SERRATED POLYPS/AENOMA OF THE COLON AND RECTUM
: 1. Colon and rectal cancers molecular pathways
2. Colon and rectum polyps 3. Colon and rectum Serrated polyps/adenomas 4. Colon and rectal Serrated polyps/adenomas Management Over the last 20 years it has become clear that colorectal cancer (CRC) evolves through multiple pathways. REVIEW Classification of colorectal cancer based on correlation of clinical, morphological and molecular features Histopathology 2007, 50, 113130. DOI: /j x colorectal cancer (CRC) evolves through multiple pathwaysAdvanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a fusion pathway to colorectal cancer 2006 The Authors. Journal compilation 2006 Blackwell Publishing Ltd, Histopathology, 49, 121131. Adenoma-Carcinoma Sequence APC gene Serrated polyp-cancer pathway. BRAF (gene) Concept of fusion pathways to CRC These pathways may be defined on the basis of two molecular features: Histopathology 2007, 50, 113130. DOI: /j x (i) DNA microsatellite instability (MSI) status stratified asMSI-high (MSI-H), MSI-low(MSI-L) and MSstable (MSS), and (ii) CpG island methylator phenotype (CIMP) stratified as CIMPhigh,CIMP low and CIMP-negative (CIMPneg). This approach to the classification of CRC should accelerate understanding of causation and will impact on clinical management in the areas of both prevention and treatment. Serrated polyps are the precursors
In this review the morphological correlates of five molecular subtypes are outlined:REVIEW Classification of colorectal cancer based on correlation of clinical, morphological and molecular featuresHistopathology 2007, 50, 113130. Serrated polyps are the precursors Type 1 (CIMP-high MSI-H BRAF mutation), (12%). Type 2 (CIMP-high MSI-L or MSS BRAF mutation), (8%). Either: Type 3 (CIMP-low MSS or MSI-L KRAS mutation), (20%). adenomacarcinoma sequence. Type 4 (CIMP-neg MSS) (57% ). and Type 5 or Lynch syndrome (CIMP-neg MSI-H) 3%. This approach to the classification of CRC should accelerate understanding of causation and will impact on clinical management in the areas of both prevention and treatment. Histopathology 2007, 50, 113130. DOI: /j x Colorectal polyps neoplastic or non-neoplastic.
can be classified as neoplastic or non-neoplastic. Neoplastic polyps are subclassified into the following types: Adenomas (most common, with a risk of progression to carcinoma) Polypoid adenocarcinomas Lipomas, leiomyomas, and lymphomatous polyps (the less-common carcinoid tumours). Non-neoplastic polyps
are subclassified into the following types: Hyperplastic polyps (always benign) Inflammatory polyps (usually in ulcerative colitis and occasionally in Crohn's disease) Lymphoid polyps or hamartomas (a benign overgrowth of tissues normally found at the site; e.g., Peutz-Jeghers syndrome). Neoplastic (adenomas) Describe the current general classification of colon polyps. Which features of an adenomatous polyp correlate with greater malignant potential? Clin Med Res. Jul 2003; 1(3): 261262 Tubular adenomas (0-25% villous tissue) Tubulovillous adenomas (25-75% villous tissue) Villous adenoma (75-100% villous tissue) All types of adenomas are dysplastic and pre-malignant, although adenomas with a significant villous component are more likely to become malignant. Malignant potential is associated with 1.degree of dysplasia
When does a polyp become a problem?From Wikipedia, the free encyclopedia Malignant potential is associated with 1.degree of dysplasia 2. Type of polyp (e.g. villous adenoma): Tubular Adenoma: 5% risk of cancer Tubulovillous adenoma: 20% risk of cancer Villous adenoma: 40% risk of cancer 3.Size of polyp: > MPHP Sessile serrated adenoma/polyp(SSA/P)
5-25% of all serrated polyps In one prospective study, 9% of all patients undergoing screening colonoscopy Precursor to sporadic carcinomas with microsatellite instability (MSI) Probably the precursor for CpG island-methylated microsatellite-stable carcinomas Histology of SSA/P Serration may be very prominent and is often seen at the base of the crypts The crypts are often dilated with abnormal shapes including L-shaped and inverted T-shaped Goblet-cell or gastric-foveolar differentiation at the base of the crypts Some areas of SSA/P may have straight crypts similar to those of MVHP Cytological dysplasia in SSA/P
Cytological dysplasia is not present in uncomplicated SSA/P Present while progression toward carcinoma Dysplasia resemble that of conventional adenomas "mixed SSA/P-tubular adenomas" (or mixed HP-TA) in the older literature "SSA/P with cytological dysplasia" is preferred SSA/P with cytological dysplasia
