A Multinational, Internet-Based Assessment of Observer ... · sessile serrated adenoma, sessile serrated polyp, and serrat-ed polyp with abnormal proliferation (SPAP) have been pro-posed.8-10

938 Am J Clin Pathol 2007;127:938-945938 DOI: 10.1309/NXDB6FMTE9X5CD6Y

© American Society for Clinical Pathology

Anatomic Pathology / OBSERVER VARIABILITY IN SERRATED COLORECTAL POLYPS

A Multinational, Internet-Based Assessment of ObserverVariability in the Diagnosis of Serrated Colorectal Polyps

Katharina Glatz, MD,1 Bobbi Pritt, MD,2 Dieter Glatz, PhD,3 Arndt Hartmann, MD,4

Michael J. O’Brien, MD, MPH,5 and Hagen Blaszyk, MD2

Key Words: Serrated polyps; Observer variability; Colon; Internet

DOI: 10.1309/NXDB6FMTE9X5CD6Y

A b s t r a c t

This Internet-based quiz (http://kathrin.unibas.ch/polyp/) tested the diagnostic variability of 168pathologists in the diagnosis of 20 colorectal polyps on3 representative images, including hyperplastic polyps(HPs), traditional serrated adenomas (TSAs), sessileserrated adenomas (SSAs), and tubulovillous adenomas(TVAs). Interobserver variability for each of the 20lesions was significant and was most pronounced forSSAs. Correct answers were independent of theparticipant’s experience with TVAs, HPs, and TSAs.Participants with gastrointestinal subspecialty trainingand those who had read a reference article on serratedpolyps gave a significantly higher percentage of correctanswers for SSAs. The nomenclature used for serratedpolyps was generally inconsistent. Our results suggestsignificant shortcomings in the routine H&E diagnosisof serrated colorectal polyps. A diagnostically unifyingconcept for lesions of the serrated neoplasia pathway,standardization of nomenclature, training ofpathologists, and possibly development of ancillarytechniques are of paramount importance for accuratepatient management.

The adenoma-carcinoma sequence has been widelyaccepted as the evolutionary paradigm for colorectal cancer,recognizing molecular counterparts to a stepwise process.1-3

Recently, it has been found that serrated polyps, whichaccount for approximately 20% of colorectal polyps, maybe the precursors of 15% to 20% of colorectal cancers.4-6 Inthe past, investigators have considered hyperplastic polyps(HPs) to be an incidental finding with no potential for neo-plastic progression.1 However, for a subset of colorectalcancers, a serrated neoplasia precursor pathway is now pro-posed with sessile serrated adenomas (SSAs) and tradition-al serrated adenomas (TSAs) representing the precursorlesions.7,8 The accurate diagnosis of serrated precursorlesions is, therefore, important, and pathologists need toclassify them consistently.9

Recent detailed histologic analysis provided diagnosticcriteria to identify advanced precursor lesions, or atypicalHPs that are distinct from conventional HPs, and the termssessile serrated adenoma, sessile serrated polyp, and serrat-ed polyp with abnormal proliferation (SPAP) have been pro-posed.8-10 Unfortunately, there is no consensus on whichterm to use, which can potentially create confusion amongmany pathologists and clinicians. Sessile serrated adenomaseems to have gained the widest acceptance among USpathologists, and this term is used throughout this study torefer to such lesions.

Morphologically, HPs are characterized by the absenceof dysplasia and presence of a sawtooth or serrated cryptoutline. They usually remain small (<5 mm) and occurmainly in the rectum and lower sigmoid colon.11 SSAresembles HP but is distinguished on the basis of abnormalbasal crypt architecture with branching and crypt bases

Am J Clin Pathol 2007;127:938-945 939939 DOI: 10.1309/NXDB6FMTE9X5CD6Y 939


Anatomic Pathology / ORIGINAL ARTICLE

whose long axis is parallel to the surface; other histologic cri-teria include proliferative activity in the upper crypt, serrationextending into the crypt base, and an increased number ofgoblet cells with “inverted maturation”—normal or dysplas-tic goblet cells in the crypt base. SSAs are characterized bylarger size, more frequent location in the proximal colon, anddemographically, greater predilection for females.

