肝硬化小肝细胞结节与发育不良结节和肝细胞癌（HCC）的鉴别诊断在活检中仍然具有挑战性。由于 TERT 启动子 (pTERT) 突变可能表明结节已经参与恶性过程，本研究的目的是通过 ddPCR 在小型福尔马林固定石蜡包埋 (FFPE) 肝细胞中检测这些突变，以确定与 pTERT 突变相关的组织学标准。我们建立了一个双中心队列数据集，其中包含来自肝硬化样本的 339 个< 2 cm 肝细胞结节，分为包含 299 个切除样本的测试队列和包含 40 个活检样本的验证队列。病理学检查，根据14项组织学标准的评估，对所有结节进行分类。通过 ddPCR 在 FFPE 样品中鉴定出 pTERT 突变。在 339 个结节中，ddPCR 显示 105 例 (31%) 存在 pTERT 突变，其中测试组和验证组分别有 90 例和 15 例。在多变量分析中，三个组织学标准与测试队列中的 pTERT 突变相关：细胞密度增加（P = 0.003）、间质侵袭（P = 0.036）和板增厚异常（P < 0.001）。结合至少两个主要标准，测试队列中预测 pTERT 突变的 AUC 为 0.84（敏感性：86%，特异性：83%），验证队列中预测 pTERT 突变的 AUC 为 0.81（敏感性：87%，特异性：76） %)。我们确定了三个组织学标准作为 pTERT 突变的替代标记，可用于常规活检，以更清楚地对肝硬化中出现的小肝细胞结节进行分类。© 2023 作者。组织病理学由约翰·威利出版

The differential diagnosis of small hepatocellular nodules in cirrhosis between dysplastic nodules and hepatocellular carcinoma (HCC) remains challenging on biopsy. As TERT promoter (pTERT) mutations may indicate the nodules already engaged in the malignant process, the aim of this study was to identify histological criteria associated with pTERT mutations by detecting these mutations by ddPCR in small formalin-fixed paraffin-embedded (FFPE) hepatocellular nodules arising in cirrhosis.We built a bicentric cohort data set of 339 hepatocellular nodules < 2 cm from cirrhotic samples, divided into a test cohort of 299 resected samples and a validation cohort of 40 biopsies. Pathological review, based on the evaluation of 14 histological criteria, classified all nodules. pTERT mutations were identified by ddPCR in FFPE samples. Among the 339 nodules, ddPCR revealed pTERT mutations in 105 cases (31%), including 90 and 15 cases in the test and validation cohorts, respectively. On multivariate analysis, three histological criteria were associated with pTERT mutations in the test cohort: increased cell density (P = 0.003), stromal invasion (P = 0.036) and plate-thickening anomalies (P < 0.001). With the combination of at least two of these major criteria, the AUC for predicting pTERT mutations was 0.84 in the test cohort (sensitivity: 86%, specificity: 83%) and 0.81 in the validation cohort (sensitivity: 87%, specificity: 76%).We identified three histological criteria as surrogate markers of pTERT mutations that may be used in routine biopsy to more clearly classify small hepatocellular nodules arising in cirrhosis.© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.