Pathology Unit, Pancreas Translational and Clinical Research Center, San Raffaele Research Hospital, 20132, Milan, Italy.
Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Research Hospital, Milan, Italy.
Virchows Arch. 2023 Aug;483(2):225-235. doi: 10.1007/s00428-023-03574-x. Epub 2023 Jun 8.
Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of disease. PNI is currently considered as a "present vs. absent" feature, and a severity score system has not yet been established. The aim of the present study was thus to develop and validate a score system for PNI and to correlate it with other prognostic features. In this monocentric retrospective study, 356 consecutive PDAC patients (61.8% upfront surgery patients, 38.2% received neoadjuvant therapy) were analyzed. PNI was scored as follows: 0: absent; 1: the presence of neoplasia along nerves < 3 mm in caliber; and 2: neoplastic infiltration of nerve fibers ≥ 3 mm and/or massive perineural infiltration and/or the presence of necrosis of the infiltrated nerve bundle. For every PNI grade, the correlation with other pathological features, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed. Uni- and multivariate analysis for DFS and DSS were also performed. PNI was found in 72.5% of the patients. Relevant trends between PNI score and tumor differentiation grade, lymph node metastases, vascular invasion, and surgical margins status were found. The latter was the only parameter statistically correlated with the proposed score. The agreement between pathologists was substantial (Cohen's K 0.61). PNI severity score significantly correlated also with decreased DFS and DSS at univariate analysis (p < 0.001). At multivariate analysis, only the presence of lymph node metastases was an independent predictor of DFS (HR 2.235 p < 0.001). Lymph node metastases (HR 2.902, p < 0.001) and tumor differentiation grade (HR 1.677, p = 0.002) were independent predictors of DSS. Our newly developed PNI score correlates with other features of PDAC aggressiveness and proved to have a prognostic role though less robust than lymph nodes metastases and tumor differentiation grade. A prospective validation is needed.
神经周围侵犯（PNI）是胰腺导管腺癌（PDAC）的常见特征，并且与疾病早期的侵袭性肿瘤行为相关。PNI 目前被认为是一个“存在或不存在”的特征，尚未建立严重程度评分系统。因此，本研究旨在开发和验证 PNI 评分系统，并将其与其他预后特征相关联。在这项单中心回顾性研究中，分析了 356 例连续 PDAC 患者（61.8%为初始手术患者，38.2%接受新辅助治疗）。PNI 评分如下：0：不存在；1：肿瘤沿神经存在，神经直径 < 3 毫米；2：神经纤维肿瘤浸润 ≥ 3 毫米和/或大量神经周围浸润和/或浸润神经束坏死。对于每个 PNI 分级，分析与其他病理特征、无病生存期（DFS）和疾病特异性生存期（DSS）的相关性。还对 DFS 和 DSS 进行了单变量和多变量分析。在 72.5%的患者中发现了 PNI。发现 PNI 评分与肿瘤分化程度、淋巴结转移、血管侵犯和手术切缘状态之间存在相关趋势。后者是与提出的评分唯一具有统计学相关性的参数。病理学家之间的一致性很高（Cohen's K 0.61）。在单变量分析中，PNI 严重程度评分与降低的 DFS 和 DSS 显著相关（p < 0.001）。在多变量分析中，只有淋巴结转移的存在是 DFS 的独立预测因素（HR 2.235 p < 0.001）。淋巴结转移（HR 2.902，p < 0.001）和肿瘤分化程度（HR 1.677，p = 0.002）是 DSS 的独立预测因素。我们新开发的 PNI 评分与 PDAC 侵袭性的其他特征相关，并且通过证明比淋巴结转移和肿瘤分化程度具有较弱的预后作用而具有预后作用。需要前瞻性验证。
