{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:43:41Z","timestamp":1789425821006,"version":"build-2803163510"},"reference-count":46,"publisher":"Medical Journals Sweden AB","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Derm Venereol"],"abstract":"<jats:p>Cutaneous squamous cell carcinoma (cSCC) is a major complication of recessive dystrophic epidermolysis bullosa (RDEB) that has high morbidity and mortality rates and unmet therapeutic needs. The aim of this study was to evaluate the molecular pattern of cSCC and the clinical course of immunotherapy in 2 RDEB patients with multiple advanced cSCC. Clinical course and disease staging were evaluated retrospectively. The tumour tissues were subjected to immunohistochemical staining. DNA from the blood and cSCC samples was subjected to massive parallel sequencing, and somatic mutations were determined. Patient 1 survived for over 2 years as disease control was achieved with cemiplimab and intralesional interleukin-2. The target advanced cSCC demonstrated a high rate of somatic mutations and strong expression of the immune markers, indoleamine 2,3-dioxygenase, programmed cell death protein ligand 1, and lymphocyte-activation gene 3. The patient ultimately succumbed to complications of oesophageal carcinoma. Patient 2 had an undifferentiated cSCC on the foot, which displayed a low mutational burden and did not express immune markers. The tumour progressed quickly even with cemiplimab therapy. These 2 cases underscore the challenges of cSCC treatment for RDEB. Multiple tumours with different molecular and immune profiles occur concomitantly or sequentially, and surgical excision is not always possible because of the anatomical and tissue constraints imposed by the disease itself. In conclusion, programmed cell death protein 1 inhibitors are approved and effective in treating metastatic and locally advanced cSCC. Our experience and the literature suggest that cemiplimab is an option in patients with RDEB if surgery is not. Somatic mutations and the immune microenvironment should be characterized to predict therapeutic response, particularly in aggressive undifferentiated tumours.<\/jats:p>","DOI":"10.2340\/actadv.v103.4870","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T11:56:24Z","timestamp":1687262184000},"page":"adv4870","source":"Crossref","is-referenced-by-count":11,"title":["Variable Outcome of Immunotherapy in Advanced Multiple Cutaneous Squamous Cell Carcinomas in Two Patients with Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.2340","volume":"103","author":[{"given":"Laura","family":"Trefzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Scholten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Technau-Hafsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Meiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Has","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rafei-Shamsabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1183","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"33390","doi-asserted-by":"crossref","unstructured":"Fine J-D, Johnson LB, Weiner M, Li K-P, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: The National EB Registry experience, 1986-2006. J Am Acad Dermatol 2009; 60: 203-211.","DOI":"10.1016\/j.jaad.2008.09.035"},{"key":"33391","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1016\/j.jaad.2008.09.035","DOI":"10.1016\/j.jaad.2008.09.035"},{"key":"33392","doi-asserted-by":"crossref","unstructured":"Montaudi\u00e9 H, Chiaverini C, Sbidian E, Charlesworth A, Lacour J-P. Inherited epidermolysis bullosa and squamous cell carcinoma: a systematic review of 117 cases. Orphanet J Rare Dis 2016; 11: 117.","DOI":"10.1186\/s13023-016-0489-9"},{"key":"33393","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1186\/s13023-016-0489-9","DOI":"10.1186\/s13023-016-0489-9"},{"key":"33394","doi-asserted-by":"crossref","unstructured":"Mallipeddi R. Epidermolysis bullosa and cancer. Clin Exp Dermatol 2002; 27: 616-623.","DOI":"10.1046\/j.1365-2230.2002.01130.x"},{"key":"33395","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1046\/j.1365-2230.2002.01130.x","DOI":"10.1046\/j.1365-2230.2002.01130.x"},{"key":"33396","doi-asserted-by":"crossref","unstructured":"Cianfarani F, Zambruno G, Castiglia D, Odorisio T. Pathomechanisms of altered wound healing in recessive dystrophic epidermolysis bullosa. Am J Pathol 2017; 187: 1445-1453.","DOI":"10.1016\/j.ajpath.2017.03.003"},{"key":"33397","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1016\/j.ajpath.2017.03.003","DOI":"10.1016\/j.ajpath.2017.03.003"},{"key":"33398","doi-asserted-by":"crossref","unstructured":"Mellerio JE, Robertson SJ, Bernardis C, Diem A, Fine JD, George R, et al. Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines. Br J Dermatol 2016; 174: 56-67.","DOI":"10.1111\/bjd.14104"},{"key":"33399","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/bjd.14104","DOI":"10.1111\/bjd.14104"},{"key":"33400","doi-asserted-by":"crossref","unstructured":"Robertson SJ, Orrin E, Lakhan MK, O'Sullivan G, Felton J, Robson A, et al. Cutaneous squamous cell carcinoma in epidermolysis bullosa: a 28-year retrospective study. Acta Derm Venereol 2021; 101: adv00523.","DOI":"10.2340\/00015555-3875"},{"key":"33401","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.2340\/00015555-3875","DOI":"10.2340\/00015555-3875"},{"key":"33402","doi-asserted-by":"crossref","unstructured":"Harrs C, van den Akker PC, Baardman R, Duipmans JC, Horv\u00e1th B, van Kester MS, et al. The aggressive behaviour of squamous cell carcinoma in epidermolysis bullosa: analysis of clinical outcomes and tumour characteristics in the Dutch EB Registry. Br J Dermatol 2022; 187: 824-826.","DOI":"10.1111\/bjd.21769"},{"key":"33403","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/bjd.21769","DOI":"10.1111\/bjd.21769"},{"key":"33404","doi-asserted-by":"crossref","unstructured":"Sch\u00e4fer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 2008; 9: 628.","DOI":"10.1038\/nrm2455"},{"key":"33405","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1038\/nrm2455","DOI":"10.1038\/nrm2455"},{"key":"33406","doi-asserted-by":"crossref","unstructured":"Hoste E, Arwert EN, Lal R, South AP, Salas-Alanis JC, Murrell DF, et al. Innate sensing of microbial products promotes wound-induced skin cancer. Nat Commun 2015; 6: 5932.","DOI":"10.1038\/ncomms6932"},{"key":"33407","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1038\/ncomms6932","DOI":"10.1038\/ncomms6932"},{"key":"33408","doi-asserted-by":"crossref","unstructured":"Cho RJ, Alexandrov LB, den Breems NY, Atanasova VS, Farshchian M, Purdom E, Nguyen TN, et al. APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa. Sci Transl Med 2018; 10: eaas9668.","DOI":"10.1016\/j.jid.2017.07.734"},{"key":"33409","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1016\/j.jid.2017.07.734","DOI":"10.1016\/j.jid.2017.07.734"},{"key":"33410","doi-asserted-by":"crossref","unstructured":"Condorelli AG, Dellambra E, Logli E, Zambruno G, Castiglia D. Epidermolysis bullosa-associated squamous cell carcinoma: from pathogenesis to therapeutic perspectives. Int J Mol Sci 2019; 20: 5707.","DOI":"10.3390\/ijms20225707"},{"key":"33411","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.3390\/ijms20225707","DOI":"10.3390\/ijms20225707"},{"key":"33412","doi-asserted-by":"crossref","unstructured":"Reimer A, Lu S, He Y, Bruckner-Tuderman L, Technau-Hafsi K, Meiss F, et al. Combined anti-inflammatory and low-dose antiproliferative therapy for squamous cell carcinomas in recessive dystrophic epidermolysis bullosa. J Eur Acad Dermatol Venereol 2020; 34: e1-3.","DOI":"10.1111\/jdv.15835"},{"key":"33413","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/jdv.15835","DOI":"10.1111\/jdv.15835"},{"key":"33414","doi-asserted-by":"crossref","unstructured":"Kim M, Li M, Intong LR, Tran K, Melbourne W, Marucci D, et al. Use of cetuximab as an adjuvant agent to radiotherapy and surgery in recessive dystrophic epidermolysis bullosa with squamous cell carcinoma. Br J Dermatol 2013; 169: 208-210.","DOI":"10.1111\/bjd.12272"},{"key":"33415","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/bjd.12272","DOI":"10.1111\/bjd.12272"},{"key":"33416","doi-asserted-by":"crossref","unstructured":"Medek K, Koelblinger P, Koller J, Diem A, Ude-Schoder K, Bauer JW, Laimer M. Wundheilungsst\u00f6rungen w\u00e4hrend der antitumor\u00f6sen Therapie mit Cetuximab bei schwerer generalisierter dystropher Epidermolysis bullosa. J Dtsch Dermatol Ges J Ger Soc Dermatol 2019; 17: 448-450.","DOI":"10.1111\/ddg.13802_g"},{"key":"33417","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/ddg.13802_g","DOI":"10.1111\/ddg.13802_g"},{"key":"33418","doi-asserted-by":"crossref","unstructured":"Piccerillo A, El Hachem M, De Vito