Simon F Roy, Nnenna G Agim, Adnan Mir, Kasey L Couts, Travis Vandergriff, William A Robinson, Boris C Bastian, Ilona J Frieden, Iwei Yeh
Background: Large and giant congenital melanocytic naevi (CMN) present a risk for developing melanoma or neurocutaneous melanosis. Most CMN are caused by NRAS or, less commonly, BRAF mutations.
Objectives: To present a series of patients with large-to-giant CMN with BRAF fusion genes as driver alterations and describe their unique clinical presentation.
Methods: We retrospectively identified five patients, from three academic institutions, with giant CMN harbouring BRAF fusion genes. We analysed tumour DNA using capture-based next-generation sequencing.
Results: Four of five patients with giant CMN harbouring a BRAF fusion gene exhibited thousands of satellite naevi, many with significant pruritus, nodularity and firmness. One patient developed neurocutaneous melanosis. Histopathology showed marked stromal desmoplasia, akin to the changes observed in acquired melanocytic naevi with BRAF fusion genes. Notably, one patient responded to the MEK inhibitor trametinib, demonstrating the potential therapeutic advantage of genetic characterization of these lesions.
Conclusions: CMN with BRAF fusion genes appear to have unique clinical features and may be associated with numerous satellite lesions. Marked desmoplasia is a histopathological feature that can point to an underlying BRAF fusion gene.
{"title":"Congenital melanocytic naevi initiated by BRAF fusion oncogene with firmness, pruritus and desmoplastic stroma.","authors":"Simon F Roy, Nnenna G Agim, Adnan Mir, Kasey L Couts, Travis Vandergriff, William A Robinson, Boris C Bastian, Ilona J Frieden, Iwei Yeh","doi":"10.1093/bjd/ljaf061","DOIUrl":"10.1093/bjd/ljaf061","url":null,"abstract":"<p><strong>Background: </strong>Large and giant congenital melanocytic naevi (CMN) present a risk for developing melanoma or neurocutaneous melanosis. Most CMN are caused by NRAS or, less commonly, BRAF mutations.</p><p><strong>Objectives: </strong>To present a series of patients with large-to-giant CMN with BRAF fusion genes as driver alterations and describe their unique clinical presentation.</p><p><strong>Methods: </strong>We retrospectively identified five patients, from three academic institutions, with giant CMN harbouring BRAF fusion genes. We analysed tumour DNA using capture-based next-generation sequencing.</p><p><strong>Results: </strong>Four of five patients with giant CMN harbouring a BRAF fusion gene exhibited thousands of satellite naevi, many with significant pruritus, nodularity and firmness. One patient developed neurocutaneous melanosis. Histopathology showed marked stromal desmoplasia, akin to the changes observed in acquired melanocytic naevi with BRAF fusion genes. Notably, one patient responded to the MEK inhibitor trametinib, demonstrating the potential therapeutic advantage of genetic characterization of these lesions.</p><p><strong>Conclusions: </strong>CMN with BRAF fusion genes appear to have unique clinical features and may be associated with numerous satellite lesions. Marked desmoplasia is a histopathological feature that can point to an underlying BRAF fusion gene.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"232-239"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angelika Lackner, Teresa Burner, Marlene Huber, Saptaswa Dey, Stefan Aigner, Veronika Buxhofer-Ausch, Marija Geroldinger-Simic, Christoph Iselin, Yun-Tsan Chang, Yi-Chien Tsai, Sabine Altrichter, Peter Wolf, Susanne Kimeswenger, Emmanuella Guenova, Wolfram Hoetzenecker
Background: Despite novel therapeutic options, the long-term management of cutaneous T-cell lymphoma (CTCL) remains challenging. Extracorporeal photopheresis (ECP) is an immunomodulating photochemotherapy associated with higher overall survival when used for the treatment of leukaemic forms of CTCL. Its exact mode of action has not been fully elucidated. Immunogenic cell death (ICD) is pivotal in cancer immunotherapy, marked by the release of damage-associated molecular patterns that enhance dendritic cell (DC) maturation and cytotoxic T-lymphocyte responses.
Objectives: To explore ICD in patients with leukaemic forms of CTCL during ECP and its effect on DC activation.
Methods: We conducted in vitro studies with peripheral blood mononuclear cells (PBMCs) from healthy donors and ex vivo experiments with white blood cells (WBCs) from patients with leukaemic forms of CTCL undergoing ECP. We assessed cell viability, apoptosis and ICD markers [ATP, high mobility group box 1 protein (HMGB1), calreticulin] using flow cytometry, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Engulfment assays evaluated DC activation by ECP-treated CD4+ T cells.
Results: ECP-treated healthy PBMCs and WBCs from patients with leukaemic forms of CTCL showed a significant induction of ICD hallmarks, including ATP release, HMGB1 secretion and calreticulin surface exposure. In patients with leukaemic forms of CTCL, calreticulin exposure was mainly present in CD4+CD26- T cells, indicating greater ICD susceptibility of malignant T cells. ECP-treated CD4+ T cells were phagocytosed by DCs, a process that was found to be dependent on ICD signals.
