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Batts KP, Cinnor B, Kim A, Stickney E, Burgart LJ. Sessile Serrated Adenoma With Dysplasia of the Colon. Am J Clin Pathol 2022; 157:180-195. [PMID: 34542560 DOI: 10.1093/ajcp/aqab112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/01/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Sessile serrated adenomas with dysplasia (SSADs) of the colon are transitional lesions between sessile serrated adenomas (SSAs) and a subset of colorectal adenocarcinomas. We wished to gain insight into the relative percentages and significance of SSAD subtypes. METHODS Retrospective (2007-2012) clinicopathologic review of colorectal polyps initially regarded as having mixed serrated and dysplastic elements. SSADs were subdivided into those with cap-like adenomatous dysplasia (ad1), non-cap-like adenomatous dysplasia (ad2), serrated dysplasia (ser), minimal dysplasia (min), and dysplasia not otherwise specified (nos). MLH1 immunostaining was performed on many. RESULTS SSADser (7.7%) had a greater propensity for right colon, women, and MLH1 loss vs the entire cohort. SSAad1 (11.6%) had the least female preponderance, was least likely to have MLH1 loss, and was most likely to affect the left colorectum. SSAD with MLH1 loss was associated with an increased burden of SSAs in the background colon (P = .0003) but not tubular adenomas or hyperplastic polyps. Most SSADs (ad2 and nos groups, 80% combined) showed difficult-to-classify dysplasia, intermediate MLH1 loss rates, and intermediate clinical features. CONCLUSIONS While some trends exist, morphologically subclassifying SSADs is probably not justified in routine clinical practice. MLH1 loss portends a greater burden of SSAs in the background colon.
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Affiliation(s)
| | | | - Adam Kim
- MNGI Digestive Health, Minneapolis, MN, USA
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2
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Booth AL, Taggart MW, Ono Y, Gonzalez RS. From Mixed Hyperplastic/Adenomatous Polyp to Sessile Serrated Lesion: A Long and Winding Road for Long and Winding Crypts. Arch Pathol Lab Med 2020; 145:1289-1296. [PMID: 33351878 DOI: 10.5858/arpa.2020-0591-ra] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 11/06/2022]
Abstract
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 Organization 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 diagnosis. 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 recommendations, 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.
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Affiliation(s)
- Adam L Booth
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Melissa W Taggart
- The Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston (Taggart)
| | - Yuho Ono
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Raul S Gonzalez
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
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3
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Batts KP, Atwaibi M, Weinberg DI, McCabe RP. Significance of serrated epithelial change in inflammatory bowel disease. Postgrad Med 2020; 133:66-70. [PMID: 32746680 DOI: 10.1080/00325481.2020.1802138] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The clinical significance of hyperplastic polyp-like histologic changes in random biopsy samples ('serrated epithelial change' or SEC) from patients with inflammatory bowel disease (IBD) remains uncertain, with some studies suggesting an increased risk of dysplasia and even carcinoma. Controlled studies are few. We studied the significance of SEC on the development of dysplasia in follow-up surveillance of IBD patients in our system. METHODS We identified 94 IBD patients with SEC and 187 IBD patients without SEC identified in index biopsy samples, and retrospectively collated results of follow-up surveillance samples in each group, with the development of dysplasia and/or adenocarcinoma as study endpoints. RESULTS IBD patients with SEC had a 12.8% likelihood of developing dysplasia of any type within IBD-affected areas vs a 4.3% likelihood in non-SEC patients (follow-up in the 1-4 year range for each group). This was significant in univariate analysis (p = 0.013) but not in multivariate analysis, likely due to increased frequency of follow-up sampling in the SEC patients. One cancer developed in each group (p = NS). CONCLUSION Our data, in the context of other studies, neither prove nor conclusively exclude an increased risk of dysplasia in IBD patients with SEC. But cancer risk appears low and continued surveillance at usual intervals seems reasonable.
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Affiliation(s)
- Kenneth P Batts
- Department of Pathology and Lab Medicine, Hospital Pathology Associates, PC , Minneapolis, MN, USA.,Virginia Piper Cancer Institute , Minneapolis, MN, USA
| | | | - David I Weinberg
- Virginia Piper Cancer Institute , Minneapolis, MN, USA.,Department of Gastroenterology, MNGI Digestive Health , Minneapolis, MN, USA
| | - Robert P McCabe
- Virginia Piper Cancer Institute , Minneapolis, MN, USA.,Department of Gastroenterology, MNGI Digestive Health , Minneapolis, MN, USA
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Nouraie M, Ashktorab H, Atefi N, Azam S, Tarjoman T, Lee E, Shokrani B, Afsari A, Soleimani A, Laiyemo AO, Singh S, Brim H. Can the rate and location of sessile serrated polyps be part of colorectal Cancer disparity in African Americans? BMC Gastroenterol 2019; 19:77. [PMID: 31126232 PMCID: PMC6534887 DOI: 10.1186/s12876-019-0996-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 05/16/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Up to 30% of colorectal cancers develop through the serrated pathway. African Americans (AAs) suffer a disproportionate burden of colorectal cancer. The aim of this study was to evaluate clinicopathological features of AA patients diagnosed with sessile serrated polyps (SSPs). METHODS We conducted a retrospective study of all colonoscopies (n = 12,085) performed at Howard University Hospital, from January 1st, 2010 to December 31st, 2015, of which 83% were in AA patients, (n = 10,027). Among AAs, pathology reports confirmed 4070 patients with polyps including 252 with SSPs. Demographic and clinical variables (i.e. sex, age, BMI, anatomic location, clinical symptoms, polyp size, and clinical indications were collected at colonoscopy. RESULTS In the AA population, the median age was 56 with interquartile range (IQR) of 51 to 62 years, 54% were female, and 48% had a BMI > 30. The most common reason for colonoscopy was screening (53%), whereas the prevalent reasons for diagnostic colonoscopies were changes in bowel habits (18%) and gastrointestinal bleeding (17%). The total number of SSPs among the 252 AA (diagnosed with SSPs) was 338. Of these, 9% (n = 29/338) had some degree of cytological dysplasia, primarily in the ascending colon (n = 6/42, 14%), Transverse colon (n = 2/16, 13%) and rectosigmoid (n = 19/233, 8%). About 24% of patients had more than 2 polyps. Most patients (76%) had distal SSPs (rectal and rectosigmoid), in comparison to 14% of proximal polyps and 10% of bilateral locations. Median SSA/P size for all locations was 0.6 cm. CONCLUSION The prevalence of SSPs accounts for 6% of all polyps in AA patients and was diagnosed in 2.5% of all colonoscopies (n = 252/10,027), which is higher than Caucasians in the US. SSPs were predominantly located in the left side, as compared to published literature showing the predominance in the right side of the colon. Screening of CRC will have the chance to detect high risk SSA/P in this population.
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Affiliation(s)
- Mehdi Nouraie
- University of Pittsburg, Medical center, Pittsburg, PA, USA.
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, USA.
| | - Hassan Ashktorab
- Department of Medicine, College of Medicine, Washington, DC, USA.