R, De Luca EV, Peris K. Pembrolizumab for treatment of a patient with multiple cutaneous squamous cell carcinomas and recessive dystrophic epidermolysis bullosa. JAMA Dermatol 2020; 156: 708-710.","DOI":"10.1001\/jamadermatol.2020.0304"},{"key":"33419","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1001\/jamadermatol.2020.0304","DOI":"10.1001\/jamadermatol.2020.0304"},{"key":"33420","doi-asserted-by":"crossref","unstructured":"Duong T, Wong D, Barrett A, Price H. Successful use of immunotherapy to treat advanced cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa. BMJ Case Rep 2021; 14: e238966.","DOI":"10.1136\/bcr-2020-238966"},{"key":"33421","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1136\/bcr-2020-238966","DOI":"10.1136\/bcr-2020-238966"},{"key":"33422","doi-asserted-by":"crossref","unstructured":"Schwieger-Briel A, Trefzer L, Schumann H, Reimer- Taschenbrecker A, Rafei-Shamsabadi D, Meiss F, Has C. Esophageal carcinoma in severe recessive dystrophic epidermolysis bullosa - an underestimated complication? J Eur Acad Dermatol Venereol 2022; 36: e293-e295.","DOI":"10.1111\/jdv.17826"},{"key":"33423","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/jdv.17826","DOI":"10.1111\/jdv.17826"},{"key":"33424","doi-asserted-by":"crossref","unstructured":"Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Guti\u00e9rrez E, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 2022; 386: 24-34.","DOI":"10.1056\/NEJMoa2109970"},{"key":"33425","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1056\/NEJMoa2109970","DOI":"10.1056\/NEJMoa2109970"},{"key":"33426","doi-asserted-by":"crossref","unstructured":"Obermannov\u00e1 R, Alsina M, Cervantes A, Leong T, Lordick F, Nilsson M, et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol 2022; 33: 992-1004.","DOI":"10.1016\/j.annonc.2022.07.003"},{"key":"33427","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1016\/j.annonc.2022.07.003","DOI":"10.1016\/j.annonc.2022.07.003"},{"key":"33428","doi-asserted-by":"crossref","unstructured":"Li Z, Sun G, Sun G, Cheng Y, Wu L, Wang Q, et al. Various uses of PD1\/PD-L1 inhibitor in oncology: opportunities and challenges. Front Oncol 2021; 11: 771335.","DOI":"10.3389\/fonc.2021.771335"},{"key":"33429","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.3389\/fonc.2021.771335","DOI":"10.3389\/fonc.2021.771335"},{"key":"33430","doi-asserted-by":"crossref","unstructured":"Khaddour K, Gorell ES, Dehdashti F, Tang JY, Ansstas G. Induced remission of metastatic squamous cell carcinoma with an immune checkpoint inhibitor in a patient with recessive dystrophic epidermolysis bullosa. Case Rep Oncol 2020; 13: 911-915.","DOI":"10.1159\/000508933"},{"key":"33431","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1159\/000508933","DOI":"10.1159\/000508933"},{"key":"33432","doi-asserted-by":"crossref","unstructured":"Robertson SJ, Orrin E, Lakhan MK, O'Sullivan G, Felton J, Robson A, et al. Cutaneous squamous cell carcinoma in epidermolysis bullosa: a 28-year retrospective study. Acta Derm Venereol 2021; 101: adv00523.","DOI":"10.2340\/00015555-3875"},{"key":"33433","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.2340\/00015555-3875","DOI":"10.2340\/00015555-3875"},{"key":"33434","doi-asserted-by":"crossref","unstructured":"Vasilev P, Kalev D, Karamanliev M, Dimitrov D, Troyanova P, Yordanova I. Cemiplimab treatment of squamous cell carcinoma in a patient with severe recessive dystrophic epidermolysis bullosa. J Dtsch Dermatol Ges 2023; 21: 295-297.","DOI":"10.1111\/ddg.14980"},{"key":"33435","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1111\/ddg.14980","DOI":"10.1111\/ddg.14980"}],"container-title":["Acta Dermato-Venereologica"],"original-title":[],"link":[{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/download\/4870\/19054","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/download\/4870\/19054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T11:56:36Z","timestamp":1687262196000},"score":1,"resource":{"primary":{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/view\/4870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,20]]},"references-count":46,"URL":"https:\/\/doi.org\/10.2340\/actadv.v103.4870","relation":{},"ISSN":["1651-2057","0001-5555"],"issn-type":[{"value":"1651-2057","type":"electronic"},{"value":"0001-5555","type":"print"}],"subject":[],"published":{"date-parts":[[2023,6,20]]}}}