Conclusions: ECP induces ICD in malignant T cells and, to a lesser extent, in healthy T cells, facilitates DC activation. These findings suggest that ECP enhances targeted immune responses against malignant T cells in leukaemic forms of CTCL, offering new insights into its therapeutic mechanisms and potential applications in cancer immunotherapy.
{"title":"Evidence of immunogenic cell death (ICD) and ICD-dependent dendritic cell activation induced by extracorporeal photopheresis in patients with leukaemic forms of cutaneous T-cell lymphoma.","authors":"Angelika Lackner, Teresa Burner, Marlene Huber, Saptaswa Dey, Stefan Aigner, Veronika Buxhofer-Ausch, Marija Geroldinger-Simic, Christoph Iselin, Yun-Tsan Chang, Yi-Chien Tsai, Sabine Altrichter, Peter Wolf, Susanne Kimeswenger, Emmanuella Guenova, Wolfram Hoetzenecker","doi":"10.1093/bjd/ljaf102","DOIUrl":"10.1093/bjd/ljaf102","url":null,"abstract":"<p><strong>Background: </strong>Despite novel therapeutic options, the long-term management of cutaneous T-cell lymphoma (CTCL) remains challenging. Extracorporeal photopheresis (ECP) is an immunomodulating photochemotherapy associated with higher overall survival when used for the treatment of leukaemic forms of CTCL. Its exact mode of action has not been fully elucidated. Immunogenic cell death (ICD) is pivotal in cancer immunotherapy, marked by the release of damage-associated molecular patterns that enhance dendritic cell (DC) maturation and cytotoxic T-lymphocyte responses.</p><p><strong>Objectives: </strong>To explore ICD in patients with leukaemic forms of CTCL during ECP and its effect on DC activation.</p><p><strong>Methods: </strong>We conducted in vitro studies with peripheral blood mononuclear cells (PBMCs) from healthy donors and ex vivo experiments with white blood cells (WBCs) from patients with leukaemic forms of CTCL undergoing ECP. We assessed cell viability, apoptosis and ICD markers [ATP, high mobility group box 1 protein (HMGB1), calreticulin] using flow cytometry, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Engulfment assays evaluated DC activation by ECP-treated CD4+ T cells.</p><p><strong>Results: </strong>ECP-treated healthy PBMCs and WBCs from patients with leukaemic forms of CTCL showed a significant induction of ICD hallmarks, including ATP release, HMGB1 secretion and calreticulin surface exposure. In patients with leukaemic forms of CTCL, calreticulin exposure was mainly present in CD4+CD26- T cells, indicating greater ICD susceptibility of malignant T cells. ECP-treated CD4+ T cells were phagocytosed by DCs, a process that was found to be dependent on ICD signals.</p><p><strong>Conclusions: </strong>ECP induces ICD in malignant T cells and, to a lesser extent, in healthy T cells, facilitates DC activation. These findings suggest that ECP enhances targeted immune responses against malignant T cells in leukaemic forms of CTCL, offering new insights into its therapeutic mechanisms and potential applications in cancer immunotherapy.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"276-286"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyungho Paik, Bo Ri Kim, Sang Woong Youn, Hyun Jeong Ju, Jung Min Bae, Chong Won Choi
{"title":"Performance of deep learning algorithm based on Xception in evaluating morphological characteristics reflecting the activity of vitiligo.","authors":"Kyungho Paik, Bo Ri Kim, Sang Woong Youn, Hyun Jeong Ju, Jung Min Bae, Chong Won Choi","doi":"10.1093/bjd/ljaf133","DOIUrl":"10.1093/bjd/ljaf133","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"328-329"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molly Wallace, Rishob Dasgupta, Karen Cravero, Henry Yang, Andrew P South, Neda Nikbakht
{"title":"The utility of collagen VII topical gene therapy in the treatment of surgical defect after excision of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma.","authors":"Molly Wallace, Rishob Dasgupta, Karen Cravero, Henry Yang, Andrew P South, Neda Nikbakht","doi":"10.1093/bjd/ljaf128","DOIUrl":"10.1093/bjd/ljaf128","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"337-339"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond universalis: eyebrow and eyelash loss in patients with alopecia areata.","authors":"Jennifer M Fu, Carolyn Goh","doi":"10.1093/bjd/ljaf139","DOIUrl":"10.1093/bjd/ljaf139","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"198"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhance the transparency in the development of the British Association of Dermatologists' living guidelines.","authors":"Hui Liu, Yuanyuan Yao, Yaolong Chen","doi":"10.1093/bjd/ljaf124","DOIUrl":"10.1093/bjd/ljaf124","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"348-349"},"PeriodicalIF":9.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tinea corporis at the injection site of interleukin-17 inhibitor in psoriasis vulgaris.","authors":"Keigo Takase, Takayoshi Komatsu-Fujii, Toshiaki Kogame, Atsushi Otsuka, Kenji Kabashima","doi":"10.1093/bjd/ljae511","DOIUrl":"10.1093/bjd/ljae511","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"351"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development and evaluation of novel and selective prolyl-tRNA synthetase inhibitor for keloid treatment: prospects and challenges.","authors":"Weimin Gao, Yihua Chen","doi":"10.1093/bjd/ljaf161","DOIUrl":"10.1093/bjd/ljaf161","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"201-202"},"PeriodicalIF":11.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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