- Cancer Research Center and Department of Medicine, Howard University College of Medicine, 2041 Georgia Avenue, Washington, D.C, N.W., 20060, USA.
| | - Nazli Atefi
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Saman Azam
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Taraneh Tarjoman
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Edward Lee
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Babak Shokrani
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Ali Afsari
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Akbar Soleimani
- Department of Medicine, College of Medicine, Washington, DC, USA
| | | | - Sanmeet Singh
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Hassan Brim
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
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5
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Cassese G, Amendola A, Maione F, Giglio MC, Pagano G, Milone M, Aprea G, Luglio G, De Palma GD. Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management. Gastroenterol Res Pract 2019; 2019:9179718. [PMID: 30774654 PMCID: PMC6350577 DOI: 10.1155/2019/9179718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023] Open
Abstract
Prompt diagnosis and correct management of the so called "serrated lesions" (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
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Affiliation(s)
- Gianluca Cassese
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Alfonso Amendola
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Francesco Maione
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Mariano Cesare Giglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gianluca Pagano
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Marco Milone
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Aprea
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gaetano Luglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Domenico De Palma
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
- Center of Excellence for Technological Innovation in Surgery, University of Naples “Federico II”, Italy
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6
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Pyo JH, Ha SY, Hong SN, Chang DK, Son HJ, Kim KM, Kim H, Kim K, Kim JE, Choi YH, Kim YH. Identification of risk factors for sessile and traditional serrated adenomas of the colon by using big data analysis. J Gastroenterol Hepatol 2018; 33:1039-1046. [PMID: 29087626 DOI: 10.1111/jgh.14035] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/23/2017] [Accepted: 10/24/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Little is known about the risk factors associated with serrated polyps, because the early studies, which occurred before the new World Health Organization classification was introduced, included mixtures of serrated polyps. This study aimed to evaluate the risk factors associated with the presence of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) using big data analytics. METHODS Using a case-control design, we evaluated the risk factors associated with the presence of SSAs and TSAs. Subjects who underwent colonoscopies from 2002 to 2012 as part of the comprehensive health screening programs undertaken at the Samsung Medical Center, Korea, participated in this study. RESULTS Of the 48 677 individuals who underwent colonoscopies, 183 (0.4%) had SSAs and 212 (0.4%) had TSAs. The multivariate analysis determined that being aged ≥ 50 years (odds ratio [OR] 1.91, 95% confidential interval [CI] 1.27-2.90, P = 0.002) and a history of colorectal cancer among first-degree relatives (OR 3.14, 95% CI 1.57-6.27, P = 0.001) were significant risk factors associated with the presence of SSAs and that being aged ≥ 50 years (OR 2.61, 95% CI 1.79-3.80, P < 0.001), obesity (OR 1.63, 95% CI 1.12-2.36, P = 0.010), and a higher triglyceride level (OR 1.63, 95% CI 1.12-2.36, P = 0.010) were independent risk factors associated with the presence of TSAs. CONCLUSIONS We used big data analytics to determine the risk factors associated with the presence of specific polyp subgroups, and individuals who have these risk factors should be carefully scrutinized for the presence of SSAs or TSAs during screening colonoscopies.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Jung Son
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea.,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyeseung Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Jee Eun Kim
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea.,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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7
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De Maio G, Zama E, Rengucci C, Calistri D. What influences preneoplastic colorectal lesion recurrence? Oncotarget 2017; 8:12406-12416. [PMID: 27902488 PMCID: PMC5355354 DOI: 10.18632/oncotarget.13628] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 11/15/2016] [Indexed: 12/16/2022] Open
Abstract
The hypothesis of the local recurrence of preneoplastic lesions was first put forward in the 1950s. Disease recurrence may result from an inherent imbalance in cell proliferation that promotes carcinogenesis in apparently normal mucosa. Our review sheds light on how early preneoplastic lesions could be used to diagnose relapsed preneoplastic and, developing neoplastic lesions. We focus in detail on the clinical-pathological and molecular features of adenoma subtypes and their role in relapsed adenoma and their development into colorectal carcinoma. Moreover, we include the data available on microbiota and its metabolites and their role in recurrence. We strongly believe that a significant improvement could be achieved in colorectal screening by introducing personalized endoscopic surveillance for polyp-bearing patients on the basis of the presence of molecular markers that are predictive of recurrence.
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Affiliation(s)
- Giulia De Maio
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
| | - Elisa Zama
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
| | - Claudia Rengucci
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
| | - Daniele Calistri
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
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8
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Prevalence and Anatomic Distribution of Serrated and Adenomatous Lesions in Patients with Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2017; 2017:5490803. [PMID: 28182112 PMCID: PMC5274674 DOI: 10.1155/2017/5490803] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 06/01/2016] [Accepted: 08/18/2016] [Indexed: 12/29/2022] Open
Abstract
Background. Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) have not been well characterized in patients with inflammatory bowel disease (IBD). This study assesses the prevalence and anatomic distribution of SSA/Ps, TSAs, and conventional adenomas/dysplasia (Ad/Ds) in IBD patients. Methods. IBD patients with serrated, adenomatous, or hyperplastic lesions between 2005 and 2009 were identified in the regional tertiary-care hospital database. Clinicopathological information was reviewed and the histology of biopsies was reevaluated. Results. Ninety-six Ad/Ds, 25 SSA/Ps, and 4 TSAs were identified in 83 patients. Compared to Ad/Ds, serrated lesions were more prevalent in females (p = 0.046). The prevalence of Ad/Ds was 4.95%, SSA/Ps was 1.39%, and TSAs was 0.31%. No relationship was identified between lesion type and IBD type. Comparing all IBD patients, the distribution of lesion types was significantly different (p = 0.02) with Ad/Ds more common distally, SSA/Ps more common proximally, and TSAs evenly distributed. Among Crohn's disease (CD) patients, a similar distribution difference was noted (p < 0.001). However, ulcerative colitis (UC) patients had a uniform distribution of lesion types (p = 0.320). Conclusions. IBD patients have a lower prevalence of premalignant lesions compared to the general population, and the anatomic distribution of lesions differed between CD and UC patients. These findings may indicate an interaction between lesion and IBD pathogenesis with potential clinical implications.
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9
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Mikhaleva LM, Komleva RA, Biryukov AE, Shakhpazyan NK. [Serrated adenomas of the colon: Clinical, morphological, and molecular genetic characteristics]. Arkh Patol 2017; 79:19-27. [PMID: 28295004 DOI: 10.17116/patol201779119-27] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
AIM to investigate the clinical, morphological, and molecular genetic characteristics of serrated adenomas of the colon. MATERIAL AND METHODS The study included 82 colon adenomas from 63 patients aged 29 to 81 years, who underwent colonoscopy with biopsy or polypectomy. The mean age of men was 63.3 years; that of women was 56.8 years. Comprehensive clinical, morphological, immunohistochemical, and molecular genetic examinations were made. RESULTS The histological examination showed that sessile serrated adenomas (SSA) of the colon were most common (46.4%), while hyperplastic polyp (HP) and traditional serrated adenoma (TSA) were found less often and with the same frequency (26.8%). The most typical location of SSA was the right colon; that of TSA was the left one. HP was detected equally on both sides of the colon. The immunohistochemical examination of the subtypes revealed no significant differences in the expression of markers. An analytical panel of antibodies against Desmin, Podoplanin (D2-40), CK20, CD34, Ki-67, Muc2, CEA, and CDX2 was used when identifying dysplasia areas, suspecting malignancy with invasion into the muscular layer of the mucous membrane and when determining the possible presence of emboli in blood and lymph vessels. BRAF gene mutation was identified in half of SSA cases; genetic BRAF mutation was observed in 41.7% of HP cases; genetic KRAS mutation was seen in 16.6%. The patients with TSA showed KRAS and BRAF mutations in 58.4 and 8.3% of cases, respectively. Mutations of these genes were absent. CONCLUSION The study revealed that the subtypes of serrated adenomas substantially differ by sex, age, localization, and molecular genetic characteristics.
