first time, enabled critical reassessment of established surgical and radiotherapeutic paradigms. Contemporary evidence suggests that intensified locoregional therapy does not consistently improve survival, which appears to be driven primarily by occult systemic disease. Emerging perioperative immunotherapy data therefore support more individualized, biology-driven strategies, including potential de-escalation of local therapy in selected patients while maintaining effective oncologic control.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101153"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reponse to letter Re: Efficacy of combined BRAF-MEK inhibitor second-line therapy in patients with non-resectable or metastatic BRAFV600-positive melanoma after prior immunotherapy: A retrospective EUMelaReg multicenter study","authors":"Michael Weichenthal,&nbsp;Eva Ellebaek","doi":"10.1016/j.ejcskn.2026.101149","DOIUrl":"10.1016/j.ejcskn.2026.101149","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101149"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148587710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutropenia induced by dabrafenib and trametinib combination therapy in patients with melanoma: Incidence, risk factors and clinical implications","authors":"Jessica Fareau,&nbsp;Nausicaa Malissen,&nbsp;Sandrine Monestier,&nbsp;Florent Amatore,&nbsp;Anderson Loundou,&nbsp;Caroline Gaudy-Marqueste","doi":"10.1016/j.ejcskn.2026.101155","DOIUrl":"10.1016/j.ejcskn.2026.101155","url":null,"abstract":"<div><div>Neutropenia is a recognized but undercharacterized toxicity of dabrafenib/trametinib (D + T) combination therapy in melanoma. We conducted a retrospective single-center analysis of 171 patients treated with D + T between 2015 and 2020. Any-grade neutropenia occurred in 44 patients, predominantly within the first three months. Neutropenia was more frequent in women and in patients treated in the adjuvant setting. Most cases were mild and resolved spontaneously; dose reduction was required in 32% of affected patients. Infectious complications occurred in 13.6% of neutropenic patients, with three severe cases. Concomitant eosinopenia was observed in 50%, suggesting impairment of a shared myeloid progenitor via MAPK pathway inhibition.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101155"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From immune activation to pathological response: neoadjuvant immunotherapy in cutaneous squamous cell carcinoma. A systematic review and meta-analysis","authors":"Riccardo Gili,&nbsp;Monica Variolo,&nbsp;Fausto Petrelli,&nbsp;Massimiliano Nardone,&nbsp;Paolo Bossi,&nbsp;Carlo Resteghini","doi":"10.1016/j.ejcskn.2026.101156","DOIUrl":"10.1016/j.ejcskn.2026.101156","url":null,"abstract":"<div><h3>Background</h3><div>Cutaneous squamous cell carcinoma (cSCC) frequently arises in the head and neck region and is associated with significant morbidity when managed with extensive surgery and postoperative radiotherapy. Neoadjuvant immune checkpoint inhibitors (ICI) have emerged as a promising strategy to improve oncologic outcomes while enabling treatment de-escalation.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant ICI in locally advanced (LA) resectable cSCC. Literature from January 2020 to November 2025 was screened across major databases. Eligible prospective studies (≥20 patients) reporting pathological response were included. Pooled estimates of pathological responses were calculated using a random-effects model.</div></div><div><h3>Results</h3><div>Seven studies (eight cohorts; n = 270) were included. The pooled rate of combined clinical complete response (cCR), pathological complete response (pCR), and major pathological response (mPR) was 59.2% (95% CI: 53–65%). The pooled pCR rate was 45.7% (95% CI: 37.7–53.4%). Radiological assessment underestimated response compared to pathology by approximately 50%. Disease control was high, with progression rates ≤ 5%. Neoadjuvant ICI enabled omission or de-escalation of surgery and/or postoperative radiotherapy in a substantial proportion of responders, with encouraging survival outcomes. Treatment was well tolerated, with rare grade ≥ 3 adverse events and no significant surgical delays.</div></div><div><h3>Conclusions</h3><div>Neoadjuvant ICI demonstrates high pathological response rates and favorable safety in LA cSCC, supporting its role as a strategy for treatment de-intensification. Pathological response appears to be a reliable surrogate endpoint, whereas conventional imaging remains inadequate.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 101156"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148770016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Scalp Melanoma","authors":"R. Mukhamadiev","doi":"10.1016/j.ejcskn.2026.100804","DOIUrl":"10.1016/j.ejcskn.2026.100804","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100804"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147720255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of coagulopathy in patients with advanced skin cancer during treatment with immune checkpoint inhibitors","authors":"A. Kenyeres ,&nbsp;L. Soltész ,&nbsp;Z. Bereczky ,&nbsp;M. Nagy-Vincze ,&nbsp;I.L. Szabó ,&nbsp;G. Emri","doi":"10.1016/j.ejcskn.2026.100831","DOIUrl":"10.1016/j.ejcskn.2026.100831","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100831"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147720274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy switch after complete response to BRAF/MEK inhibitors in metastatic BRAF-mutant melanoma: a treatment-sparing, real-world cohort study","authors":"T.LE ROUX ,&nbsp;E. Desmedt ,&nbsp;C. Vuillamy ,&nbsp;S. Stien ,&nbsp;L. Mortier ,&nbsp;M. Boileau","doi":"10.1016/j.ejcskn.2026.100841","DOIUrl":"10.1016/j.ejcskn.2026.100841","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100841"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147720284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}