Dermatology: Practical and Conceptual Image Letter | Dermatol Pract Concept. 2025;15(1): 4642 1 Non-Melanoma Skin Cancer Aggravation in Polycythemia Vera: Triggered by Ruxolitinib and Silenced With an IFN/Cemiplimab Efterpi Zafiriou1, Emmanouil Karampinis1, Vasileios Papadopoulos3, Georgia Stefani2, Athanasios Kotsakis3, George Vassilopoulos2 1 Department of Dermatology, Faculty of Medicine, School of Health Sciences, University General Hospital of Larissa, University of Thessaly, Larissa, Greece 2 Department of Hematology, UHL, University of Thessaly Medical School, Larissa, Greece 3 Department of Oncology, University General Hospital of Larissa, Larissa, Greece Citation: Zafiriou E, Karampinis E, Papadopoulos V, Stefani G, Kotsakis A, Vassilopoulos G. Non-Melanoma Skin Cancer Aggravation in Polycythemia Vera: Triggered by Ruxolitinib and Silenced With an IFN/Cemiplimab. Dermatol Pract Concept. 2025;15(1): 4642. DOI: https://doi.org/10.5826/dpc.1501a4642 Accepted: October 20, 2024; Published: January 2025 Copyright: ©2024 Zafiriou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Efterpi Zafiriou, Department of Dermatology, Faculty of Medicine, School of Health Sciences, University General Hospital of Larissa, University of Thessaly, 41110 Larissa, Greece Email: zafevi@o365.uth.gr Case Presentation A patient with JAK2+ polycythemia vera (PV) was started on ruxolitinib after inadequate disease control with initial therapy, which was later increased to 20 mg twice daily. Two months later, the patient developed a large ulcerative nasal lesion, diagnosed as squamous cell carcinoma (SCC) (Figure 1). This lesion was a recurrence of a nasal epithe- lioma that had been surgically removed 30 months prior. Ruxolitinib was discontinued, and ropeginterferon alfa-2b was introduced. The patient achieved full hematological and clinical response with 350 mg ropeginterferon alfa-2b every 15 days. Cemiplimab was then added for the recurrent SCC, resulting in satisfactory lesion regression (Figure 1) without adverse effects probably due to the combined benefits of interferon and PD-1 inhibition. Teaching Point Ruxolitinib, a JAK-STAT pathway inhibitor, has been ap- proved for treating PV in patients who are intolerant or resistant to hydroxyurea. It effectively alleviates systemic symptoms, controls hematocrit counts, and reduces spleen volume. However, reports highlight a high incidence of aggres- sive non-melanoma skin cancers among ruxolitinib-treated 2 Image Letter | Dermatol Pract Concept. 2025;15(1): 4642 patients, with poor or moderate differentiation and elevated rates of recurrence, metastasis, and mortality [1]. Due to the additive therapeutic effectiveness of Interferon (IFN) and PD-1/PD-L1 inhibition across various cancer types and in particular in melanoma, anti-PD-1 treatment such as cemiplimab was considered as an additional treatment for this locally advanced and recurrent SCC [2]. Our case sup- ports the co-administration of an anti-PD-1 antagonist with IFN to control both SCC and PV in a patient with SCC ag- gravation following ruxolitinib exposure. References 1. Lin JQ, Li SQ, Li S, et al. A 10-year retrospective cohort study of ruxolitinib and association with nonmelanoma skin cancer in patients with polycythemia vera and myelofibrosis. J Am Acad Dermatol. 202;86(2):339-344. DOI: 10.1016/j.jaad.2021 .10.004. PMID: 34648874. 2. Razaghi A, Durand-Dubief M, Brusselaers N, Björnstedt M. Com- bining PD-1/PD-L1 blockade with type I interferon in cancer ther- apy. Front Immunol. 2023;14:1249330. DOI: 10.3389/fimmu .2023.1249330. PMID: 37691915. PMCID: PMC10484344. Figure 1. (A,B). Patient undergoing ruxolitinib treatment exhibited SCC progression, manifesting as a significant, ulcerated lesion on the nose tip, draining pus. (C,D). Following treatment, the lesion notably improved, with the cancerous mass diminishing and the lesion re-epithelializing. This transformation occurred after the fourth dose of cemiplimab (350 mg cemiplimab, every 3 weeks), alongside ongoing ropeginterferon α-2b therapy.