Giant pedunculated mushroom-like cutaneous melanoma during systemic administration with nebivolol – phototoxicity and photocarcinogenicity mediated through the nitroso contamination in pharmaceuticals as possible new pathogenetic explanation
Medical Review (Med. pregled), 2026, 62(1), 57-62.
G. Tchernev1,2, V. Broshtilova3, K. G. Tchernev Jr1, D. S. Krastev4,5, N. S. Krastev3,6, S. Kordeva1, R. Hasegawa1
1Onkoderma – Clinic for Dermatology, Venereology and Dermatologic Surgery – Sofia
2Department of Dermatology and Venereology, Medical Institute of Ministry of Interior – Sofia
3Faculty of Medicine, Sofia University “Sv. Kl. Ohridski”
4College of Medicine “Yordanka Filaretova”, Medical University – Sofia
5Department of Anatomy and Physiology, South-West University “Neofit Rilski” – Blagoevgrad
6Department of Anatomy, Faculty of Medicine, Medical University – Sofia
Abstract: Paradoxically, as much as the positive role of beta-blockers in cutaneous melanoma patients has been recommended and advertised, the prognosis of this collective remains largely unchanged. Starting from these contradictory and rather limited in vision, one-sided observations, it might be appropriate to also address the following new or ʺnew-oldʺ, current, available but also somewhat forgotten circumstances: 1) the number of cutaneous melanomas identified to date and after beta-blocker administration worldwide is huge, and scientific data regarding this sensitive topic or relation remain sporadically published and thematized; 2) there is a lack of data on patients with advanced melanomas who healed after beta-blocker administration; 3) many beta-blockers are phototoxic and subsequently photocarcinogenic, which has been known for decades or even before nitrosamine contamination became officially known in 2018; 4) beta blockers are described in the FDA list as potentially/actually contaminated with nitrosamines; 5) nitrosamines are photocarcinogens by nature – a fact known for decades, and 6) the daily number of cutaneous melano-mas identified after or during beta-blocker intake increased exponentially. We report an interesting case in the world literature of a giant pedunculated metastatic melanoma arising from a congenital melanocytic nevus during treatment with nebivolol. We comment on the possible role of drug-mediated nitrosogenesis/photonitrosocarcinogenesis, which could be potentially key in defining two other important concepts related to melanoma incidence, namely: phototoxicity and photocarcinogenicity of the drugs taken. The overlap between the lists of drugs declared by the FDA to be contaminated with nitrosamines/photocarcinogens with those of phototoxic drugs worldwide (known even before nitrosamine contamination) could be a key point or a significant contributing factor in deciphering the pathogenesis of skin cancer, and melanoma in particular.
Key words: nitrosamines, nebivolol, phototoxicity, photocarcinogenicity, drug related nitrosogen-esis, photonitrosocarcinogenesis, pharmacooncogenesis, oncopharmacogenesis, nebivolol
Address for correspondence: Prof. Georgi Tchernev, MD, e-mail: georgi_tchernev@yahoo.de