Department of Medical Oncology, School of Medicine, Faculty of Health Sciences, Aristotle University, Thessaloniki, Greece.
Oral and Maxillofacial Surgery, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Crit Rev Oncol Hematol. 2024 Oct;202:104458. doi: 10.1016/j.critrevonc.2024.104458. Epub 2024 Jul 27.
Melanoma metastasis to distant sites is associated with diminished survival rates and poor prognosis. Except of Breslow thickness and ulceration that are currently used in melanoma staging, the investigation of additional clinicopathological, dermatoscopic and molecular factors that could predict tumors with aggressive biologic behavior is of paramount importance.
A literature search was conducted in PubMed, Scopus, Cochrane databases and gray literature until November 2023. Observational studies (including cohorts and case-control studies) were included and clinical and histopathological factors of primary cutaneous melanomas, along with dermatoscopic and molecular predictors of distant metastasis (DM) and distant metastasis-free survival (DMFS) were assessed. Random - effect models were preferred, the results were presented as Hazard Ratios (HRs) with 95 %Confidence Intervals (CIs) and the I index quantified heterogeneity. Subgroup analysis according to AJCC stage and sensitivity analysis were also conducted.
One hundred forty-three and 101 studies were included in the qualitive and quantitative synthesis, respectively. Regarding clinical factors, males, compared to females, and head and neck location, compared to trunk, demonstrated higher risk for DM [n=36, HR 1.49, 95%CI 1.36 - 1.63, I 33% and n=21, HR 1.24, 95 %CI 1.01 - 1.52, I 62 %]. Both factors had similar effects on DMFS. Breslow thickness and ulceration were significant predictors or DM. Additional factors that posed an increased risk for DM were nodular (n=15, HR 2.51, 95 %CI 1.83 - 3.43, I 56 %) and lentigo maligna subtypes (n=12, HR 1.87, 95 %CI 1.27 - 2.75, I 0 %), compared to superficial spreading subtype, lymphovascular invasion (n=9, HR 2.05, 95 %CI 1.18 - 3.58, I 78 %), SLN positivity and BRAF+ mutational status. In contrast, regression was a negative predictor of DM (n=15, HR 0.59, 95 %CI 0.44 - 0.79, I 68 %). Two studies focused on dermatoscopic factors and found that low pigmentation and the presence of blue-white veil might predict DM development. The results of subgroup analysis for stage I-II patients were essentially similar and sensitivity analysis did not reveal significant alterations, despite the moderate or high heterogeneity in some categories.
Clinical and histological characteristics of the tumor along with dermatoscopic features and molecular parameters hold significant prognostic information and could be incorporated into models to predict melanomas with high metastatic potential.
黑色素瘤转移至远处部位与生存率降低和预后不良相关。除了目前用于黑色素瘤分期的 Breslow 厚度和溃疡外，研究其他可能预测具有侵袭性生物学行为的肿瘤的临床病理、皮肤镜和分子因素至关重要。
在 PubMed、Scopus、Cochrane 数据库和灰色文献中进行了文献检索，检索时间截至 2023 年 11 月。纳入观察性研究（包括队列研究和病例对照研究），评估原发性皮肤黑色素瘤的临床和组织病理学因素，以及远处转移（DM）和远处转移无复发生存（DMFS）的皮肤镜和分子预测因子。首选随机效应模型，结果以 95%置信区间（CI）的危害比（HR）表示，并用 I 指数量化异质性。还进行了根据 AJCC 分期的亚组分析和敏感性分析。
定性和定量综合分析分别纳入了 143 项和 101 项研究。关于临床因素，男性与女性相比，头颈部与躯干相比，发生 DM 的风险更高[分别有 36 项研究，HR 1.49，95%CI 1.36-1.63，I 33%和 21 项研究，HR 1.24，95%CI 1.01-1.52，I 62%]。这两个因素对 DMFS 均有相似的影响。Breslow 厚度和溃疡是 DM 的显著预测因子。其他增加 DM 风险的因素包括结节型（n=15，HR 2.51，95%CI 1.83-3.43，I 56%）和恶性雀斑样痣型（n=12，HR 1.87，95%CI 1.27-2.75，I 0%），与浅表扩散型相比，淋巴血管侵犯（n=9，HR 2.05，95%CI 1.18-3.58，I 78%）、SLN 阳性和 BRAF+突变状态。相比之下，消退是 DM 的阴性预测因子（n=15，HR 0.59，95%CI 0.44-0.79，I 68%）。两项研究关注皮肤镜因素，发现低色素沉着和蓝白面纱的存在可能预测 DM 的发生。对 I 期- II 期患者的亚组分析结果基本相似，尽管在某些类别中存在中度或高度异质性，但敏感性分析并未显示出显著变化。
肿瘤的临床和组织病理学特征，以及皮肤镜特征和分子参数具有重要的预后信息，可以纳入模型，以预测具有高转移潜能的黑色素瘤。