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Affiliation(s)
- L M Mikhaleva
- Research Institute of Human Morphology, Moscow, Russia; City Clinical Hospital Thirty-One, Moscow Healthcare Department, Moscow, Russia
| | - R A Komleva
- Research Institute of Human Morphology, Moscow, Russia
| | - A E Biryukov
- Research Institute of Human Morphology, Moscow, Russia; City Clinical Hospital Thirty-One, Moscow Healthcare Department, Moscow, Russia
| | - N K Shakhpazyan
- City Clinical Hospital Thirty-One, Moscow Healthcare Department, Moscow, Russia
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10
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Medlicott SAC, Urbanski SJ. Acquired Diverticulosis of the Vermiform Appendix: A Disease of Multiple Etiologies. Int J Surg Pathol 2016. [DOI: 10.1177/106689699800600106] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Acquired diverticular disease of the vermiform appendix is a rare condition that usually presents with the symptoms of acute appendicitis. This analysis was undertaken to determine the spectrum and prevalence of the associated lesions in acquired appendiceal diverticulosis. Thirty-one cases of acquired appendiceal diverticular disease were identified from files over a period of 15 years (1982-1996). Diverticulosis was the only abnormality in 17 cases (54.8%). An associated neoplastic epithelium was present in nine (29%) patients (seven adenomata and two goblet cell carcinoids), fecalith formation in three (9.7%), and a neuroma in two (6.5%). Although rare, diverticular disease of the vermiform appendix was frequently seen in association with an adenomatous mucosa. In our experience, one appendiceal adenoma coexisted with a colonic adenocarcinoma. In conclusion, the diagnosis of appendiceal diverticulosis necessitates the exclusion of coexisting appendiceal neoplasia.
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Affiliation(s)
| | - S. J. Urbanski
- Department of Histopathology, Foothills Hospital, Calgary, Alberta
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11
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Yang HM, Mitchell JM, Sepulveda JL, Sepulveda AR. Molecular and histologic considerations in the assessment of serrated polyps. Arch Pathol Lab Med 2015; 139:730-41. [PMID: 26030242 DOI: 10.5858/arpa.2014-0424-ra] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
UNLABELLED CONTEXT : Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp-carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors. OBJECTIVE To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance. DATA SOURCES Published literature focused on serrated polyps and their association with colorectal cancer. CONCLUSIONS Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps.
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Affiliation(s)
- Hui-Min Yang
- From the Department of Pathology and Cell Biology, Columbia University, New York, New York
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12
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Bettington ML, Chetty R. Traditional serrated adenoma: an update. Hum Pathol 2015; 46:933-8. [PMID: 26001333 DOI: 10.1016/j.humpath.2015.04.002] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 03/29/2015] [Accepted: 04/03/2015] [Indexed: 02/06/2023]
Abstract
Although recognized 25 years ago, the traditional serrated adenoma (TSA) remains an ongoing source of diagnostic and biologic debate. Recent research has greatly improved our understanding of the morphological and molecular aspects of these polyps. In particular, the recognition of ectopic crypt foci (ECFs) in combination with typical cytology and slitlike serrations improves diagnostic reproducibility. Awareness that many TSAs, particularly BRAF-mutated TSAs, arise in precursor microvesicular hyperplastic polyps and sessile serrated adenomas can aid in making this diagnosis and should not be confused with a sessile serrated adenoma with dysplasia. At a molecular level, TSAs can be divided into 2 groups based on their BRAF or KRAS mutation status. The development of overt cytologic dysplasia is accompanied by TP53 mutation, Wnt pathway activation, and, in some cases, silencing of CDKN2A. Importantly, however, mismatch repair enzyme function is retained. Thus, the TSA is an important precursor of aggressive molecular subtypes of colorectal carcinoma.
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Affiliation(s)
- Mark L Bettington
- The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, School of Medicine, University of Queensland, Envoi Specialist Pathologists, Brisbane 4072, Queensland, Australia
| | - Runjan Chetty
- Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
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13
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Crockett SD, Snover DC, Ahnen DJ, Baron JA. Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol 2015; 13:11-26.e1. [PMID: 24216467 DOI: 10.1016/j.cgh.2013.10.035] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 10/29/2013] [Accepted: 10/31/2013] [Indexed: 02/07/2023]
Abstract
The concept of serrated colorectal neoplasia and a serrated pathway to colorectal cancer (CRC) is relatively new and continuing to evolve, but it has become highly relevant to gastroenterologists, pathologist, and oncologists alike. Sessile serrated adenomas (SSA) are now thought to be the major precursor lesion of serrated pathway cancers, which represent up to one-third of all sporadic CRC cases. However, despite their increasingly recognized importance, relatively little is known about the epidemiology and natural history of SSAs, and the molecular and epigenetic aspects are incompletely understood. Endoscopists must be aware of the unique features of SSAs so that the practice of colonoscopic screening for CRC can include optimized detection, removal, and appropriate surveillance of SSAs and other serrated precursor lesions. In this review, we discuss the history, epidemiology, and pathologic aspects of SSAs, as well as a recommended management approach and a discussion of uncertainties and opportunities for future research.
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Affiliation(s)
- Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
| | - Dale C Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, Minnesota
| | - Dennis J Ahnen
- Division of Gastroenterology, Department of Veterans Affairs Eastern Colorado Health Care System and University of Colorado School of Medicine, Denver, Colorado
| | - John A Baron
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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Kharlova OA, Danilova NV, Malkov PG, Ageikina NV, Knyazev MV. [Serrated lesions of the large bowel]. Arkh Patol 2015; 77:60-68. [PMID: 25868371 DOI: 10.17116/patol201577160-] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
The 2010 WHO classification identifies a new group of pretumor lesions of the large bowel--serrated masses, which includes hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/P), and traditional serrated adenomas (TSA). Serrated masses are a heterogeneous group characterized by serrated gland lumens and, in most cases, without dysplasia. An enlarged proliferative zone, elongated crypts, and no cytological atypia in addition to a serrated lumen are typical of HPs. SSA/P is characterized by the migration of the proliferative zone to the crypt walls, giving rise to specific architectural disorders, such as expanded and horizontally growing basal gland segments along the lamina muscularis mucosae. TSA is typified by short ectopic crypts that cannot reach the lamina muscularis and by epithelial eosinophilic changes. SSA/P and TSA have peculiar molecular genetic profiles and proven malignant potential.
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Affiliation(s)
- O A Kharlova
- Russian Medical Academy of Postgraduate Education, Moscow
| | - N V Danilova
- Russian Medical Academy of Postgraduate Education, Moscow; Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow
| | - P G Malkov
- Russian Medical Academy of Postgraduate Education, Moscow; Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow
| | - N V Ageikina
- Polyclinic Two, Ministry of Economic Development of Russia, Moscow
| | - M V Knyazev
- Polyclinic Two, Ministry of Economic Development of Russia, Moscow
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Anderson JC. Pathogenesis and management of serrated polyps: current status and future directions. Gut Liver 2014; 8:582-9. [PMID: 25368744 PMCID: PMC4215442 DOI: 10.5009/gnl14248] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 08/20/2014] [Indexed: 12/28/2022] Open
Abstract
Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.
