Angerilli Valentina, Vink-Börger M Elisa, van Roermund Nanette S, van Lijnschoten Gesina, Kuijpers Chantal C H J, van Grieken Nicole C T, Fassan Matteo, Ijspeert Joep E, van der Post Rachel S, Nagtegaal Iris D
Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Surgical Pathology Unit, ULSS2 Marca Trevigiana, Treviso, Italy.
Histopathology. 2026 Mar 14. doi: 10.1111/his.70135.
Sessile serrated lesions with dysplasia (SSLd) are direct precursors of colorectal carcinomas (CRCs) but pose a diagnostic challenge. We aim to explore contemporary practice leading to recommendations to improve detection of dysplasia.
(i) The frequency of dysplasia in SSLs was estimated through a nationwide study of individuals undergoing colonoscopy in the Netherlands (2014-2022). Out of 186 427 SSLs, 17 456 showed dysplasia, yielding a frequency of 9.4%. (ii) A national audit evaluating diagnostic practices and interobserver variability revealed diagnostic discrepancies in 11% of SSLd cases, while ancillary immunohistochemistry (IHC) was used by only 20% of participating laboratories. (iii) The additional value of biomarkers (MLH1, p16, p53, beta-catenin and c-myc) was assessed using retrospective (n = 213) and prospective (n = 348) SSL cohorts. MLH1 emerged as the only useful biomarker for identifying dysplasia among SSLs, increasing SSLd diagnoses from 33 to 41 cases in the retrospective cohort (P = 0.008) and from 35 to 43 cases in the prospective cohort (P = 0.013). (iv) Misdiagnosis of SSLd among conventional adenomas was investigated using BRAF IHC in a cohort of 1572 advanced adenomas and was found to be very rare, occurring in only 2 cases.
The diagnosis of SSLd appears to have good reproducibility among pathologists and positive diagnostic trends that are observed in recent years. MLH1 is the only IHC marker with robust clinical utility to identify SSLd that do not meet the morphologic criteria for overt dysplasia but should be used only in selected cases due to its low prevalence.
伴发育异常的无蒂锯齿状病变（SSLd）是结直肠癌（CRC）的直接前驱病变，但在诊断上具有挑战性。我们旨在探索当代实践，以提出改善发育异常检测的建议。
（i）通过对荷兰（2014 - 2022年）接受结肠镜检查的个体进行全国性研究，估计SSL中发育异常的频率。在186427个SSL中，17456个显示发育异常，频率为9.4%。（ii）一项评估诊断实践和观察者间变异性的全国性审计显示，11%的SSLd病例存在诊断差异，而仅20%的参与实验室使用辅助免疫组织化学（IHC）。（iii）使用回顾性（n = 213）和前瞻性（n = 348）SSL队列评估生物标志物（MLH1、p16、p53、β-连环蛋白和c-myc）的附加价值。MLH1成为唯一用于识别SSL中发育异常的有用生物标志物，在回顾性队列中，SSLd诊断从33例增加到41例（P = 0.008），在前瞻性队列中从35例增加到43例（P = 0.013）。（iv）在1572例高级别腺瘤队列中，使用BRAF IHC研究常规腺瘤中SSLd的误诊情况，发现非常罕见，仅发生2例。
SSLd的诊断在病理学家中似乎具有良好的可重复性，并且近年来观察到有积极的诊断趋势。MLH1是唯一具有强大临床效用的IHC标志物，可用于识别不符合明显发育异常形态学标准的SSLd，但由于其低患病率，应仅在特定病例中使用。