Often in conjunction with methylation of the MLH1 gene and with the development of MSI Biologically the cytologically, dysplastic part of these lesions is not the same as conventional adenoma The behaviour of these lesions may be more aggressive than that of conventional adenoma. Traditional serrated adenoma (TSA)
Uncommon, < 1 % of all polyps Complex and villiform growth pattern TSA is generally not associated with carcinoma with high MSI but may be associated with low MSI Cells showing cytological features different from the dysplasia of conventional adenomas or of SSA/P with cytological dysplasia Histology of TSA Narrow pencillate nucleus and eosinophilic cytoplasm
"ectopic" crypts : crypts lost their anchoring to the underlying muscularis mucosae Conventional dysplasia can occur in TSA, reflecting progression toward carcinoma Serrated polyp, unclassified
Distinction of HP from SSA/P and TSA is based mainly on architectural criteria Not all serrated lesions are easily classified, often because of sampling issues or poor orientation of the specimen. "serrated polyp, unclassified may be used Serrated adenoma? "serrated adenoma" was initially coined for any lesion showing serration and cytological dysplasia TSA SSA/P with cytological dysplasia Conventional adenomas with serrated architecture Because of this potentially confusing ambiguity, it is recommended that the term "serrated adenoma" never be used without a qualifier Serrated polyps at VGHKS
Hyperplastic polyp: 6970 (95.6%) Serrated adenoma: 319 (4.4%) SSA: 56 (17.5%) TSA: 66 (20.7%) Without qualifier: 197 (61.8%) Terminology for Reporting Serrated Polyps of the Large Intestine Am J Clin Pathol 2005;124:380-391
1. Hyperplastic polyp Microvesicular type (optional) Goblet cellrich type (optional) Mucin-poor type (optional) 2. Sessile serrated adenoma 3. Traditional serrated adenoma 4. Mixed serrated polyp (list individual components in parentheses, eg, mixed sessile serrated adenomatubular adenoma) 5. Sessile serrated polyp (with a comment that this is an equivocal diagnosis that includes both hyperplastic polyp and sessile serrated adenoma; one should try to favor 1 or the other in the comment, based on the location and size of the lesion, eg, large right-sided lesions favor SSA, small left-sided lesions favor HPP) HYPERPLASTIC POLYP ,The benign hyperplastic polyp
Management of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s HYPERPLASTIC POLYP ,The benign hyperplastic polyp accounts for 80 to 90% of serrated polyps. SESSILE SERRATED ADENOMA , SSA is recognized as the most common of the serrated adenomas accounting for 15 to 20% serrated polyps TRADITIONAL SERRATED ADENOMA, The TSA is very rare,constituting less than 1% of all colorectal polyps. MIXED POLYP The mixed polyp variant displays features of hyperplastic polyp and SSA, and a dysplastic component resembling conventional adenoma Serrated Polyps of the Large Intestine A Morphologic and Molecular Review of an Evolving ConceptAm J Clin Pathol 2005;124: Serrated polyps of the large intestine, including traditional hyperplastic polyps, traditional serrated adenomas, and more recently described sessile serrated adenomas, have gained increased recognition in recent years because of growing evidence that one of these lesions, the sessile serrated adenoma, might be the precursor lesion for some cases of microsatellite unstable colorectal carcinoma. PrevalenceThe clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 In one large study of over 7000 screening colonoscopies done by 13 endoscopists, the prevalence of adenomas was 22%, HP 12% and SSP 0.6% (18). Another study in over 3000 screening colonoscopies from 66 endoscopists demonstrated the SSP detection rate was 2% Risk to the individual with SSA The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Individuals who harbor serrated neoplasms are at in increased risk of synchronous serrated lesions as well as AN (21-25) (advanced conventional neoplasia ). Li et al found that both right and left sided, large serrated polyps are associated with a 3 fold risk of synchronous AN (22) Patients with either a proximal or large HP or SSP were found to be at increased risk of synchronous AN versus those without those lesions Risk to the individual with SSA The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Vu et al : The data demonstrated that individuals who co-express SSP and conventional adenomas have significantly more numerous, larger, SSPs and conventional adenomas and more pathologically advanced conventional adenomas than individuals with only SSA or conventional adenomas. Synchronous CRCs were found exclusively in the cohorts with SSA. In another study which identified polyps from pathology archives and assessed the clinical follow up found the incidence of CRC was higher in the SSP patients (12.5%) than in patients with HP (2%) or adenomatous polyps (2%) (33). Risk to the individual with SSAvsscreening and surveillance colonoscopyThe clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 The current target of screening and surveillance colonoscopy is the detection and prevention of metachronous advanced conventional neoplasia (AN) (tubular, tubulovillous [TVA], and villous [VA]). Advanced neoplasms are adenomas that are one centimeter or greater in size, harbor any villous component (TVA or VA), high grade dysplasia or invasive adenocarcinoma. Little is known about the risk of metachronous lesions in individuals with serrated colon polyps. colonoscopy on CRC incidence and mortality
