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2. Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions

Author

Barnhill, Raymond L, Elder, David E, Piepkorn, Michael W, Knezevich, Stevan R, Reisch, Lisa M, Eguchi, Megan M, Bastian, Boris C, Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus J, Carr, Richard, Cochran, Alistair, Cook, Martin G, Duncan, Lyn M, Elenitsas, Rosalie, de la Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander J, Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela, Parker, Douglas C, Schmidt, Birgitta, Shea, Christopher R, Scolyer, Richard A, Tetzlaff, Michael, Xu, Xiaowei, Yeh, Iwei, Zembowicz, Artur, and Elmore, Joann G

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Clinical Research, Cancer, Humans, Skin Neoplasms, Melanoma, Pathologists, Consensus, Health Facilities, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.ObjectiveTo revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).Evidence reviewPracticing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0.FindingsThe new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma.Conclusions and relevanceThe implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients.

Published
2023

5. Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Author

Cabrita, Rita, Lauss, Martin, Sanna, Adriana, Donia, Marco, Skaarup Larsen, Mathilde, Mitra, Shamik, and Johansson, Iva

Subjects
Immunotherapy -- Patient outcomes, Lymphoid tissue -- Physiological aspects, Melanoma -- Care and treatment -- Patient outcomes, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers.sup.1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota.sup.2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8.sup.+ T cells and CD20.sup.+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8.sup.+CD20.sup.+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7.sup.+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy. The co-occurrence of tumour-associated CD8.sup.+ T cells and CD20.sup.+ B cells, and the formation of tertiary lymphoid structures, are linked with improved survival in cohorts of patients with metastatic melanoma., Author(s): Rita Cabrita [sup.1] , Martin Lauss [sup.1] , Adriana Sanna [sup.1] , Marco Donia [sup.2] , Mathilde Skaarup Larsen [sup.3] , Shamik Mitra [sup.1] , Iva Johansson [sup.1] , [...]

Published
2020
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6. FIGURE 1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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7. Supplementary Table S3 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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8. Figure S1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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9. FIGURE 5 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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10. FIGURE 4 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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11. Data from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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12. FIGURE 2 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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13. FIGURE 3 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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14. FIGURE 6 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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15. Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, additional, Karlsson, Joakim, additional, Nilsson, Lisa M., additional, Bergqvist, Mattias, additional, Johansson, Iva, additional, Carneiro, Ana, additional, Helgadottir, Hildur, additional, Levin, Max, additional, Ullenhag, Gustav, additional, Ståhlberg, Anders, additional, Olofsson Bagge, Roger, additional, Nilsson, Jonas A., additional, and Ny, Lars, additional

Published
2023
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16. Figure S3 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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17. Supplementary Table S1 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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18. Data from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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19. Supplementary Methods, Figures 3-5 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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20. Supplementary Table 4 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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21. Supplementary Table 3 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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22. Supplementary Figure 2 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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23. Supplementary Table 2 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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24. Supplementary Figure 1 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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25. Supplementary Table 1 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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26. Supplementary Figure Legends 53 from Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, primary, Lauss, Martin, primary, Karlsson, Anna, primary, Måsbäck, Anna, primary, Johansson, Iva, primary, Bendahl, Pär-Ola, primary, Vallon-Christersson, Johan, primary, Törngren, Therese, primary, Ekedahl, Henrik, primary, Geisler, Jürgen, primary, Höglund, Mattias, primary, Ringnér, Markus, primary, Lundgren, Lotta, primary, Jirström, Karin, primary, Olsson, Håkan, primary, Ingvar, Christian, primary, Borg, Åke, primary, Tsao, Hensin, primary, and Jönsson, Göran, primary

Published
2023
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27. Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., Jespersen, Henrik, Karlsson, Joakim, Nilsson, Lisa M., Bergqvist, Mattias, Johansson, Iva, Carneiro, Ana, Helgadottir, Hildur, Levin, Max, Ullenhag, Gustav, Stahlberg, Anders, Bagge, Roger Olofsson, Nilsson, Jonas A., Ny, Lars, Sah, Vasu R., Jespersen, Henrik, Karlsson, Joakim, Nilsson, Lisa M., Bergqvist, Mattias, Johansson, Iva, Carneiro, Ana, Helgadottir, Hildur, Levin, Max, Ullenhag, Gustav, Stahlberg, Anders, Bagge, Roger Olofsson, Nilsson, Jonas A., and Ny, Lars

Abstract

Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble

Published
2023
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28. Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement

Author

Pathologie Pathologen staf, Cancer, Barnhill, Raymond L., Elder, David E., Piepkorn, Michael W., Knezevich, Stevan R., Reisch, Lisa M., Eguchi, Megan M., Bastian, Boris C., Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus J., Carr, Richard, Cochran, Alistair, Cook, Martin G., Duncan, Lyn M., Elenitsas, Rosalie, De La Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander J., Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela, Parker, Douglas C., Schmidt, Birgitta, Shea, Christopher R., Scolyer, Richard A., Tetzlaff, Michael, Xu, Xiaowei, Yeh, Iwei, Zembowicz, Artur, Elmore, Joann G., Pathologie Pathologen staf, Cancer, Barnhill, Raymond L., Elder, David E., Piepkorn, Michael W., Knezevich, Stevan R., Reisch, Lisa M., Eguchi, Megan M., Bastian, Boris C., Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus J., Carr, Richard, Cochran, Alistair, Cook, Martin G., Duncan, Lyn M., Elenitsas, Rosalie, De La Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander J., Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela, Parker, Douglas C., Schmidt, Birgitta, Shea, Christopher R., Scolyer, Richard A., Tetzlaff, Michael, Xu, Xiaowei, Yeh, Iwei, Zembowicz, Artur, and Elmore, Joann G.

Published
2023

29. Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement.

Author

Blokx, Willeke, Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus, Carr, Richard, Cochran, Alistair, Cook, Martin, Duncan, Lyn, Elenitsas, Rosalie, de la Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander, Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela, Parker, Douglas, Schmidt, Birgitta, Shea, Christopher, Scolyer, Richard, Tetzlaff, Michael, Xu, Xiaowei, Zembowicz, Artur, Elmore, Joann, Barnhill, Raymond, Elder, David, Piepkorn, Michael, Knezevich, Stevan, Reisch, Lisa, Eguchi, Megan, Bastian, Boris, Yeh, Iwei, Blokx, Willeke, Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus, Carr, Richard, Cochran, Alistair, Cook, Martin, Duncan, Lyn, Elenitsas, Rosalie, de la Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander, Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela, Parker, Douglas, Schmidt, Birgitta, Shea, Christopher, Scolyer, Richard, Tetzlaff, Michael, Xu, Xiaowei, Zembowicz, Artur, Elmore, Joann, Barnhill, Raymond, Elder, David, Piepkorn, Michael, Knezevich, Stevan, Reisch, Lisa, Eguchi, Megan, Bastian, Boris, and Yeh, Iwei

Abstract

IMPORTANCE: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. OBJECTIVE: To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). EVIDENCE REVIEW: Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. FINDINGS: The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. CONCLUSIONS AND RELEVANCE: The implementation of the newly revised MPATH-Dx version 2.0 schem

Published
2023

30. Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement

Author

Barnhill, Raymond L; https://orcid.org/0000-0001-8086-8544, Elder, David E, Piepkorn, Michael W, Knezevich, Stevan R, Reisch, Lisa M, Eguchi, Megan M, Bastian, Boris C, Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus J, Carr, Richard, Cochran, Alistair, Cook, Martin G, Duncan, Lyn M, Elenitsas, Rosalie, de la Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander J, Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela; https://orcid.org/0000-0002-2215-9958, Parker, Douglas C, Schmidt, Birgitta, Shea, Christopher R, Scolyer, Richard A, Tetzlaff, Michael, et al, Barnhill, Raymond L; https://orcid.org/0000-0001-8086-8544, Elder, David E, Piepkorn, Michael W, Knezevich, Stevan R, Reisch, Lisa M, Eguchi, Megan M, Bastian, Boris C, Blokx, Willeke, Bosenberg, Marcus, Busam, Klaus J, Carr, Richard, Cochran, Alistair, Cook, Martin G, Duncan, Lyn M, Elenitsas, Rosalie, de la Fouchardière, Arnaud, Gerami, Pedram, Johansson, Iva, Ko, Jennifer, Landman, Gilles, Lazar, Alexander J, Lowe, Lori, Massi, Daniela, Messina, Jane, Mihic-Probst, Daniela; https://orcid.org/0000-0002-2215-9958, Parker, Douglas C, Schmidt, Birgitta, Shea, Christopher R, Scolyer, Richard A, Tetzlaff, Michael, and et al

Abstract

IMPORTANCE A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. OBJECTIVE To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). EVIDENCE REVIEW Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. FINDINGS The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. CONCLUSIONS AND RELEVANCE The implementation of the newly revised MPATH-Dx version 2.0 schema int

Published
2023

31. Using a clinicopathologic and gene expression (CP-GEP) model to identify stage I-II melanoma patients at risk for disease relapse

Author

Mulder, Evalyn, primary, Johansson, Iva, additional, Grünhagen, Dirk, additional, Tempel, Dennie, additional, Rentroia-Pacheco, Barbara, additional, Dwarkasing, Jvalini, additional, Verver, Daniëlle, additional, Mooyaart, Antien, additional, van der Veldt, Astrid, additional, Nijsten, Tamar, additional, Verhoef, Cornelis, additional, Mattsson, Jan, additional, Ny, Lars, additional, Hollestein, Loes, additional, and Bagge, Roger Olofsson, additional

