Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline – Update 2022
Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignanci...
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| Vydáno v: | European journal of cancer (1990) Ročník 171; s. 203 - 231 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Oxford
Elsevier Ltd
01.08.2022
Elsevier Science Ltd Elsevier |
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| ISSN: | 0959-8049, 1879-0852, 1879-0852 |
| On-line přístup: | Získat plný text |
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| Abstract | Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection.
MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis.
For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.
•Major progress in the diagnosis of Merkel cell carcinoma by immunohistochemistry/molecular pathogenesis.•The management of primary tumour was mostly based on retrospective studies.•Breakthrough in advance disease management with the approval of immunotherapy. |
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| AbstractList | Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection.
MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis.
For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.
•Major progress in the diagnosis of Merkel cell carcinoma by immunohistochemistry/molecular pathogenesis.•The management of primary tumour was mostly based on retrospective studies.•Breakthrough in advance disease management with the approval of immunotherapy. Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials. Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials. |
| Author | Hoeller, Christoph Gauci, Marie-Léa Aristei, Cynthia Zalaudek, Iris Malvehy, Josep Saiag, Philippe Kelleners-Smeets, Nicole Dreno, Brigitte Vieira, Ricardo Blom, Astrid Lallas, Aimilios Hauschild, Axel Moreno-Ramirez, David van Akkooi, Alexander C.J. Pellacani, Giovanni Bataille, Veronique Stratigos, Alexander J. Gomes, Fabio Fargnoli, Maria C. Peris, Ketty Forsea, Ana M. Grob, Jean-Jacques Lebbé, Céleste Harwood, Catherine Becker, Jurgen C. Garbe, Claus Del Marmol, Veronique Kaufmann, Roland Lorigan, Paul |
| Author_xml | – sequence: 1 givenname: Marie-Léa surname: Gauci fullname: Gauci, Marie-Léa organization: Universite’ de Paris, INSERM U976, AP-HP, Dermatology Department, Saint Louis Hospital, Paris, France – sequence: 2 givenname: Cynthia surname: Aristei fullname: Aristei, Cynthia organization: Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia and Perugia General Hospital, Italy – sequence: 3 givenname: Jurgen C. orcidid: 0000-0001-9183-653X surname: Becker fullname: Becker, Jurgen C. organization: German Cancer Consortium (DKTK), Deutsches Krebsforschung Institut, Heidelberg, Germany – sequence: 4 givenname: Astrid surname: Blom fullname: Blom, Astrid organization: Department of General and Oncologic Dermatology, Ambroise-Pare’ Hospital, APHP, & EA 4340 “Biomarkers in Cancerology and Hemato-oncology”, UVSQ, Universite’ Paris-Saclay, Boulogne-Billancourt, France – sequence: 5 givenname: Veronique surname: Bataille fullname: Bataille, Veronique organization: Mount Vernon Cancer Centre, East and North NHS Trust, Northwood, UK – sequence: 6 givenname: Brigitte surname: Dreno fullname: Dreno, Brigitte organization: Dermatology Department, CHU Nantes, Université Nantes, CIC 1413, CRCINA Inserm U1232, Nantes, France – sequence: 7 givenname: Veronique surname: Del Marmol fullname: Del Marmol, Veronique organization: Department of Dermatology, University Hospital Erasme, Universite’ Libre de Bruxelles, Belgium – sequence: 8 givenname: Ana M. orcidid: 0000-0002-1007-7883 surname: Forsea fullname: Forsea, Ana M. organization: Carol Davila University of Medicine and Pharmacy Bucharest, Department of Oncologic Dermatology, Elias University Hospital Bucharest, Romania – sequence: 9 givenname: Maria C. orcidid: 0000-0002-7249-2556 surname: Fargnoli fullname: Fargnoli, Maria C. organization: Dermatology - Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy – sequence: 