1. COLONOSCOPIC EXAMINATIONAS SYMPTOMS / SIGNS. 2. REGULAR FOLLOW-UP EXAMINATION. 3. PHYSICAL CHECK-UP EXAMINATION. variable protection from the use of colonoscopy on CRC incidence and mortalityThe clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 a reduction of CRC mortality by up to 53% (6). variable protection from the use of colonoscopy on CRC incidence and mortality a decrease in overall and left sided CRC mortality, a lesser benefit of colonoscopy in the reduction of CRC mortality in the proximal colon. Interval cancers have been shown to occur in up to 9% of individuals with CRC who have undergone colonoscopy in the preceding 3 years the variable protection from colonoscopy and interval cancer The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Factors directly associated with the endoscopist : The specialty of the provider: 1. in particular procedures done by a non- gastroenterologist, or 2. by an endoscopist with low rates of adenoma detection,polypectomy or cecal intubation (10,12). Other factors include 1. the technical limitations of the exam, 2missed or insufficient resection of lesions, 3inadequatebowel preparation, and 4. the varying biologic behavior of lesions. Interval cancer The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Interval cancers, which are cancers which develop after a colonoscopy and before the next recommended interval, are of increasing recognition and concern.(or within 5 yrs) The factors most likely to becontributing to interval cancer is 1. the variability in the detection of SSP by the endoscopist and 2. inadequate resection of those lesions. 95
95 3.5 Variability in recognition and diagnosis of SSP (2-1) The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Recent data shows a significant variability in the ability of an endoscopist to detect an SSP. Kahi et al. found a 3 fold difference in adenoma detection rate and 18 fold variability in the detection of at least one proximal serrated polyp (26). Data from Hetzel et al. showed a 7 fold difference in SSP detection rate while the variability in adenoma detection was less than a 3 fold difference (18). Variability in recognition and diagnosis of SSP (2-2) The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 They also showed that SSP detection rates increased over time; being 0.6% in 2006 and increasing to 1.1% of exams in 2008. This may be due to an increasing awareness of the clinical importance of SSP by the endoscopist or even increasing ability to diagnose these lesions by the pathologist. Polyp Size Location Dysplasia Malignant Mutation Potential
Table 1 Histologic and Genetic Characteristics of Serrated Polyps Management of Serrated Adenomas and Hyperplastic Polyps CLINICS IN COLON AND RECTAL SURGERY/VOLUME 21, NUMBER Polyp Size Location Dysplasia Malignant Mutation Potential Hyperplastic polyp 5 mmProximalYes Yes KRAS Traditional serrated >5 mm Distal Yes Yes KRAS Sessile serrated >5 mm Proximal No Yes BRAF BRAF, v-raf murine sarcoma viral oncogene homolog B1; KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. Endoscopic characteristics of serrated polyps/adenoma of the colonorectum Hyperplastic polypEndoscopic characteristicsManagement of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s favor a small (< 3 to 5 mm) sessile lesion that is pale, often multiple, and located predominantly in the left colon at the rectosigmoid area, usually in older patients.1 It is the most common polyp encountered on flexible sigmoidoscopy. Figure1 Linear and regularly patterned colonic mucosa surrounding a polyp. On endoscopic removal, pathology revealed a hyperplastic colon polyp. A: Before spraying with acetic acid a sessile polyp is seen; B: After spraying with acetic acid the colonic mucosa surrounding the polyp has a linear and regular pattern World J Gastroenterol March 28; 14(12): Figure 2 Nodular and irregularly patterned colonic mucosa surrounding a polyp. On endoscopic removal, pathology revealed a hyperplastic colon polyp. A: Before spraying with acetic acid a sessile polyp is seen; B: After spraying with acetic acid the colonic mucosa surrounding the polyp has a nodular and irregular pattern.World J Gastroenterol March 28; 14(12): Rectal hyperplastic polyps without any clinical significance Gastrointestinal HD Endoscopy Images: Rectal Diseases Endoscopic appearance of SSAManagement of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s is typically a pale, large, sessile lesion that rests on the crest of the mucosal folds. A SSA is predominantly found in the proximal colon of middle-aged women and grows to larger sizes than other serrated adenomas. SSA/P resection also poses challenges
