PDF(Pubmed)
Abstract：
The 2018 WHO edition on the classification of cutaneous melanocytic tumors recognizes eight evolutionary pathways of melanoma and describes tumors of uncertain malignant potential for each. When histology and immunohistochemistry do not support a confident conclusion about its malignant potential, a window of diagnostic uncertainty is created. Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are highly specific for melanoma and can be used as an ancillary technique to acquire a higher level of confidence in the diagnosis. However, little is known about the cost-effectiveness of testing for TERTp mutations. The aims of this study were to determine how often knowledge of the TERTp mutation status contributed to the final diagnosis and to develop a micro-costing framework to calculate cost-effectiveness. A retrospective analysis of all cutaneous melanocytic lesions that were discussed in the Noord-Nederland Melanoma Panel from January 2021 to October 2022 was performed to identify the cases in which the preliminary histopathological diagnosis was uncertain regarding malignancy (ambiguous, likely benign, or likely malignant). For cases in which a TERTp mutation analysis was performed, the final diagnoses were collected, and it was determined whether this impacted the overall conclusion. A micro-costing framework was established to model the financial impact of introducing TERTp mutation analyses and subsequent clinical procedures. The study included 367 cases, of which 175 diagnoses of uncertain malignant potential were initially reported. TERTp mutation analysis was performed for 151/175 (86%). In 38% of these cases, a higher level of confidence regarding malignant potential was obtained. The implementation of TERTp mutation analyses for cutaneous melanocytic proliferations with uncertain malignant potential can narrow the window of diagnostic uncertainty. For the patient group with an initial uncertain diagnosis, the increased cost for molecular testing (86.145 €) was compensated by a reduced overall treatment cost (-122.304 €). A microsimulation model to determine the cost-effectiveness of TERTp mutation analysis projected an overall saving for the healthcare system.
摘要：
2018年世界卫生组织关于皮肤黑素细胞肿瘤分类的版本认识到黑色素瘤的八个进化途径，并描述了每个肿瘤的不确定的恶性潜力。当组织学和免疫组织化学不支持关于其恶性潜能的可靠结论时，创建了一个诊断不确定性窗口。端粒酶逆转录酶基因启动子（TERTp）的突变对黑色素瘤具有高度特异性，可用作辅助技术以获得更高的诊断置信度。然而,对TERTp突变检测的成本效益知之甚少.这项研究的目的是确定TERTp突变状态知识对最终诊断的贡献频率，并开发一个微观成本计算框架来计算成本效益。对2021年1月至2022年10月在Noord-Nederland黑色素瘤小组中讨论的所有皮肤黑色素细胞病变进行了回顾性分析，以确定初步组织病理学诊断不确定恶性肿瘤的病例（模棱两可，可能是良性的，或可能是恶性的)。对于进行TERTp突变分析的病例，收集了最终的诊断，并确定这是否影响了总体结论。建立了微观成本核算框架，以对引入TERTp突变分析和后续临床程序的财务影响进行建模。该研究包括367例，其中最初报告了175例不确定的恶性潜能的诊断。对151/175(86%)进行TERTp突变分析。在38%的案例中，获得了更高的恶性潜能置信度.对具有不确定恶性潜能的皮肤黑素细胞增殖进行TERTp突变分析可以缩小诊断不确定性的窗口。对于最初诊断不确定的患者组，分子检测费用的增加(86.145€)被整体治疗费用的降低(-122.304€)所弥补.用于确定TERTp突变分析的成本效益的微观模拟模型预测了医疗保健系统的总体节省。
