Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

Sep 24, 2026

Sessile serrated lesions with dysplasia (SSLDs) are an intermediate stage in the serrated neoplasia pathway that connects sessile serrated lesions to invasive colorectal cancer (CRC). SSLDs are linked to faster progression to immunogenic MSI-H CRC or mesenchymal MSS CRC, yet their flat morphology and brief intermediate window hinder detection, enabling post-colonoscopy or interval cancers. Review evidence addresses terminology issues, summarizes longitudinal gaps, and integrates clinical, histological, single-cell molecular, and tumor microenvironment findings. Recent colonoscopy advances and experimental models are used to clarify clinical implications and biological mechanisms.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Classification of serrated polyps

J Gastroenterol (2023) 58:705–717 [https://doi.org/10.1007/s00535-023-02003-9](https://doi.org/10.1007/s00535-023-02003-9) REVIEW Sessile serrated lesions with dysplasia: is it possible to nip them in the bud? Takahiro Utsumi1 • Yosuke Yamada2 • Maria Teresa Diaz-Meco3 • Jorge Moscat3 • Yuki Nakanishi1 Received: 23 March 2023 / Accepted: 14 May 2023 / Published online: 23 May 2023 􀀂 The Author(s) 2023 Abstract The serrated neoplasia pathway constitutes an‘‘alternative route’’ to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic ([ 10–15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their ﬂat shapes and the relatively short window of this intermediate state make it difﬁcult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identiﬁed distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME) . Molecular studies at the single-cell level have identiﬁed distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in & Yuki Nakanishi [yuki@kuhp.kyoto-u.ac.jp](yuki@kuhp.kyoto-u.ac.jp) 1 Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan 2 Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan 3 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignantSSLs. Recent progress in all aspects of the ﬁeld has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications. Keywords Serrated pathway 􀀂 SSL 􀀂 SSLD 􀀂 Classiﬁcation 􀀂 Tumor microenvironment Introduction Colorectal cancer (CRC) is the third most common malignancy worldwide and the second leading cause of cancer-related death [1] . Colonoscopy is used to detect and simultaneously remove pre-malignant colorectal polyps before they develop into invasive cancers. However, several studies have reported that 5–8% of all CRCs are diagnosed in patients who have undergone colonoscopies 3–5 years before diagnosis [2–6] . These cancers are usually called post-colonoscopy CRCs or interval CRCs, and have become an important clinical issue that attracts physicians’ attention. Three decades ago, sporadic CRCs were considered to arise exclusively from colorectal adenomas through the‘‘adenoma–carcinoma sequence,’’ and colorectal serrated polyps, characterized by a saw-toothed pattern of colonic crypts, were thought to be harmless hyperplastic lesions [7, 8] . However, serrated polyps have now been recognized as alternative precursors that potentially progress to CRC, representing another key oncogenic route, named ‘‘serrated neoplasia pathway,’’ which accounts for approximately 15–30% of sporadic CRCs [9–13] . In this alternative route, CRCs mostly arise from sessile serrated lesions (SSLs), which display a ﬂat elevated hyperplastic mucosa with a unique morphological change in crypt bottom, such as a‘‘boot’’ or ‘‘inverted T’’ shape appearance. After gradual growth for a long period (typically over 10–

FAQs

What role do sessile serrated lesions with dysplasia (SSLDs) play in the serrated neoplasia pathway?

SSLDs are an intermediate step between sessile serrated lesions (SSLs) and invasive colorectal cancer (CRC) in the alternative serrated pathway.

Why are SSLDs difficult to detect during colonoscopy?

Their flat morphology and a relatively short intermediate state make them challenging to detect and diagnose, which can contribute to post-colonoscopy or interval cancers.

What is the aim of the review article?

To assess current knowledge of SSLDs and highlight their clinical implications, including molecular and tumor microenvironment aspects.

Sep 24, 2026

Uploaded by Aria Callaghan