Identification and Resection of Sessile Serrated Adenomas/Polyps during Routine Colonoscopy 2013 Elsevier GmbH. Sessile serrated colon polyps (SSA/Ps) are precursors to colorectal cancer. In comparison to adenomatous polyps, SSA/P can be challenging to detect during colonoscopy; they are often minimally elevated, pale, and concealed behind mucus, a colonic fold, or intraluminal debris. Because they are typically flat, located in the right side of the colon, the same color as the background mucosa, and have indistinct borders, SSA/P resection also poses challenges BURKE, Carol. The clinical importance of serrated lesions of the colorectum. Rev. gastroenterol. Per [online]. 2013, vol.33, n.2, pp ISSN Photo of of flat serrated polyp ( Dr. Wong Kee Song, Mayo Clinic) eFigure 15112. Small Flat Polyp: During screening colonoscopy, a small (6 mm) flat polyp was seen, the outlines of which are well demonstrated by application of a dye (indigo carmine). Histopathology confirmed a sessile serrated adenoma.(Used with permission from Kenneth McQuaid, MD.) CURRENT Medical Diagnosis & Treatment 2014 > Chapter 15. Gastrointestinal Disorders The endoscopic appearance of an SSP is subtle
The endoscopic appearance of an SSP is subtle. The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 They are often the same color as the surrounding mucosa, can be covered with a layer of mucus and have a tendency to look like a prominent fold. One study assessing 7 endoscopic features of SSP found that nearly 50% of SSP express a mean of 2.4 features (20). The prevalence of the characteristic features in the study included a mucus cap (64%), a rim of debris or bubbles (52%), a nodular surface or abnormal fold contour (30-37%), and obscuration of surface blood vessels (32%) (Figura 3). SSPs are usually bigger than adenomas and multiple studies confirm that 50% are > 10 mm Cecum, 1.1 x 0.7 x 0.3 cm.--- Sessile serrated adenoma/polyp with low grade dysplasia VGHKS Traditional serrated adenoma Gross appearance Management of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s favors a pedunculated lesion on the left side of the colon that is easily identified on colonoscopy. Variations in gross appearance may overlap with those of adenomatous polyps Traditional serrated adenoma Traditional serrated adenoma appendix VGHKS Traditional serrated adenomaThe clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Less is known of the rare lesion, the TSA, which is usually left sided, more polyploidy in appearance and comprises < 0.5% of all polyps. Mixed polyp Management of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s These polyps tend to occur in the right side of the colon, are smaller in size, and show a predominance of BRAF mutation with MSI-H and CIMP-H profile. Endoscopic discriminationManagement of Serrated Adenomas and Hyperplastic Polyps Clin Colon Rectal Surg. Nov 2008; 21(4): 273279. doi: /s Endoscopic discrimination between nondysplastic HP and SSA versus dysplastic SSA, TSA, and mixed polyp may be improved using adjuncts to visualization of pit and capillary pattern differences. High-definition colonoscopy with the use of indigo carmine and narrow band imaging can help differentiate between the starlike pit pattern and honeycomb capillary pattern of HP versus the irregularly organized pits and elongated and dilated capillary pattern seen in adenoma. pit pattern of SSAs Editorial: sessile serrated adenomas and their pit patterns: we must first see the forest through the trees. Burke CA1, Snover DC. Am J Gastroenterol Mar;107(3): doi: /ajg A novel pit pattern, Type II-O, has been demonstrated to have a high specificity for SSAs. Unfortunately, the sensitivity is too low to utilize a Type II-O pit pattern to determine which serrated lesion is neoplastic and needs resection. Moreover, there is significant endoscopist-related variability in the detection of serrated lesions of the colon. Efforts to improve the detection of serrated neoplasms are warranted. pit pattern of SSAs A Novel Pit Pattern Identifies the Precursor of Colorectal Cancer Derived From Sessile Serrated Adenoma Am J Gastroenterol.2012;107(3): Through