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Affiliation(s)
- Joseph C Anderson
- Department of Veterans Affairs Medical Center, White River Junction, VT, and The Geisel School of Medicine at Dartmouth Medical, Hanover, NH, USA
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16
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Sessile serrated polyps at screening colonoscopy: have they been under diagnosed? Am J Gastroenterol 2014; 109:1698-704. [PMID: 25001254 DOI: 10.1038/ajg.2014.78] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 03/20/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The sessile serrated adenoma/polyp (SSA/P) is increasingly recognized as an important precursor to colorectal cancer (CRC) and may contribute to proximal postcolonoscopy CRCs. Hyperplastic polyps (HPs) generally follow a more benign course than do SSA/Ps, but they have a similar histologic appearance. Our aims were to identify patient and polyp factors associated with reclassification of HPs as SSA/Ps during a central pathology review and to characterize and compare their subsequent clinical management with other polyps. METHODS From 2003 to 2008, we prospectively enrolled asymptomatic persons aged 50-74 years in a study of screening colonoscopy. Because criteria for SSA/P diagnosis evolved over our study period, we initiated a second review of all HPs >5 mm in size in 2011, with reclassification of polyps if indicated. Rates of subsequent colonoscopies, polypectomies, and CRCs were identified. RESULTS We enrolled 2,527 persons who underwent colonoscopy in whom 111 had HPs >5 mm. Thirty-two of the 111 participants (28.8%) with HPs >5 mm had their polyps reclassified as SSA/Ps. There were no significant differences in patient characteristics between those with reclassified SSA/Ps and those who had HPs >5 mm. SSA/Ps were more likely to be proximal (P<0.001) and larger (P<0.007) than the HPs. In all, 48.3% of those with high-risk adenomas received appropriate follow-up compared with 26.1% of those with high-risk SSA/Ps. CONCLUSIONS Almost 1/3 of recently diagnosed HPs >5 mm were reclassified as SSA/Ps. Patients previously diagnosed with larger HPs in the proximal colon may benefit from a pathologic review to ensure appropriate diagnosis and follow-up.
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Verseveld M, Barendse RM, Dawson I, Vos EL, de Graaf EJR, Doornebosch PG. Intramucosal carcinoma of the rectum can be safely treated with transanal endoscopic microsurgery; clinical support of the revised Vienna classification. Surg Endosc 2014; 28:3210-5. [PMID: 24939156 DOI: 10.1007/s00464-014-3593-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 05/06/2014] [Indexed: 12/19/2022]
Abstract
AIM The revised Vienna criteria were proposed for classifying rectal neoplasia and subsequent treatment strategies. Restaging intramucosal carcinoma to a non-invasive subgroup seems logical, but clinical support is lacking. In this study, we investigated whether distinction between intramucosal carcinomas (IMC) and rectal adenoma (RA) is of clinical relevance and whether these neoplasms can all be similarly and safely treated by transanal endoscopic microsurgery (TEM). METHODS All consecutive patients with IMC and RA, treated with TEM between 1996 and 2010 in tertiary referral centre for TEM were included. Long-term outcome of 88 IMC was compared to 356 pure rectal adenomas (RA). Local recurrence (LR) rate was the primary endpoint. Risk factors for LR were analysed. RESULTS LR was diagnosed in 7/88 patients (8.0 %) with IMC and in 33/356 patients with primary RA (9.3 %; p = 0.700) and LR-free survival did not differ (p = 0.438). Median time to recurrence was 10 months (IQR IMC 5-30; RA 6-16). Overall recurrence occurred mainly in the first 3 years (38/40; 95 %). None of the LR revealed malignancy on pathological evaluation. No differences could be found in complication rates (IMC 9 %; RA 13 %; p = 0.34). Metastases did not occur in either group. Independent risk factors for LR were irradical margins at final histopathology (HR 2.32; 95 % CI 1.17-4.59; p = 0.016) and more proximal tumours (HR 0.84; 95 % CI 0.77-0.92; P = <0.001). CONCLUSION In this study, IMC of the rectum and RA have similar recurrence rates. This supports the revised Vienna classification. Both entities can be safely treated with TEM.
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Affiliation(s)
- Maria Verseveld
- Department of Surgery, IJsselland Hospital, P.O. Box 960, Capelle aan den IJssel, The Netherlands,
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Tutticci NJ, Hewett DG, Leggett BA. Prevalence of serrated polyps: implications for significance as colorectal cancer precursors. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.70] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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20
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Serrated lesions and hyperplastic (serrated) polyposis relationship with colorectal cancer: classification and surveillance recommendations. Gastrointest Endosc 2013; 77:858-71. [PMID: 23684091 DOI: 10.1016/j.gie.2013.02.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 02/11/2013] [Indexed: 02/08/2023]
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21
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Kumbhari V, Behary J, Hui JM. Prevalence of adenomas and sessile serrated adenomas in Chinese compared with Caucasians. J Gastroenterol Hepatol 2013; 28:608-12. [PMID: 23278321 DOI: 10.1111/jgh.12100] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Colonic adenomas and sessile serrated adenomas (SSA) are the most common premalignant polyps identified at colonoscopy. This study compares the prevalence of neoplastic polyps in Chinese and Caucasians in a general gastroenterology outpatient practice in Australia. METHODS This study included consecutive unselected colonoscopies performed for standard clinical indications by a single endoscopist (JMH). All polyps detected were measured, resected, and sent for histopathology. The prevalence of adenomas, advanced adenomas, SSA, and cancer in the Chinese and Caucasian cohorts were compared. Advanced adenomas were defined as adenomas > 10 mm, villous histology, or high-grade dysplasia. RESULTS The study included 346 Chinese and 654 Caucasians. There was no significant difference in the baseline characteristics including age, gender, and indications of colonoscopy, although Chinese were more likely to present with rectal bleeding (22.8% vs 15.9%, P = 0.01). The prevalence of adenomatous polyps was similar in both Caucasians (34.3%) and Chinese (35.3%). However, advanced adenomas were more significantly common in Caucasians (11.3%) compared with Chinese (4.6%) (P < 0.001). SSA was rare in Chinese (2%) but present more frequently in Caucasians (7%) (P = 0.001). Multivariate analysis showed that Caucasian ethnicity (odds ratio 2.4, 95% confidence interval 1.6-3.6) and the presence of SSA (odds ratio 4.4, 95% confidence interval 2.3-8.6) were independent predictors for the detection of an advanced adenoma. CONCLUSIONS The prevalence of significant colorectal lesions, including advanced adenomas, large adenomas, and SSA, were lower in Chinese compared with Caucasians. These findings may influence the guidelines for colonic cancer screening in Chinese populations.
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Affiliation(s)
- Vivek Kumbhari
- Department of Gastroenterology, The Sutherland Hospital, Sydney, New South Wales, Australia
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22
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Liang JJ, Bissett I, Kalady M, Bennet A, Church JM. Importance of serrated polyps in colorectal carcinogenesis. ANZ J Surg 2012; 83:325-30. [DOI: 10.1111/j.1445-2197.2012.06269.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2012] [Indexed: 01/15/2023]
Affiliation(s)
- Jennifer J. Liang
- Department of Colorectal Surgery; Digestive Diseases Institute; Cleveland Clinic Foundation; Cleveland; Ohio; USA
| | - Ian Bissett
- Department of Colorectal Surgery; Digestive Diseases Institute; Cleveland Clinic Foundation; Cleveland; Ohio; USA
| | - Matthew Kalady
- Department of Colorectal Surgery; Digestive Diseases Institute; Cleveland Clinic Foundation; Cleveland; Ohio; USA
| | - Ana Bennet
- Department of Colorectal Surgery; Digestive Diseases Institute; Cleveland Clinic Foundation; Cleveland; Ohio; USA
| | - James M. Church
- Department of Colorectal Surgery; Digestive Diseases Institute; Cleveland Clinic Foundation; Cleveland; Ohio; USA
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23
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Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, Goldblum JR, Guillem JG, Kahi CJ, Kalady MF, O’Brien MJ, Odze RD, Ogino S, Parry S, Snover DC, Torlakovic EE, Wise PE, Young J, Church J. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012; 107:1315-29; quiz 1314, 1330. [PMID: 22710576 PMCID: PMC3629844 DOI: 10.1038/ajg.2012.161] [Citation(s) in RCA: 828] [Impact Index Per Article: 63.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
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Affiliation(s)
| | - Dennis J. Ahnen
- Staff Physician Denver VA Medical Center and Professor of Medicine, University of Colorado School of Medicine
| | | | | | - Carol A. Burke
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Randall W. Burt
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine
| | | | | | - Charles J. Kahi
- Indiana University School of Medicine; Richard L. Roudebush VA Medical Center
| | | | | | - Robert D. Odze
- Brigham and Womens Hospital, Department of Pathology, Harvard Medical School, Boston MA
| | - Shuji Ogino
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Susan Parry
- New Zealand Familial GI Cancer Registry, Auckland City Hospital, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
| | - Dale C. Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, MN
| | - Emina Emilia Torlakovic
- Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Paul E. Wise
- Department of Surgery, Vanderbilt University Medical Center
| | - Joanne Young
- Cancer Council Queensland Senior Research Fellow, Laboratory Head, Familial Cancer Laboratory, Australia
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Boparai KS, Hazewinkel Y, Dekker E. Serrated polyposis syndrome and the role of serrated polyps in colorectal cancer development. COLORECTAL CANCER 2012. [DOI: 10.2217/crc.11.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Serrated polyposis syndrome is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer risk. The mixture of distinct precursor lesion types and malignancies in serrated polyposis syndrome provides a unique model to study the recently proposed serrated neoplasia pathway. This pathway involves the progression of serrated polyps, that is, hyperplastic polyps, sessile serrated adenoma/polyps and/or traditional serrated adenomas, to colorectal cancer. The early genetic events of this route, as currently identified, are BRAF or KRAS mutations and an enhanced CPG island methylation status of multiple genes. There is evidence to suggest that a proportion of sporadic colorectal cancers originate from serrated polyps, which encompass molecular sequences of events such as hypermethylation of different genes and BRAF mutations. This review discusses the characteristics and clinical relevance of serrated polyps and provides an overview of the clinical aspects and treatment of serrated polyposis syndrome.