TSA is a homogeneous lesion composed of a uniform-ly serrated and dysplastic epithelium, the dysplasia usual-ly being less pronounced than in a tubular or villous ade-noma, particularly toward the polyp surface.Architecturally, it often has a villous or tubulovillous con-figuration and appears protuberant rather than sessile.8

The morphologic spectrum of serrated adenomas variesfrom clearly adenomatous lesions to polyps that closelyresemble “conventional” HPs. Very little is known abouthow reproducible the light microscopic diagnosis of ser-rated polyps is among pathologists. It is also far from cer-tain that most pathologists consistently distinguish TSAs,SSAs, and HPs; yet the correct diagnosis of colorectal ser-rated polyps is likely to have implications for risk assess-ment and surveillance.12 This study used images of serrat-ed polyps in an Internet-based quiz to test the diagnosticperformance of pathologists fielding multiple internation-al centers. A survey to gain information on diagnosticterms used by participants was included because there iscurrently no uniformly accepted classification scheme forcolorectal serrated polyps.

Materials and Methods

Quiz Cases

The 20 quiz cases included 8 HPs, 4 TSAs, 4 SSAs, and4 tubulovillous adenomas (TVAs). All cases had been part ofa previous study13 that had linked histologic consensus diag-noses and molecular data ❚Table 1❚. The morphologic featuresdefining HPs, TSAs, and SSAs for inclusion in this study werebased on published criteria.8

Quiz

The online multiple-choice questionnaire and an onlineregistration form had been constructed by the questionnairetool FlexiForm (Department of Computer Science, Universityof Basel, Basel, Switzerland). Pathologists worldwide wereinvited to register for the quiz by e-mail, announcements atpathology meetings, and personal communication.

On registration, participants indicated which diagnosticterms they used for colorectal polyps in daily practice ❚Table 2❚

and ❚Table 3❚. Participants whose native language was otherthan English were asked whether and how they translated theterm serrated adenoma. Once enrolled, all participants receivedan e-mail with personalized URL access to the quiz. The quizwas subdivided into 4 sections with 5 cases each and an intro-ductory section with questions concerning basic personal data(eg, country of origin, practice setting, subspecialty training ingastrointestinal [GI] pathology, professional position, and yearsof experience). Participants were able to stop after any section

❚Table 1❚Quiz Cases With Clinical and Molecular Data*

Mutation Methylation

Quiz Case No./Sex/Age (y) Diagnosis Size (cm) Colonic Site BRAF RAS p16 MLH1 MSI-H Correct (%)

1/F/75 TSA 2.5 Descending Yes No No No No 45.82/M/63 HP 0.7 Rectum No Yes No No No 90.53/F/49 TSA 0.7 Rectum No Yes No No No 46.44/F/52 TVA 0.8 Cecum NA NA NA NA NA 96.45/M/68 HP 0.5 Cecum No Yes No No No 81.56/F/75 HP 0.9 Transverse No Yes No No No 75.07/F/71 TVA 0.5 Rectum NA NA NA NA NA 88.18/M/41 SSA 1.0 Transverse Yes No Yes Yes No 53.69/F/42 HP 1.3 Sigmoid No No No No No 61.3

10/M/52 TSA 1.8 Transverse Yes No No Yes No 49.411/F/58 SSA 1.2 Ascending Yes No No Yes No 37.512/M/49 HP 0.5 Rectum No Yes No No No 80.413/M/62 TSA 3.0 Sigmoid No Yes No No No 34.514/M/54 HP 0.6 Ascending Yes No No Yes No 85.115/M/55 SSA 1.5 Cecum Yes No No Yes No 60.116/M/47 TVA 0.6 Ascending NA NA NA NA NA 76.817/F/59 HP 0.8 Sigmoid No Yes No No No 80.418/M/60 SSA 3.0 Transverse No No No Yes No 64.919/F/43 HP 0.8 Transverse No Yes No No No 74.420/M/82 TVA 0.5 Rectum NA NA NA NA NA 98.2

HP, hyperplastic polyp; MSI-H, microsatellite instability, high; NA, not available; SSA, sessile serrated adenoma; TSA, traditional serrated adenoma; TVA, tubular/tubulovillousadenoma.

* Participants knew the clinical information. The last column shows the percentage of correct answers given for each case by all 168 participants.



Glatz et al / OBSERVER VARIABILITY IN SERRATED COLORECTAL POLYPS

and reaccess the quiz later for completion. Three representativeimages (×20, ×100, and ×200) of each H&E-stained polyp wereprovided. Information on patient age and sex, polyp size, andpolyp location was given to simulate everyday pathology prac-tice (Table 1; http://kathrin.unibas.ch/polyp/). Molecular data werenot provided. For each quiz case, participants had to choose from1 of the following 4 diagnostic categories: HP, serrated adenoma,SSA/sessile serrated polyp/SPAP, and tubular/villous/TVA. Thenumber of cases in each diagnostic category was unknown toparticipants. Reading the article by Snover et al8 detailing mor-phologic diagnostic criteria of serrated polyps was recommend-ed before answering the quiz. Participants who completed thequiz within 7 weeks received an e-mail with an attached list ofcorrect answers along with a statement to confirm participation(the equivalent of 2 continuing medical education credits) pro-vided by the Swiss Society of Pathology. All online answerswere exported into an Excel (Microsoft, Redmond, WA) file forstatistical evaluation of the data.

