Ricci Costantino, Dika Emi, Lambertini Martina, Ambrosi Francesca, Grillini Marco, Chillotti Stefano, Corradini Angelo Gianluca, Veronesi Giulia, Fiorentino Michelangelo, Corti Barbara
Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
Pathol Res Pract. 2022 May;233:153876. doi: 10.1016/j.prp.2022.153876. Epub 2022 Apr 1.
Lymphovascular invasion (LVI) is considered an unfavorable prognostic factor in cutaneous melanoma (CM). However, its detection by hematoxylin and eosin (H&E) is challenging, with discordant data about its association with clinical-pathological features and no previous studies investigating the inter- (IrOA) and intra-observer (IaOA) agreement. Herein, we tested H&E and double staining (DS) for CD34/SOX10 to detect the LVI in a cohort of 92 CMs, evaluating the IrOA, the IaOA, and the association with the other clinical-pathological features.
Five authors independently evaluated 92 consecutive and retrospectively enrolled cases of CMs. We assessed the IrOA (Fleiss's Kappa/FK and intraclass correlation coefficient/ICC) and the IaOA (Cohen's Kappa/CK) with both H&E and CD34/SOX10. Furthermore, we compared the LVI assessment with the two stains and analyzed the association with other clinical-pathological features [χ tests for dichotomous and categorical data; Student t-test (normal distribution) and Mann-Whitney U-test (non-normal distribution) for continuous data].
The IrOA was almost identical with H&E (FK=0.446; ICC=0.805) and CD34/SOX10 (FK=0.454; ICC=0.810); by contrast, the IaOA was higher with H&E for one pathologist (CK: 0.809) and with CD34/SOX10 for the other one (CK: 0.563). Applying previously defined criteria, LVI was detected in 10 (9.2%) and 11 (10.1%) cases with H&E and CD34/SOX10, respectively (p = 1.000). Both H&E and CD34/SOX10 were significantly associated with vertical growth phase (H&E, p: 0.014; CD34/SOX10, p: 0.010), mitosis ≥ 1/mm2 (H&E, p: 0.000; CD34/SOX10, p: 0.004), pT (H&E, p: 0.000; CD34/SOX10, p: 0.001), Breslow thickness (H&E, p: 0.000; CD34/SOX10, p: 0.001), and lymph node and/or distant metastasis (H&E, p: 0.005; CD34/SOX10, p: 0.000); only H&E was associated with ulceration (p: 0.002) and distant metastasis (p: 0.000), conversely, only CD34/SOX10 was associated with lymph node metastasis (p: 0.003).
CD34/SOX10 does not improve the IrOA and the IaOA of the LVI assessment in CM; furthermore, H&E and CD34/SOX10 show a similar profile of association with the other unfavorable clinical-pathological features of CM. As result, CD34/SOX10 could be a redundant diagnostic tool if applied for the prognostic characterization of not-selected CM in a routine diagnostic scenario.
淋巴管浸润（LVI）被认为是皮肤黑色素瘤（CM）的一个不良预后因素。然而，通过苏木精和伊红（H&E）染色检测LVI具有挑战性，关于其与临床病理特征的关联数据存在分歧，且此前尚无研究调查观察者间（IrOA）和观察者内（IaOA）的一致性。在此，我们对92例CM患者进行了H&E染色和CD34/SOX10双重染色（DS）以检测LVI，评估IrOA、IaOA以及与其他临床病理特征的关联。
五位作者独立评估了92例连续纳入的回顾性CM病例。我们用H&E染色和CD34/SOX10染色评估IrOA（Fleiss卡方/FK和组内相关系数/ICC）和IaOA（Cohen卡方/CK）。此外，我们比较了两种染色对LVI的评估，并分析了与其他临床病理特征的关联[二分类和分类数据用χ检验；连续数据用Student t检验（正态分布）和Mann-Whitney U检验（非正态分布）]。
IrOA在H&E染色（FK = 0.446；ICC = 0.805）和CD34/SOX10染色（FK = 0.454；ICC = 0.810）时几乎相同；相比之下，对于一位病理学家，H&E染色的IaOA更高（CK：0.809），而对于另一位病理学家，CD34/SOX10染色的IaOA更高（CK：0.563）。应用先前定义的标准，H&E染色和CD34/SOX10染色分别在10例（9.2%）和11例（10.1%）病例中检测到LVI（p = 1.000）。H&E染色和CD34/SOX10染色均与垂直生长期显著相关（H&E染色，p：0.014；CD34/SOX10染色，p：0.010）、有丝分裂≥1/mm²（H&E染色，p：0.000；CD34/SOX10染色，p：0.004）、pT分期（H&E染色，p：0.000；CD34/SOX10染色，p：0.001）、Breslow厚度（H&E染色，p：0.000；CD34/SOX10染色，p：0.001）以及淋巴结和/或远处转移（H&E染色，p：0.005；CD34/SOX10染色，p：0.000）；只有H&E染色与溃疡（p：0.002）和远处转移（p：0.000）相关，相反，只有CD34/SOX10染色与淋巴结转移（p：0.003）相关。
CD34/SOX10染色并不能改善CM中LVI评估的IrOA和IaOA；此外，H&E染色和CD34/SOX10染色与CM其他不良临床病理特征的关联情况相似。因此，在常规诊断情况下，若用于非选择性CM的预后特征分析，CD34/SOX10染色可能是一种多余的诊断工具。