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Affiliation(s)
- Karam Singh Boparai
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Yark Hazewinkel
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
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Boparai KS, Dekker E, Polak MM, Musler AR, van Eeden S, van Noesel CJM. A serrated colorectal cancer pathway predominates over the classic WNT pathway in patients with hyperplastic polyposis syndrome. THE AMERICAN JOURNAL OF PATHOLOGY 2011; 178:2700-7. [PMID: 21641392 DOI: 10.1016/j.ajpath.2011.02.023] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2010] [Revised: 02/10/2011] [Accepted: 02/22/2011] [Indexed: 12/14/2022]
Abstract
Hyperplastic polyposis syndrome (HPS) is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer (CRC) risk. The mixture of distinct precursor lesion types and malignancies in HPS provides a unique model to study the canonical pathway and a proposed serrated CRC pathway in humans. To establish which CRC pathways play a role in HPS and to obtain new support for the serrated CRC pathway, we assessed the molecular characteristics of polyps (n = 84) and CRCs (n = 19) in 17 patients with HPS versus control groups of various sporadic polyps (n = 59) and sporadic microsatellite-stable CRCs (n = 16). In HPS and sporadic polyps, APC mutations were exclusively identified in adenomas, whereas BRAF mutations were confined to serrated polyps. Six of 19 HPS CRCs (32%) were identified in a serrated polyp. Mutation analysis performed in the CRC and the serrated component of these lesions showed identical BRAF mutations. One HPS CRC was located in an adenoma, both components harboring an identical APC mutation. Overall, 10 of 19 HPS CRCs (53%) carried a BRAF mutation versus none in control group CRCs (P = 0.001). Six BRAF-mutated HPS CRCs (60%) were microsatellite unstable owing to MLH1 methylation. These findings provide novel supporting evidence for the existence of a predominant serrated CRC pathway in HPS, generating microsatellite-stable and microsatellite-instable CRCs.
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Affiliation(s)
- Karam S Boparai
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Abstract
BACKGROUND Sessile serrated polyps are precursors of colorectal cancer arising from molecular pathways distinct from conventional adenomas. The association between sessile serrated polyps and conventional adenomas is not well known. OBJECTIVE We hypothesize that individuals who have coexistent sessile serrated polyps and conventional adenomas express a more severe phenotype than those harboring lesions from only one pathway. We compare colorectal phenotypes among individuals with sessile serrated polyps, those with conventional adenomas, and those expressing both. DESIGN This investigation is a retrospective cross-sectional study of 3 cohorts. SETTINGS This study was conducted in multiple centers within 1 health care system. PATIENTS Individuals with sessile serrated polyps and/or conventional adenomas on first lifetime colonoscopy were included in the study. MAIN OUTCOME MEASURES The demographics and polyp characteristics were compared among 3 cohorts to determine the differences in phenotypic expression. RESULTS Two hundred sixty individuals with sessile serrated polyps and 173 with only conventional adenomas were included. The disease phenotype was most severe in individuals with coexistent sessile serrated polyps and adenomas. The sessile serrated polyps in this cohort were larger (P = .01) than in the serrated-only cohort. The conventional adenomas in this cohort were more numerous (P = .035) and more advanced (P = .046) than in the adenoma-only cohort. Synchronous colorectal cancers were found exclusively in the cohorts with sessile serrated polyps, although this did not reach statistical significance (P = .06). LIMITATIONS Cross-sectional design precluded the ability to assess for metachronous lesions. Sessile serrated polyps, but not all polyps, were reviewed. CONCLUSIONS Individuals who coexpress sessile serrated polyps and conventional adenomas have an aggressive colorectal phenotype. They harbor larger sessile serrated polyps and more numerous and advanced adenomas than individuals with only sessile serrated polyps or adenomas. Synchronous colorectal cancers were found exclusively in cohorts with sessile serrated polyps. Individuals with sessile serrated polyps, especially with coexistent conventional adenomas, appear to be a high-risk group, which needs to be accounted for when calculating postpolypectomy surveillance intervals.
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Leonard DF, Dozois EJ, Smyrk TC, Suwanthanma W, Baron TH, Cima RR, Larson DW. Endoscopic and surgical management of serrated colonic polyps. Br J Surg 2011; 98:1685-94. [PMID: 22034178 DOI: 10.1002/bjs.7654] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND Serrated polyps are an inhomogeneous group of lesions that harbour precursors of colorectal cancer. Current research has been directed at further defining the histopathological characteristics of these lesions, but definitive treatment recommendations are unclear. The aim was to review the current literature regarding classification, molecular genetics and natural history of these lesions in order to propose a treatment algorithm for surgeons to consider. METHODS The PubMed database was searched using the following search terms: serrated polyp, serrated adenoma, hyperplastic polyp, hyperplastic polyposis, adenoma, endoscopy, surgery, guidelines. Papers published between 1980 and 2010 were selected. RESULTS Sixty papers met the selection criteria. Most authors agree that recommendations regarding endoscopic or surgical management should be based on the polyp's neoplastic potential. Polyps greater than 5 mm should be biopsied to determine their histology so that intervention can be directed accurately. Narrow-band imaging or chromoendoscopy may facilitate the detection and assessment of extent of lesions. Complete endoscopic removal of sessile serrated adenomas in the left or right colon is recommended. Follow-up colonoscopy is recommended in 2-6 months if endoscopic removal is incomplete. If the lesion cannot be entirely removed endoscopically, segmental colectomy is strongly recommended owing to the malignant potential of these polyps. Left-sided lesions are more likely to be pedunculated, making them more amenable to successful endoscopic removal. CONCLUSION Even though the neoplastic potential of certain subtypes of serrated polyp is heavily supported, further studies are needed to make definitive endoscopic and surgical recommendations.
