Tchernev Georgi, Temelkova Ivanka
Medical Institute of Ministry of Interior (MVR), Department of Dermatology, Venereology and Dermatologic Surgery, General Skobelev Nr 79, Sofia, Bulgaria.
Onkoderma - Private Clinic for Dermatologic Surgery, General Skobelev 26, Sofia, Bulgaria.
Open Access Maced J Med Sci. 2018 Dec 18;6(12):2378-2380. doi: 10.3889/oamjms.2018.517. eCollection 2018 Dec 20.
Drug-induced carcinogenesis is a matter of huge popularity and the subject of in-depth research over the last few years. According to the literature, dopamine agonists and acetylsalicylic acid fall into the list of drugs likely to potentiate the development of cutaneous melanoma. However, according to recent data, widely used angiotensin receptor blockers (ARBs) for the treatment of arterial hypertension, also carry a risk of malignancy development. The content of probable carcinogens, such as NDMA or NDEA in the drug valsartan (ARBs), causes the product to be withdrawn from the market. Recent experimental data suggest that another angiotensin receptor blocker-losartan also stimulates cell adhesion and melanoma cell invasion.
We present a 70-year-old patient who has been on systemic therapy with a combined drug of amlodipine and valsartan since 2008 and only valsartan from 2015. Three years after the first intake of valsartan (2011), the patient developed a pigment lesion on the right arm. Approximately 2.5 years after doubling the dose of valsartan, the patient observed a progression in the size of the lesion, which was the cause of the dermatological examination and hospitalisation for surgical removal. The melanocytic lesion was removed by radical excision and a surgical field of 0.5 cm in all directions, followed by histological verification, which found the presence of cutaneous melanoma with a tumour thickness of 3 mm. A re-excision was planned with an additional surgical field of 1.5 cm in all directions combined with parallel removal of a draining lymph node.
The case is indicative of two things: 1) the possible triggering of melanoma within the systemic treatment with valsartan; and 2) the necessity for optimization of melanoma surgery within the one-step melanoma surgery, which in this case would result in a single surgical excision of the primary lesion, with an operational security field of 2 cm in all directions, along with the removal of a draining lymph node.
药物诱导的致癌作用在过去几年中备受关注且是深入研究的主题。根据文献，多巴胺激动剂和乙酰水杨酸属于可能促进皮肤黑色素瘤发展的药物清单。然而，根据最近的数据，广泛用于治疗动脉高血压的血管紧张素受体阻滞剂（ARB）也存在发生恶性肿瘤的风险。药物缬沙坦（ARB）中可能存在的致癌物，如NDMA或NDEA，导致该产品被撤出市场。最近的实验数据表明，另一种血管紧张素受体阻滞剂——氯沙坦也会刺激细胞黏附和黑色素瘤细胞侵袭。
我们介绍一位70岁的患者，自2008年起接受氨氯地平和缬沙坦联合药物的全身治疗，从2015年起仅服用缬沙坦。在首次服用缬沙坦（2011年）三年后，患者右臂出现色素沉着病变。在缬沙坦剂量加倍约2.5年后，患者发现病变大小有所进展，这促使其接受皮肤科检查并住院进行手术切除。通过根治性切除和向四周各扩大0.5 cm的手术切缘切除黑色素细胞病变，随后进行组织学验证，结果发现存在肿瘤厚度为3 mm的皮肤黑色素瘤。计划进行再次切除，向四周各扩大1.5 cm的手术切缘，并并行切除一个引流淋巴结。
该病例表明两点：1）缬沙坦全身治疗过程中可能引发黑色素瘤；2）在一期黑色素瘤手术中优化黑色素瘤手术的必要性，在本病例中，这将导致对原发性病变进行单次手术切除，手术安全切缘为向四周各2 cm，并切除一个引流淋巴结。