retrospective analysis of a training set (n=145), we identified a novel surface microstructure, the Type II open-shape pit pattern (Type II-O), which was specific to SSAs with BRAF mutation and CIMP. Subsequent prospective analysis of an independent validation set (n=116) confirmed that the Type II-O pattern is highly predictive of SSAs (sensitivity, 65.5%; specificity, 97.3%). A small flat hyperplastic polyp as seen after spraying with indigo carmine SESSILE SERRATED ADNOMA Sessile serrated adenoma/polypSSA/P NBI Sessile serrated adenoma/polypSSA/P Indigocarmine Identification of the Type II open-shape (Type II-O) pit pattern in sessile serrated adenomas (SSAs). (a) Colonoscopic view of a representative SSA with (right) and without indigo carmine dye (left). (b) Magnified views of the SSA areas indicated by the red and yellow boxes in panel a. Left panel: the majority of the pits are Type II-O. Right panel: the upper region is covered by Type II-O pits, whereas the lower region is covered by conventional Type II pits. Schematic diagrams of Type II and Type II-O pits are shown below. (c) Histological appearance of the SSA with Type II-O pits.Am J Gastroenterol.2012;107(3): Tomoaki Kimura MD etc. progression of sessile serrated adenomas (SSAs) with Type II open-shape (Type II-O pits). (a) Schematic diagram of serrated lesions with mixed pit patterns.Am J Gastroenterol.2012;107(3): Tomoaki Kimura MD etc. Traditional serrated adenoma, NBI Therefore, the diagnosis of SSA/P is suggested to be performed using a combination of endoscopic diagnosis, as well as the assessment of tumor location and endoscopic morphology Management of Serrated AdenomaCLINICS IN COLON AND RECTAL SURGERY/VOLUME 21, NUMBER 4 2008
A similar way to patients with conventional adenomas: lack of evidence-based data the natural history of serrated adenoma is not well defined. the recurrence rate and rate of progression to carcinoma remain unknown it is clear that serrated adenomas are a precursor to adenocarcinoma of the colon and rectum. TREATMENT OF S.S.A. From Wikipedia, the free encyclopedia
Complete removal of a SSA is considered curative. Several SSAs confer a higher risk of subsequently finding colorectal cancer and warrant more frequent surveillance. The surveillance guidelines are the same as for other colonic adenomas. The surveillance interval is dependent on (1) the number of adenomas, (2) the size of the adenomas, and (3) the presence of high-grade microscopic features.[5] Recommendations for Treatment Am J Clin Pathol 2005;124:380-391
The interval from diagnosis of SSA to diagnosis of carcinoma was greater than 3 years in 90% of cases and greater than 5 years in 55%. Given these facts and uncertainties, we recommend the following management: Right-sided SSAs without cytologic dysplasia (adenomatous change): RESECTABLE: ENDOSCOPIC REMOVE. NOT COMPLETELY RESECTABLE AND CYTOLOGIC DYAPLASIA: SURGICAL EXCISION, Left-sided lesions OF SSA
Left-sided lesions OF SSA. Recommendations for Treatment Am J Clin Pathol 2005;124: 1. are more problematic. 2. most left-sided SSAs are small lesions and generally are removed at biopsy. 3. For lesions that are not completely excised, repeated endoscopy and complete excision would b recommended. It would be hard to recommend left-sided colectomy or an abdominoperineal resection for such a SSA, even if it could not be resected totally, Recommendations for Treatment Am J Clin Pathol 2005;124:380-391
It is unclear: 1. how rapidly SSA may progress to cancer and 2.what the recurrence rate of SSA is if incompletely resected. These are factors vital to determining 1. the appropriate treatment for unresectable lesions and 2.the appropriate rescreening interval for individuals who have had one or more of these lesions completely removed. Unfortunately, hard follow-up data are lacking The interval to repeated endoscopy Recommendations for Treatment Am J Clin Pathol 2005;124:380-391 The clinical importance of serrated lesions of the colorectum Rev
The clinical importance of serrated lesions of the colorectum Rev. gastroenterol. Perv.33n.2Limaabr./jun.2013 Identification and Resection of Sessile Serrated Adenomas/Polyps during Routine ColonoscopyVideo Journal and Encyclopedia of GI Endoscopy Volume 1, Issue 2, October 2013, Pages 372374 DOI: /S (13)70164-X Retrospective Prospective Or both Quality Measures for Colonoscopy Philip Schoenfeld, MD March 16, 2012 Note: The recommendations assume that the baseline colonoscopy was complete and adequate and that all visible Baseline Colonoscopy: Most Advanced Finding(s) Recommended Surveillance Interval (years) Quality of Evidence Supporting the Recommendation New Evidence Stronger than 2006 No polyps 10 Moderate Yes Small (