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Affiliation(s)
- D F Leonard
- Division of Colon and Rectal Surgery, Department of Anatomic Pathology, Division of Gastroenterology, Mayo Clinic, Gonda 9 South, 200 First Street SW, Rochester, Minnesota 55905, USA
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Patel VG, Darko ND, Martin DM, Lyons R, Marantz D. Serrated Adenoma of the Colon: An Under-Recognized Premalignant Variant of Adenomatous Polyp. Am Surg 2010. [DOI: 10.1177/000313481007600920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
| | - Nii-Daako Darko
- Department of Surgery Morehouse School of Medicine East Point, Georgia
| | | | - Ralph Lyons
- South Fulton Medical Center Atlanta, Georgia
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Abstract
Until very recently, there was general acceptance in the pathology community that all serrated lesions of the colon and rectum without overt cytologic dysplasia were hyperplastic polyps and had no malignant potential. Although there are still several unanswered questions in regard to the relationship between the various serrated lesions, there is a better understanding of the relationship of sessile serrated adenoma to carcinoma. This article discusses hyperplastic polyps, sessile serrated adenoma, traditional serrated adenoma, mixed polyps, and serrated lesions in such conditions as idiopathic inflammatory bowel disease and mechanical trauma. The major focus of the content is on diagnostic features of these lesions.
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Affiliation(s)
- Dale C Snover
- Department of Pathology, Fairview Southdale Hospital, 6401 France Avenue South, Edina, MN 55435-2199, USA; Department of Laboratory Medicine and Pathology, The University of Minnesota Medical School, Minneapolis, Mayo Mail Code 609, 420 Delaware Street SE, Minneapolis, MN 55455, USA
| | - Kenneth P Batts
- Department of Laboratory Medicine and Pathology, The University of Minnesota Medical School, Minneapolis, Mayo Mail Code 609, 420 Delaware Street SE, Minneapolis, MN 55455, USA; Department of Pathology and Laboratory Medicine, and Virginia Piper Cancer Center, Abbott Northwestern Hospital, 800 East 28th Street, Minneapolis, MN 55407, USA; Hospital Pathology Associates, PA, 2345 Rice Street, Suite 160, Saint Paul, MN 55113-3769, USA.
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30
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Noffsinger AE, Hart J. Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia? Gastrointest Endosc Clin N Am 2010; 20:543-63. [PMID: 20656251 DOI: 10.1016/j.giec.2010.03.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Until recently, 2 major forms of colorectal polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were known to represent a precursor to colorectal cancer, whereas hyperplastic polyps were viewed as nonneoplastic, having no potential for progression to malignancy. We now recognize, however, that the lesions diagnosed as hyperplastic polyps in the past represent a heterogeneous group of polyps, some of which truly are hyperplastic, and others that truly have a significant risk for transformation to colorectal cancer. These polyps have a characteristic serrated architecture, and include not only hyperplastic polyps but also the recently recognized serrated adenomas. Serrated adenomas occur in 2 forms: the traditional serrated adenoma, which is usually a polypoid lesion endoscopically, and the sessile serrated adenoma, a flat or slightly raised, usually right-sided lesion. Serrated adenomas of both types show characteristic molecular alterations not commonly seen in traditional colorectal adenomas, and probably progress to colorectal cancer by means of a different pathway, the so-called serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed.
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Affiliation(s)
- Amy E Noffsinger
- Department of Pathology, University of Cincinnati, PO Box 670529, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
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Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2009; 4:343-64. [PMID: 19400693 DOI: 10.1146/annurev.pathol.4.110807.092317] [Citation(s) in RCA: 161] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colorectal cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed herein.
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Affiliation(s)
- Amy E Noffsinger
- Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
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Abstract
The fundamental view that colon adenocarcinomas arise only from conventional adenomas has been challenged by the now recognized hyperplastic polyp-serrated adenoma-adenocarcinoma pathway. This article describes the history of the serrated adenoma (both the traditional serrated adenoma and the sessile serrated adenoma) as well as the histology and endoscopic appearance of these lesions in comparison with hyperplastic polyps and mixed polyps. Although the exact pathway is the subject of ongoing research, compelling histologic associations and molecular phenotypes that define the model of the serrated polyp-carcinoma sequence, including microsatellite instability, BRAF/KRAS mutations, and CpG island methylator phenotype, provide strong evidence that this is a genuine pathway. Management of serrated neoplasia of the colon includes careful colonoscopy, complete removal of colonic polyps, sampling fields of diminutive polyps of the rectosigmoid, and basing surveillance on histology of removed polyps.
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Affiliation(s)
- Rachel J Groff
- University of Colorado Denver School of Medicine, Denver, CO 80220, USA
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Serrated adenoma is a risk factor for subsequent adenomatous polyps. Dig Dis Sci 2008; 53:2204-7. [PMID: 18320324 DOI: 10.1007/s10620-007-0143-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Accepted: 11/24/2007] [Indexed: 12/09/2022]
Abstract
BACKGROUND Serrated adenomas (SA) are histologically defined by the presence of both hyperplastic and adenomatous features. These uncommon polyps are thought to play an important role in the development of sporadic colorectal cancers (CRC) with microsatellite instability (MSI). There is paucity of data on the risk of progression of SA to CRC. This study was undertaken to define the relationship between SA and the future development of adenomatous polyps. METHODS Colonoscopic biopsies that contained a pathologic diagnosis of SA were identified from a pathology database of a major urban academic medical center. Those patients with absence of concomitant malignancy, complete colonoscopy, good or adequate prep and presence of at least one follow-up procedures were identified. These were matched to controls by age, sex, indication for colonoscopy, polyp type and number and duration of follow-up. Outcomes of the follow-up procedures were compared. RESULTS Between January 1997 and June 2005 17,226 colonoscopic biopsies and polypectomies were performed. Of these, 80 patients (0.5%) with SA were found, and of these SA, 80% were found in the left colon. The average age of patients undergoing colonoscopy was 58.5 years, and the average age of patients with SA was 68 years (P = 0.004). Of all patients with SA, 7 (9%) had concomitant CRC. The final groups contained 17 patients and 17 controls, respectively, and were well matched. The mean follow-up interval in the patient group was 29 months vs. 31 months in the control group (P = 0.82). On follow-up examination four patients (24%) and no controls had adenomatous polyps (P = 0.01). CONCLUSIONS While SA are uncommon, they are commonly associated with colorectal cancer. Serrated adenomas appear to be found more commonly in the left colon and in older patients. This study found a significant association between SA and the subsequent development of adenomatous polyps. Further studies are needed to define appropriate preventive strategies for these patients.
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Konda A, Duffy MC. Surveillance of patients at increased risk of colon cancer: inflammatory bowel disease and other conditions. Gastroenterol Clin North Am 2008; 37:191-213, viii. [PMID: 18313546 DOI: 10.1016/j.gtc.2007.12.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States. Colonoscopic screening with removal of adenomatous polyps in individuals at average risk is known to decrease the incidence and associated mortality from colon cancer. Certain conditions, notably inflammatory bowel disease involving the colon, a family history of polyps or cancer, a personal history of colon cancer or polyps, and other conditions such as acromegaly, ureterosigmoidostomy, and Streptococcus bovis bacteremia are associated with an increased risk of colonic neoplasia. This article reviews the CRC risks associated with these conditions and the currently recommended surveillance strategies.
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Affiliation(s)
- Amulya Konda
- Division of Gastroenterology, William Beaumont Hospital, 3535 West 13 Mile Road, Royal Oak, MI 48076, USA
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Summerton S, Little E, Cappell MS. CT colonography: current status and future promise. Gastroenterol Clin North Am 2008; 37:161-viii. [PMID: 18313545 DOI: 10.1016/j.gtc.2007.12.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CT colonography (CTC) is an innovative technology that entails CT examination of the entire colon and computerized processing of the raw data after colon cleansing and colonic distention. CTC could potentially increase the screening rate for colon cancer because of its relative safety, relatively low expense, and greater patient acceptance, but its role in mass colon cancer screening is controversial because of its highly variable sensitivity, the inability to sample polyps for histologic analysis, and lack of therapeutic capabilities. This article reviews the CTC literature, including imaging and adjunctive techniques, radiologic interpretation, procedure indications, contraindications, risks, sensitivity, interpretation pitfalls, and controversies.