Published
2023
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32. Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease

Author

Moncrieff, Marc D., primary, Lo, Serigne N., additional, Scolyer, Richard A., additional, Heaton, Martin J., additional, Nobes, Jenny P., additional, Snelling, Andrew P., additional, Carr, Michael J., additional, Nessim, Carolyn, additional, Wade, Ryckie, additional, Peach, A. Howard, additional, Kisyova, Rumi, additional, Mason, Jennifer, additional, Wilson, Ewan D., additional, Nolan, Grant, additional, Pritchard Jones, Rowan, additional, Johansson, Iva, additional, Olofsson Bagge, Roger, additional, Wright, Lucie J., additional, Patel, Nakul G., additional, Sondak, Vernon K., additional, Thompson, John F., additional, and Zager, Jonathan S., additional

Published
2022
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33. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Author

Cabrita, Rita, Lauss, Martin, Sanna, Adriana, Donia, Marco, Skaarup Larsen, Mathilde, Mitra, Shamik, Johansson, Iva, Phung, Bengt, Harbst, Katja, Vallon-Christersson, Johan, van Schoiack, Alison, Lövgren, Kristina, Warren, Sarah, Jirström, Karin, Olsson, Håkan, Pietras, Kristian, Ingvar, Christian, Isaksson, Karolin, Schadendorf, Dirk, Schmidt, Henrik, Bastholt, Lars, Carneiro, Ana, Wargo, Jennifer A., Svane, Inge Marie, and Jönsson, Göran

Published
2020
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34. DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype

Author

Sanna, Adriana, primary, Phung, Bengt, additional, Mitra, Shamik, additional, Lauss, Martin, additional, Choi, Jiyeon, additional, Zhang, Tongwu, additional, Njauw, Ching-Ni, additional, Cordero, Eugenia, additional, Harbst, Katja, additional, Rosengren, Frida, additional, Cabrita, Rita, additional, Johansson, Iva, additional, Isaksson, Karolin, additional, Ingvar, Christian, additional, Carneiro, Ana, additional, Brown, Kevin, additional, Tsao, Hensin, additional, Andersson, My, additional, Pietras, Kristian, additional, and Jönsson, Göran, additional

Published
2022
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35. Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse

Author

Mulder, Evalyn E. A. P., primary, Johansson, Iva, additional, Grünhagen, Dirk J., additional, Tempel, Dennie, additional, Rentroia-Pacheco, Barbara, additional, Dwarkasing, Jvalini T., additional, Verver, Daniëlle, additional, Mooyaart, Antien L., additional, van der Veldt, Astrid A. M., additional, Wakkee, Marlies, additional, Nijsten, Tamar E. C., additional, Verhoef, Cornelis, additional, Mattsson, Jan, additional, Ny, Lars, additional, Hollestein, Loes M., additional, and Olofsson Bagge, Roger, additional

Published
2022
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36. Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse

Author

Mulder, Evalyn E.A.P., Johansson, Iva, Grünhagen, Dirk J., Tempel, Dennie, Rentroia-Pacheco, Barbara, Dwarkasing, Jvalini T., Verver, Daniëlle, Mooyaart, Antien L., van der Veldt, Astrid A.M., Wakkee, Marlies, Nijsten, Tamar E.C., Verhoef, Cornelis, Mattsson, Jan, Ny, Lars, Hollestein, Loes M., Bagge, Roger Olofsson, Mulder, Evalyn E.A.P., Johansson, Iva, Grünhagen, Dirk J., Tempel, Dennie, Rentroia-Pacheco, Barbara, Dwarkasing, Jvalini T., Verver, Daniëlle, Mooyaart, Antien L., van der Veldt, Astrid A.M., Wakkee, Marlies, Nijsten, Tamar E.C., Verhoef, Cornelis, Mattsson, Jan, Ny, Lars, Hollestein, Loes M., and Bagge, Roger Olofsson

Abstract

BACKGROUND: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I-II melanoma) is watchful waiting, while >40% of patients with stage IB-IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I-II melanoma at risk of disease relapse.METHODS: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (the Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only.RESULTS: In total, 535 patients (stage I-II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4-96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3-84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41-6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a 'low risk' of recurrence (96.8% 5-year RFS (95%CI 91.6-98.8), n = 130), 49% as 'intermediate risk' (88.4% 5-year RFS (95%CI 83.6-91.8), n = 261), and 26% as 'high risk' (61.1% 5-year RFS (95%CI 51.9-69.1), n = 137).CONCLUSION: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I-II melanoma into two groups differentiat

