Review Article From Mixed Hyperplastic/Adenomatous Polyp to Sessile Serrated Lesion A Long and Winding Road for Long and Winding Crypts Adam L. Booth, MD; Melissa W. Taggart, MD; Yuho Ono, MD; Raul S. Gonzalez, MD  Context.—During the past 3 decades, numerous articles in the literature have offered terminology, diagnostic criteria, and consensus recommendations regarding the entity currently referred to by the World Health Organi- zation as sessile serrated lesion. Given the many names and various, variably reproducible diagnostic criteria ascribed to sessile serrated lesion, confusion persists for many pathologists and gastroenterologists regarding the diagno- sis. This distinction is important, as sessile serrated lesion can progress to malignancy, unlike its main differential diagnosis, hyperplastic polyp. Research studies have shed light on the characteristic architecture and morphology, immunohistochemical patterns, and molecular alterations of sessile serrated lesion, and multiple consensus meetings around the globe have developed their criteria and nomenclature, often clashing or mixing terms. Objective.—To provide a narrative review from the entity’s early description to our current understanding. Data Sources.—The existing scientific and clinical literature, published texts, medical society recommenda- tions, and specialty consensus guidelines. Conclusions.—The current World Health Organization criteria are a distillation of this scientific process, but terminology is still a point of contention worldwide. (Arch Pathol Lab Med. 2021;145:1289–1296; doi: 10.5858/arpa.2020-0591-RA) S essile serrated lesion (SSL) is the current World Health Organization (WHO)–recommended terminology 1 for a type of serrated colorectal polyp characterized by disordered maturation, abnormal basal crypt growth, and propensity for developing cytologic dysplasia and ultimately carcinoma. The WHO diagnostic criteria indicate that a polyp with at least one unequivocal architecturally distorted serrated crypt ‘‘defined as horizontal growth above the muscularis mucosae, dilation of the crypt base, serrations extending into the crypt base, and asymmetrical proliferation’’ be interpreted as an SSL. They note that these lesions often are proximally located, but that location and size should be considered only when orientation or ambiguity complicates the diagnosis. 1 Both the nomenclature and the diagnostic criteria for SSL have changed multiple times since the entity’s first description, often leading to confusion and consternation on the part of pathologists and gastroenter- ologists. This nomenclatural vacillation is illustrated in Figure 1, which plots the use of the most common terms in the literature over time and may serve as a guide for the reader. 2 Before the 1980s, 2 types of colon polyps were recognized: the hyperplastic polyp (HP; Figure 2, A) and the traditional or conventional adenoma (TA). 3 Hyperplastic polyps were frequently small (,0.5 cm) and sessile, with serrated architecture and mature goblet cells lacking dysplasia. 4 Traditional adenomas varied from tubular to villous in architecture, with crowded glands composed of pseudo- stratified dysplastic columnar cells and immature goblet cells. Most importantly, HPs were uniformly considered benign, whereas TAs were recognized as preneoplastic lesions in the adenoma-carcinoma sequence, which itself was hotly debated until at least the mid-1970s. 5–11 With considerable advances in subsequent decades, a broad array of preneoplastic polyps has been recognized. This includes SSLs (Figure 2, B), which were undoubtedly misinterpreted as HPs by pathologists for decades. Similarly, sessile lesions were often missed by endoscopists because of their subtle, flat gross appearance or not biopsied because endoscopic features can overlap with those of benign HPs. 12 As published literature grew, so did detection by endosco- pists and diagnosis by pathologists. 12–16 Although TAs can progress to colorectal carcinoma (CRC) via the chromosomal instability pathway, SSLs serve as precursor lesions for most of the approximately 30% of CRC that arises through the serrated neoplasia pathway. 17,18 That pathway is thought to begin with activating mutations in Accepted for publication October 15, 2020. Published online December 22, 2020. Supplemental digital content is available for this article at https:// meridian.allenpress.com/aplm in the October 2021 table of con- tents. From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez); and the Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston (Taggart). The authors have no relevant financial interest in the products or companies described in this article. Corresponding author: Raul S. Gonzalez, MD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (email: rgonzal5@bidmc.harvard.edu). Arch Pathol Lab Med—Vol 145, October 2021 Nomenclature Timeline for Sessile Serrated Lesion—Booth et al 1289