{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:10:38Z","timestamp":1778778638392,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the FANCA gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control.<\/jats:p>","DOI":"10.3390\/ijms27104366","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:27:56Z","timestamp":1778776076000},"page":"4366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Squamous Cell Carcinoma of the Skin in a Teenager with Fanconi Anemia: A Challenging Treatment"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-8863","authenticated-orcid":false,"given":"Ekaterina","family":"Zelenova","sequence":"first","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5911-553X","authenticated-orcid":false,"given":"Tatiana","family":"Belysheva","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-5917","authenticated-orcid":false,"given":"Kristina","family":"Orlova","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasily","family":"Grigorenko","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Semenova","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Sharapova","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yana","family":"Vishnevskaya","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-5071","authenticated-orcid":false,"given":"Igor","family":"Samoylenko","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2642-4202","authenticated-orcid":false,"given":"Tatiana","family":"Nasedkina","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-2365","authenticated-orcid":false,"given":"Timur","family":"Valiev","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"},{"name":"Department of Oncology, Sechenov First Moscow State Medical University, 119048 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Polyakov","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Varfolomeeva","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Woodward, E.R., and Meyer, S. (2021). Fanconi Anaemia, Childhood Cancer and the BRCA Genes. Genes, 12.","DOI":"10.3390\/genes12101520"},{"key":"ref_2","first-page":"257","article-title":"Familial infantile pernicious-like anemia (pernicious blood picture and constitution)","volume":"117","author":"Fanconi","year":"1927","journal-title":"Jahrb. F\u00fcr Kinderheilkd."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-de-Teresa, B., Rodr\u00edguez, A., and Frias, S. (2020). Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences. Genes, 11.","DOI":"10.20944\/preprints202011.0563.v2"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3109\/10409238.2010.502166","article-title":"The Fanconi anemia pathway and ICL repair: Implications for cancer therapy","volume":"45","author":"Wang","year":"2010","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1182\/blood-2002-05-1399","article-title":"A novel diagnostic screen for defects in the Fanconi anemia pathway","volume":"100","author":"Shimamura","year":"2002","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1182\/blood-2002-07-2170","article-title":"A 20-year perspective on the International Fanconi Anemia Registry (IFAR)","volume":"101","author":"Kutler","year":"2003","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1182\/blood.2023022751","article-title":"Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia","volume":"144","author":"Lum","year":"2024","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejmg.2015.11.013","article-title":"Fanconi anemia with biallelic FANCD1\/BRCA2 mutations\u2014Case report of a family with three affected children","volume":"59","author":"Svojgr","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Choi, J., and Jung, M. (2025). Head and Neck Cancer in Fanconi Anemia: Clinical Challenges and Molecular Insights into a DNA Repair Disorder. Cancers, 17.","DOI":"10.3390\/cancers17183046"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/MPH.0b013e318063ef14","article-title":"Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia","volume":"29","author":"Reinhard","year":"2007","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13706","DOI":"10.1111\/petr.13706","article-title":"Squamous cell carcinoma development in Fanconi anemia patients who underwent hematopoietic stem cell transplantation","volume":"24","author":"Anak","year":"2020","journal-title":"Pediatr. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.critrevonc.2018.02.013","article-title":"Oral cancer in Fanconi anemia: Review of 121 cases","volume":"125","author":"Furquim","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Work Group, Invited Reviewers, Kim, J.Y.S., Kozlow, J.H., Mittal, B., Moyer, J., Olenecki, T., and Rodgers, P. (2018). Guidelines of care for the management of cutaneous squamous cell carcinoma. J. Am. Acad. Dermatol., 78, 560\u2013578.","DOI":"10.1016\/j.jaad.2017.10.007"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1007\/s13555-025-01470-7","article-title":"A Comprehensive Narrative Review of the Challenges Surrounding Cutaneous SCC","volume":"15","author":"Beach","year":"2025","journal-title":"Dermatol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1080\/17512433.2019.1665026","article-title":"Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma","volume":"12","author":"Ahmed","year":"2019","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chedid, M.F., Tregnago, A.C., Riva, F., Prediger, L., Agarwal, A., and Mattei, J. (2025). Indications and Mechanisms of Action of the Main Treatment Modalities for Non-Melanoma Skin Cancer. Life, 15.","DOI":"10.3390\/life15091447"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08820538.2026.2629879","article-title":"Immune Checkpoint Inhibitors for the Treatment of Periorbital Non-Melanoma Skin Cancers","volume":"18","author":"Bineshfar","year":"2026","journal-title":"Semin. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xu, H., Huang, Y., Zhao, N., Hu, H., and Cao, D. (2025). Retrospective analysis of pembrolizumab-related adverse reactions and death outcomes based on the FAERS database. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14342-2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1182\/blood-2017-01-761346","article-title":"PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: High response rate but frequent GVHD","volume":"130","author":"Haverkos","year":"2017","journal-title":"Blood"},{"key":"ref_20","first-page":"e95448","article-title":"A Deadly Duet: Fanconi Anemia (FA) With Head and Neck Cancer","volume":"17","author":"Chaithanya","year":"2025","journal-title":"Cureus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/hed.25577","article-title":"Treatment modalities and outcomes of Fanconi anemia patients with head and neck squamous cell carcinoma: Series of 9 cases and review of the literature","volume":"41","author":"Beckham","year":"2019","journal-title":"Head Neck"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1158\/0008-5472.CAN-20-3309","article-title":"Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability","volume":"81","author":"Deng","year":"2021","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11912-021-01120-z","article-title":"Immunotherapy for Non-melanoma Skin Cancer","volume":"23","author":"Shalhout","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1200\/JCO.19.03357","article-title":"Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas","volume":"38","author":"Maubec","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Morecroft, R.A., Phillipps, J.S., Gou, L., Bhatt, A.A., Kim, S., Mohammadi, H., Dronca, R.S., Doonan, B., Chen, R., and Zhao, Y. (2025). Immunotherapy and Radiation for Clinical Perineural Invasion in Cutaneous Squamous Cell Carcinoma. Cancers, 17.","DOI":"10.3390\/cancers17243921"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhu, S., Wang, Y., Tang, J., and Cao, M. (2022). Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1074477"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s12032-025-02785-3","article-title":"Integration of immunotherapy and radiotherapy in a therapeutic algorithm for locally advanced squamous cell skin cancer","volume":"42","author":"Koukourakis","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101557","DOI":"10.1016\/j.iotech.2025.101557","article-title":"Adjuvant anti-PD-1 therapy in high-risk cutaneous squamous-cell carcinoma: Post hoc insights from the C-POST and KEYNOTE-630 studies","volume":"29","author":"Cavalieri","year":"2025","journal-title":"Immunooncol. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJMoa1805131","article-title":"PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma","volume":"379","author":"Migden","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E16","DOI":"10.1002\/hed.26395","article-title":"Successful use of a therapeutic trial of graduated volume and dose escalation for postoperative head and neck radiotherapy in a Fanconi anemia patient","volume":"42","author":"Lewis","year":"2020","journal-title":"Head Neck"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100430","DOI":"10.1016\/j.xocr.2022.100430","article-title":"Pembrolizumab for Fanconi anemia with advanced tongue cancer","volume":"23","author":"Nagano","year":"2022","journal-title":"Otolaryngol. 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