Published
2022

37. Tumor genetic heterogeneity analysis of chronic sun‐damaged melanoma

Author

Sanna, Adriana, Harbst, Katja, Johansson, Iva, Christensen, Gustav, Lauss, Martin, Mitra, Shamik, Rosengren, Frida, Häkkinen, Jari, Vallon‐Christersson, Johan, Olsson, Håkan, Ingvar, Åsa, Isaksson, Karolin, Ingvar, Christian, Nielsen, Kari, and Jönsson, Göran

Subjects
in situ, melanoma, chronic sun damage, Original Article, Original Articles, heterogeneity, invasive, neoplasms
Abstract

Chronic sun‐damaged (CSD) melanoma represents 10%–20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra‐tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra‐deep targeted sequencing of 40 cancer‐associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in‐transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma‐related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p 95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.

Published
2019

38. Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms

Author

Benton, Sarah, primary, Zhao, Jeffrey, additional, Zhang, Bin, additional, Bahrami, Armita, additional, Barnhill, Raymond L., additional, Busam, Klaus, additional, Cerroni, Lorenzo, additional, Cook, Martin G., additional, de la Fouchardière, Arnaud, additional, Elder, David E., additional, Johansson, Iva, additional, Landman, Gilles, additional, Lazar, Alexander, additional, LeBoit, Philip, additional, Lowe, Lori, additional, Massi, Daniela, additional, Duncan, Lyn M., additional, Messina, Jane, additional, Mihic-Probst, Daniela, additional, Mihm, Martin C., additional, Piepkorn, Michael W., additional, Schmidt, Birgitta, additional, Scolyer, Richard A., additional, Shea, Christopher R., additional, Tetzlaff, Michael T., additional, Tron, Victor A., additional, Xu, Xiaowei, additional, Yeh, Iwei, additional, Yun, Sook Jung, additional, Zembowicz, Artur, additional, and Gerami, Pedram, additional

Published
2021
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40. Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation

Author

Crescitelli, Rossella, primary, Lässer, Cecilia, additional, Jang, Su Chul, additional, Cvjetkovic, Aleksander, additional, Malmhäll, Carina, additional, Karimi, Nasibeh, additional, Höög, Johanna L., additional, Johansson, Iva, additional, Fuchs, Johannes, additional, Thorsell, Annika, additional, Gho, Yong Song, additional, Olofsson Bagge, R., additional, and Lötvall, Jan, additional

Published
2020
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41. Tumor genetic heterogeneity analysis of chronic sun‐damaged melanoma.

Author

Sanna, Adriana, Harbst, Katja, Johansson, Iva, Christensen, Gustav, Lauss, Martin, Mitra, Shamik, Rosengren, Frida, Häkkinen, Jari, Vallon‐Christersson, Johan, Olsson, Håkan, Ingvar, Åsa, Isaksson, Karolin, Ingvar, Christian, Nielsen, Kari, and Jönsson, Göran

Subjects
CYCLIN-dependent kinase inhibitor-2A, MELANOMA, GENETIC load, FISHER exact test, RNA sequencing, MULTIPLE tumors, SUNSHINE
Abstract

Chronic sun‐damaged (CSD) melanoma represents 10%–20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra‐tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra‐deep targeted sequencing of 40 cancer‐associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in‐transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma‐related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p <.01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma

Author

Harbst, Katja, primary, Staaf, Johan, additional, Lauss, Martin, additional, Karlsson, Anna, additional, Måsbäck, Anna, additional, Johansson, Iva, additional, Bendahl, Pär-Ola, additional, Vallon-Christersson, Johan, additional, Törngren, Therese, additional, Ekedahl, Henrik, additional, Geisler, Jürgen, additional, Höglund, Mattias, additional, Ringnér, Markus, additional, Lundgren, Lotta, additional, Jirström, Karin, additional, Olsson, Håkan, additional, Ingvar, Christian, additional, Borg, Åke, additional, Tsao, Hensin, additional, and Jönsson, Göran, additional

Published
2012
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44. Naevoid Malignant Melanoma: A Diagnosis of a Naevus That You Later Regret.

Author

THEODOSIOU, Grigorios, JOHANSSON, Iva, HAMNERIUS, Nils, and SVENSSON, Åke

Subjects
*TISSUE wounds, *HUMAN skin color, *KERATOSIS, *NEVUS, *MELANOMA
Abstract

The article presents a case study of 49-year-old man with lesion on the dorsal side of his left leg. Examinations revealed papillomatous lesion with pigmentation and to exhibit a typical verrucous appearance. Diagnosis of seborrhoeic keratosis, compound naevus and malignant melanoma was conducted and surgical excise of entire lesion was made.

Published
2017
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