OBJECTIVE To evaluate the morphologic landscape of pancreatic ductal adenocarcinoma (PDAC), intratumor spatial heterogeneity, and the resulting clinical impact following post-neoadjuvant pancreatectomy. SUMMARY BACKGROUND DATA The clinical value of PDAC morphologic subtypes and intratumor spatial heterogeneity post-treatment remains an open issue. MATERIALS AND METHODS The study cohort included patients who underwent post-neoadjuvant pancreatectomy for PDAC at the University of Verona Hospital Trust between 2013 and 2019. All hematoxylin and eosin-stained slides were reviewed to assess PDAC histomorphology and intratumor heterogeneity. The relationship with other clinicopathological variables, overall survival (OS), and recurrence-free (RFS) survival was evaluated using standard statistics. RESULTS The study cohort included 400 patients. Histological revision identified ten different morphologic subtypes. Gland-forming PDAC with a conventional pattern was the most frequently identified subtype (41.8%). Overall, 247 tumors (61.7%) showed only one histological pattern and were classified as homogeneous, whereas 153 (38.3%) showed different morphologies and were classified as heterogeneous tumors. The median post-resection survival was 30.1 months (95%CI 26.6-33.5). There was a substantial survival variability according to the morphologic subtype, ranging from 19.1 months in the gyriform subtype to 47.0 months in the papillary subtype. Tumors with a heterogeneous morphology displayed a higher rate of nodal metastases, worse tumor regression metrics, and worse oncologic outcomes relative to spatially homogeneous tumors. DISCUSSION This paper provided a morphological taxonomy of residual tumors following post-neoadjuvant pancreatectomy for PDAC. The morphologic subtype and intratumor spatial heterogeneity have relevant prognostic implications and could be included in the pathology report to complement regression metrics.

中文翻译：

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新辅助胰腺切除术后胰腺导管腺癌的形态学特征和肿瘤内异质性的临床价值。


目的 评价胰腺导管腺癌 （PDAC） 的形态学景观、肿瘤内空间异质性以及新辅助胰腺切除术后由此产生的临床影响。总结 背景数据 PDAC 形态学亚型和治疗后肿瘤内空间异质性的临床价值仍然是一个悬而未决的问题。材料和方法 研究队列包括 2013 年至 2019 年期间在维罗纳大学医院信托基金接受新辅助胰腺切除术后 PDAC 的患者。回顾所有苏木精和伊红染色载玻片，以评估 PDAC 组织形态学和肿瘤内异质性。使用标准统计评估与其他临床病理变量、总生存期 （OS） 和无复发 （RFS） 生存期的关系。结果 研究队列包括 400 名患者。组织学修订确定了 10 种不同的形态学亚型。具有常规模式的腺体形成 PDAC 是最常见的亚型 （41.8%）。总体而言，247 例肿瘤 （61.7%） 仅显示一种组织学模式，并被归类为同质性，而 153 例 （38.3%） 表现出不同的形态，被归类为异质性肿瘤。中位术后生存时间为 30.1 个月 （95% CI 26.6-33.5）。根据形态学亚型，生存率存在很大差异，从回状亚型的 19.1 个月到状亚型的 47.0 个月不等。相对于空间同质性肿瘤，具有异质性形态的肿瘤显示出更高的淋巴结转移率、更差的肿瘤消退指标和更差的肿瘤学结果。讨论 本文提供了 PDAC 新辅助胰腺切除术后残留肿瘤的形态学分类学。 形态学亚型和肿瘤内空间异质性具有相关的预后意义，可以包含在病理报告中以补充回归指标。