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Affiliation(s)
- Susan Summerton
- Department of Radiology, Albert Einstein Medical Center, 5501 Old York Road, Philadelphia, PA 19141, USA.
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Song SY, Kim YH, Yu MK, Kim JH, Lee JM, Son HJ, Rhee PL, Kim JJ, Paik SW, Rhee JC. Comparison of malignant potential between serrated adenomas and traditional adenomas. J Gastroenterol Hepatol 2007; 22:1786-90. [PMID: 17914951 DOI: 10.1111/j.1440-1746.2006.04356.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas. METHODS A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of > or =20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma. RESULTS The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high-grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high-grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high-grade dysplasia and carcinoma. CONCLUSIONS Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.
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Affiliation(s)
- Sang Yong Song
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
Serrated polyps of the colorectum form a group of related lesions which include aberrant crypt foci (ACF), conventional hyperplastic polyps, mixed (admixed) polyps, serrated adenomas and sessile serrated adenomas. In recent years the molecular differences between these morphologically similar lesions have been highlighted, and their differing biological potential has been realised. In particular, the sessile serrated adenoma has become recognised as the precursor lesion to a group of sporadic colorectal carcinomas characterised by morphological and molecular features distinct from conventional adenomas. These recent findings have challenged the long held paradigm that all colorectal carcinomas arise via the traditional adenoma-carcinoma sequence. In addition, they present a major challenge for the early detection and management of colorectal cancer, which is no longer regarded as a homogeneous entity.
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Affiliation(s)
- Nathan T Harvey
- Division of Tissue Pathology, Institute of Medical and Veterinary Science, Frome Rd, Adelaide 5000, Australia.
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Watson AR, Jankowski J. Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway. CURRENT COLORECTAL CANCER REPORTS 2007. [DOI: 10.1007/s11888-007-0009-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Abstract
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in most Western countries. Serrated adenocarcinoma is a recently described, distinct variant of CRC, accounting for about 7.5% of all CRCs and up to 17.5% of most proximal CRCs. It has been postulated that about 10-15% of sporadic CRCs would have their origin in serrated polyps that harbour a significant malignant potential. These lesions include hyperplastic-type aberrant crypt foci, hyperplastic polyps, sessile serrated adenomas, admixed polyps and serrated adenomas, and constitute the so-called 'serrated pathway', which is distinct from both the conventional adenoma-carcinoma pathway and the mutator pathway of hereditary non-polyposis CRC and is characterized by early involvement of oncogenic BRAF mutations, excess CpG island methylation (CIM) and subsequent low- or high-level DNA microsatellite instability (MSI). Methylation of hMLH1 is likely to explain the increased frequency of high-level MSI (16%) and methylation of MGMT is postulated to explain the low-level MSI (29%) in serrated adenocarcinomas. Reproducible histopathological criteria for serrated adenocarcinoma have recently been established and they have been qualified by DNA expression analysis for 7928 genes, showing clustering of serrated adenocarcinomas into a molecular entity apart from conventional adenocarcinoma, and representing with distinct down-regulation of EPHB2, PTCH and up-regulation of HIF1alpha.
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Affiliation(s)
- M J Mäkinen
- Department of Pathology, University of Oulu, Oulu, Finland.
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Sheridan TB, Fenton H, Lewin MR, Burkart AL, Iacobuzio-Donahue CA, Frankel WL, Montgomery E. Sessile serrated adenomas with low- and high-grade dysplasia and early carcinomas: an immunohistochemical study of serrated lesions "caught in the act". Am J Clin Pathol 2006; 126:564-71. [PMID: 16938659 DOI: 10.1309/c7je8bvl8420v5vt] [Citation(s) in RCA: 123] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Sessile serrated adenomas (SSAs) show serrations typical of hyperplastic polyps but display architectural differences and lack traditional dysplasia. SSAs with foci of low- (LGD) or high-grade dysplasia (HGD) or early invasive carcinoma are seldom biopsied and, thus, are not well studied. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 (mismatch repair gene products) was performed on colon biopsy specimens from 11 patients (age range, 54-87 years; 4 men and 7 women) showing SSA with LGD (n = 1), HGD (n = 5), or focal invasive carcinoma (n = 5). All 11 cases showed intact nuclear staining for MSH2 and MSH6 in the SSA component; in foci of LGD, HGD, or carcinoma; and in background normal mucosa. In contrast, there was tandem loss of MLH1 and PMS2 in zones of LGD (1/1) or HGD (3/5) and early carcinoma (2/4; with concordant loss in associated HGD) but retention in SSA areas (11/11) and normal mucosa (11/11). No patient was known to have hereditary nonpolyposis colorectal cancer/Lynch syndrome. This study offers additional strong evidence that SSA is truly a precursor to at least a subset of sporadic microsatellite-unstable colorectal cancer.
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Affiliation(s)
- Todd B Sheridan
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 21231-2401, USA
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Abstract
Serrated polyps of the large intestine comprise a family of lesions bearing some histological similarities, including an overall serrated configuration caused at least in part by inhibition of apoptosis by mutations in one of two genes. Over the past decade, it has become apparent that these lesions can be subdivided by histological criteria into lesions with differing degrees of relationship to the development of carcinoma, including sporadic microsatellite instable (MSI) carcinomas and probably carcinomas demonstrating the CpG island methylator phenotype (CIMP), which includes both MSI and microsatellite stable tumors. These differing histological subtypes can in part predict some of the molecular features of these lesions, and the combination of histological and molecular features is beginning to give us better insight into the potential natural history and therefore management of these lesions. This review will present the histological classification of these lesions, relate that histological classification to molecular aspects of the lesions, and present recommendations for management.
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Affiliation(s)
- Dale C Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, Minnesota 55435, USA.
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Chow E, Lipton L, Lynch E, D'Souza R, Aragona C, Hodgkin L, Brown G, Winship I, Barker M, Buchanan D, Cowie S, Nasioulas S, du Sart D, Young J, Leggett B, Jass J, Macrae F. Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH. Gastroenterology 2006; 131:30-9. [PMID: 16831587 DOI: 10.1053/j.gastro.2006.03.046] [Citation(s) in RCA: 123] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2005] [Accepted: 03/23/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. METHODS Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. RESULTS Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. CONCLUSIONS Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.
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Affiliation(s)
- Elizabeth Chow
- Familial Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
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Abstract
Serrated neoplasia of the gastro-intestinal tract have peculiar microscopic and molecular features that are still incompletely described. Some serrated polyps seem to be involved in a new carcinogenic pathway in the colon: the serrated neoplasia pathway, with hypermethylation of the cytosine-guanine dinucleotides, located in the promoter of some genes such as h-MLH1, BRAF and MGMT. The natural history of the serrated polyps and their risk for progression to malignancy are still unclear. There is no official guideline for the management of serrated polyps. The aim of this article is to describe the epidemiological, morphological, immunohistochemical and molecular characteristics of the serrated neoplasia of the gastrointestinal tract: hyperplastic polyps, "traditional" serrated adenomas, mixed hyperplastic and adenomatous polyps, sessile serrated adenomas, hyperplastic polyposis and serrated adenocarcinomas.
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Affiliation(s)
- Denis Chatelain
- Service d'Anatomie Pathologique, CHU Amiens, Place Victor Pauchet, 80000 Amiens Cedex 01
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45
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Abstract
AIM: To study the association of colorectal serrated adenomas (SAs) with invasive carcinoma, local recurrence, synchronicity and metachronicity of lesions.