10 givenname: Jean-Jacques surname: Grob fullname: Grob, Jean-Jacques organization: Aix Marseille University, APHM Hospital, Marseille, France – sequence: 11 givenname: Fabio orcidid: 0000-0003-0922-2665 surname: Gomes fullname: Gomes, Fabio organization: Cancer Research UK Lung Cancer Centre of Excellence, The University of Manchester, Manchester, UK – sequence: 12 givenname: Axel orcidid: 0000-0002-1212-9587 surname: Hauschild fullname: Hauschild, Axel organization: Department of Dermatology, University Hospital (UKSH), Kiel, Germany – sequence: 13 givenname: Christoph surname: Hoeller fullname: Hoeller, Christoph organization: Department of Dermatology, Medical University of Vienna, Austria – sequence: 14 givenname: Catherine surname: Harwood fullname: Harwood, Catherine organization: Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK – sequence: 15 givenname: Nicole surname: Kelleners-Smeets fullname: Kelleners-Smeets, Nicole organization: Department of Dermatology, Maastricht University Medical Centreþ, GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands – sequence: 16 givenname: Roland surname: Kaufmann fullname: Kaufmann, Roland organization: Department of Dermatology, Venereology and Allergology, Frankfurt University Hospital, Frankfurt, Germany – sequence: 17 givenname: Aimilios orcidid: 0000-0002-7193-0964 surname: Lallas fullname: Lallas, Aimilios organization: First Department of Dermatology, Aristotle University, Thessaloniki, Greece – sequence: 18 givenname: Josep surname: Malvehy fullname: Malvehy, Josep organization: Dermatology Department of Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de Enfermedades Raras, Instituto Carlos III, Spain – sequence: 19 givenname: David surname: Moreno-Ramirez fullname: Moreno-Ramirez, David organization: Department of Medical-&-Surgical Dermatology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain – sequence: 20 givenname: Ketty surname: Peris fullname: Peris, Ketty organization: Institute of Dermatology, Universita’ Cattolica, Rome, Italy – sequence: 21 givenname: Giovanni orcidid: 0000-0002-7222-2951 surname: Pellacani fullname: Pellacani, Giovanni organization: Dermatology Unit, University of Modena and Reggio Emilia, Modena, Italy – sequence: 22 givenname: Philippe orcidid: 0000-0002-6500-3507 surname: Saiag fullname: Saiag, Philippe organization: Department of General and Oncologic Dermatology, Ambroise-Pare’ Hospital, APHP, & EA 4340 “Biomarkers in Cancerology and Hemato-oncology”, UVSQ, Universite’ Paris-Saclay, Boulogne-Billancourt, France – sequence: 23 givenname: Alexander J. surname: Stratigos fullname: Stratigos, Alexander J. organization: 1st Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece – sequence: 24 givenname: Ricardo surname: Vieira fullname: Vieira, Ricardo organization: Coimbra Hospital and Universitary Centre, Coimbra, Portugal – sequence: 25 givenname: Iris orcidid: 0000-0002-7878-4955 surname: Zalaudek fullname: Zalaudek, Iris organization: Department of Dermatology, University of Trieste, Italy – sequence: 26 givenname: Alexander C.J. surname: van Akkooi fullname: van Akkooi, Alexander C.J. organization: Department of Surgical Oncology, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, Netherlands – sequence: 27 givenname: Paul surname: Lorigan fullname: Lorigan, Paul organization: Department of Medical Oncology University of Manchester and the Christie NHS Foundation Trust, Manchester, UK – sequence: 28 givenname: Claus orcidid: 0000-0001-8530-780X surname: Garbe fullname: Garbe, Claus organization: Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany – sequence: 29 givenname: Céleste orcidid: 0000-0002-5854-7290 surname: Lebbé fullname: Lebbé, Céleste email: celeste.lebbe@aphp.fr organization: Universite’ de Paris, INSERM U976, AP-HP, Dermatology Department, Saint Louis Hospital, Paris, France |
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| Title | Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline – Update 2022 |
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