METHODS: A total of 4536 polyps from 1096 patients over an eight-year period (1987-1995) were retrospectively examined. Adenomas showing at least 50% of serrated architecture were called SAs by three reviewing pathologists.
RESULTS: Ninety-one (2%) of all polyps were called SAs, which were found in 46 patients. Invasive carcinomas were seen in 3 out of 46 (6.4%) patients, of whom one was a case of familial adenomatous polyposis (FAP). A male preponderance was noted and features of a mild degree of dysplasia were seen in majority (n=75, 83%) of serrated adenomas. Follow-up ranged 1-12 years with a mean time of 5.75 years. Recurrences of SAs were seen in 3 (6.4%) cases, synchronous SAs in 16 (34.8%) cases and metachronous SAs in 9 (19.6%) cases.
CONCLUSION: Invasive carcinoma arising in serrated adenoma is rare, accounting for 2 (4.3%) cases studied in this series.
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Affiliation(s)
- Ashish Chandra
- Department of Pathology, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, United Kingdom
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Abstract
Serrated adenomas (SA) of the colorectum show features intermediate between hyperplastic polyps (HP) and adenomas. HP and SA are related lesions and there is now strong evidence for a 'serrated-polyp pathway' to colorectal cancer (CRC) that is largely independent of the classic adenoma-to-carcinoma sequence. A recently recognized lesion in this pathway is a HP variant characterized by relatively large size, atypical histology and proximal location in the colorectum. This HP variant has been given a variety of names in the literature including 'sessile SA' and 'type I SA'. Because this lesion lacks the traditional cytology of colorectal adenoma and in order to avoid confusion with SA, it is referred to in this review as sessile serrated polyp. SA are characterized by a heterogeneous group of changes at the molecular level, but a high proportion have BRAFmutations and DNA methylation. They may develop in HP or sessile serrated polyps, or may arise de novo. In the serratedpolyp pathway, the advent of genetic instability is likely to be an important rate-limiting step that drives rapid neoplastic evolution. Methylation and inactivation of the DNA repair genes MLH1 and MGMT (O-6-methylguanine-DNA methyltransferase) have been proposed as critical steps leading to genetic instability. Stretches of DNA rich in the bases guanine and cytosine (CpG islands; where p represents a phosphodiester bond linking adjacent cytosine and guanine bases) that are normally unmethylated may become methylated in malignant human colorectal tumors. Subsets of colorectal cancers with an unusually high number of methylated CpG islands have been described as having the 'CpG-island-methylator phenotype' It is possible that many, if not all, CRCs with the CpG-island-methylator phenotype evolve through the serrated-polyp pathway that would, therefore, explain approximately 20% of all CRCs. The current lack of guidelines for managing serrated polyps may explain the static incidence of proximal CRC, despite the falling incidence rates for left-sided CRC during the same time period.
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Affiliation(s)
- Jeremy R Jass
- Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Quebec H3A 2B4, Canada.
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Yashiro M, Laghi L, Saito K, Carethers JM, Slezak P, Rubio C, Hirakawa K, Boland CR. Serrated adenomas have a pattern of genetic alterations that distinguishes them from other colorectal polyps. Cancer Epidemiol Biomarkers Prev 2005; 14:2253-6. [PMID: 16172239 DOI: 10.1158/1055-9965.epi-04-0790] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Serrated adenomas are characterized by serrated crypts with dysplasia, and are distinguished from other polyps by their histology, but the genetic basis of serrated adenomas is unknown. We investigated genetic alterations in colorectal polyps to determine if a specific pattern were associated with serrated adenomas. METHODS Sixty-six small (<10 mm) colorectal polyps were studied, including 11 hyperplastic polyps, 27 serrated adenomas, 9 tubular adenomas, 6 tubulovillous adenomas, and 3 villous adenomas. Allelic imbalance and microsatellite instability were detected by analysis of microsatellites on 5q, 18q, 17p, 2p, and 3p; K-ras mutations were detected by oligonucleotide hybridization. RESULTS Each polyp subset had its own characteristic mutational signature. Allelic imbalance of 18q was significantly more common (P < 0.05), whereas allelic imbalance of 5q and K-ras mutations were significantly less common (P < 0.05) in serrated adenomas compared with other polyps. Allelic imbalance of 17p was not found in any polyp. CONCLUSIONS Serrated adenomas are significantly more likely to have allelic imbalance at 18q than other types of adenomas, and significantly less likely to have allelic imbalance at 5q or K-ras mutations. Serrated adenomas seem to evolve through a different genetic pathway than other types of polyps in the colon.
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Beach R, Chan AOO, Wu TT, White JA, Morris JS, Lunagomez S, Broaddus RR, Issa JPJ, Hamilton SR, Rashid A. BRAF mutations in aberrant crypt foci and hyperplastic polyposis. THE AMERICAN JOURNAL OF PATHOLOGY 2005; 166:1069-75. [PMID: 15793287 PMCID: PMC1602378 DOI: 10.1016/s0002-9440(10)62327-9] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Patients with hyperplastic polyposis have multiple hyperplastic polyps (HPs) and increased risk of colorectal carcinomas. Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesions in colorectal carcinogenesis. We evaluated BRAF mutations by DNA sequencing in 53 ACF from patients with sporadic colorectal carcinomas and familial adenomatous polyposis, in 18 sporadic HPs from patients with resected colorectal cancer, and in 70 HPs, 4 serrated adenomas, 3 admixed hyperplastic-adenomatous polyps, 10 tubular adenomas, and 6 carcinomas from 17 patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status was compared with clinicopathological features and other genetic alterations by marginal logistic regression. BRAF mutation was present in only 2% of ACF and 6% of sporadic HPs. In contrast, BRAF mutation was present in 43% of HPs (P = 0.01 versus sporadic HPs), 75% of serrated adenomas, 33% of admixed hyperplastic-adenomatous polyps, 30% of tubular adenomas, and 33% of carcinomas from patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status in patients with multiple/large HPs and/or hyperplastic polyposis correlated with HPs from the same patient (odds ratio, 5.8; P = 0.0002) but associated with younger age (odds ratio, 0.83; P = 0.006 compared to older age), with a large HP (odds ratio, 22.5; P = 0.01 compared with patients with multiple HPs), with location of HPs in the right colon (odds ratio, 3.0; P = 0.03), and with methylation of the p16 gene and the MINT31 locus [odds ratio, 12.2 (P = 0.0001) and 4.4 (P = 0.02), respectively]. Our study shows that BRAF mutation status is heterogeneous among patients with multiple/large HPs and/or hyperplastic polyposis, suggesting differences in pathogenesis of HPs that indicate subsets within this phenotype.
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Affiliation(s)
- Robyn Beach
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4095, USA
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Misdraji J. Epithelial neoplasms and other epithelial lesions of the appendix (excluding carcinoid tumours). ACTA ACUST UNITED AC 2005. [DOI: 10.1016/j.cdip.2004.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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50
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Stellakis MLC, Reddy KM, Arnaout A, Swift RI. Hyperplastic polyps and serrated adenomas: colonoscopic surveillance? Surgeon 2004; 2:112-4. [PMID: 15568437 DOI: 10.1016/s1479-666x(04)80055-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Hyperplastic polyps are not thought to carry a malignant potential. They are, therefore, not regularly screened by the majority of clinicians. We present two case reports of serrated adenomas that add to a small but expanding body of clinical and histological evidence that suggests a hyperplastic to neoplastic pathway. Regular colonoscopic surveillance may be indicated in at least some cases of hyperplastic polyposis
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Affiliation(s)
- M L C Stellakis
- Colorectal Unit, Mayday University Hospital, 530 London Road, Croydon, London CR7 7YE.
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