Data Analysis

Contingency table analysis was used to study frequencycomparisons of nominal categorized variables.

Results

Participants

Of the 244 initial registrants, 168 completed the quiz.Most participants (68 women, 100 men) practiced in Germany(n = 58), the United States (n = 39), and Switzerland (n = 34).Geographic areas with fewer participants included Canada

(n = 7), Italy (n = 5), Austria (n = 4), New Zealand (n = 4), andFrance (n = 3). The remaining 14 participants were from 9other countries. There were 106 board-certified pathologists(31 with GI pathology subspecialty training), 28 fellows (9with GI pathology subspecialty training), 29 residents, and 5others (student, scientist, or not further specified). Participantspracticed at academic health centers or universities (n = 90),community hospitals (n = 44), and in privately run laborato-ries with up to 4 pathologists (n = 23) or more than 4 pathol-ogists (n=11). A majority (122) of the participants were boardcertified (21 for <3 years, 44 for up to 10 years, and 57 for >10years), whereas 46 participants were not board certified yet.

Terms Used for Colorectal Polyps

We asked participants in a multiresponse question on reg-istration (n = 244) to indicate which of 19 terms they used intheir daily practice (Table 2). Additional terms used for serratedpolyps were given by 8 registrants: HP with atypical features

❚Table 3❚Preferred Term for Many, Large, or Proximal Polyps by 244Participants*

With GI Without GI Subspecialty Subspecialty

Training (n = 54) Training (n = 190)

Serrated adenomatous polyposis 25.9 12.6Hyperplastic polyposis 44.4 22.1Metaplastic polyposis 0 2.1I have never diagnosed this condition 29.6 63.2

GI, gastrointestinal.* Data are given as percentages.

❚Table 2❚Terms Used in Daily Practice as Indicated by 244 Participants*

With GI Subspecialty Without GI Subspecialty Training (n = 54) Training (n = 190) All

Hyperplastic polypMicrovesicular type 5.6 3.7 4.1Goblet cell–rich type 7.4 4.2 4.9Mucin-poor type 5.6 2.1 2.9

Traditional serrated adenoma 27.8 9.5 13.5 (P < .0001)Serrated adenoma 87.0 81.1 82.4Sessile serrated adenoma 51.9 26.3 32.0 (P < .0001)Sessile serrated polyp

Favor sessile serrated adenoma 16.7 2.6 5.7 (P < .0001)Favor hyperplastic polyp 7.4 4.2 4.9

Serrated polyp 11.1 20.5 18.4Sessile serrated polyp 16.7 8.9 10.7Serrated polyp with abnormal proliferation 3.7 3.7 3.7Serrated adenoma not used 0.0 12.1 9.4 (P = .005)Mixed hyperplastic polyp–serrated adenoma 50.0 33.7 37.3 (P = .029)Mixed traditional serrated adenoma–sessile serrated adenoma 14.8 1.6 4.5 (P < .0001)Mixed sessile serrated adenoma–tubular/villous adenoma 33.3 14.2 18.4 (P = .001)Mixed adenomatous/hyperplastic polyp 63.0 60.0 60.7Mixed polyp 74.1 15.8 28.7

GI, gastrointestinal.* Data are given as percentages.




(3 times), HP with dysmaturational features (1 time), TVA/vil-lous adenoma, serrated type (3 times), and circumscribedhyperplasia of the colonic mucosa (1 time). Three participantsincluded a grading of serrated polyps into low- or high-gradedysplasia. We also asked for the preferred term used for many,large, or proximal serrated polyps (Table 3).

Of 124 German-speaking participants, only 35 translatethe English term serrated adenoma into German; the remain-der provided a total of 24 different translations.

Quiz Results

The original quiz cases and the percentage of answersgiven by the participants can be viewed at http://kathrin.unibas.ch/polyp/.

For each of the 20 quiz cases, the percentage of correctanswers ranged from 34.5% (case 13, SSA) to 98.2% (case 20,TVA). The median percentage of correct answers for the diag-nostic categories TVA (92%), HP (81%), and TSA (48%) wasindependent of participant experience. Comparison of answersfrom pathologists with (n = 39) and without (n = 129) GI sub-specialty training revealed significant differences in the SSAdiagnostic category ❚Figure 1A❚. Pathologists without GI sub-specialty training most often confused SSAs with TSAs or HPs.

The quiz referenced a recent article8 as suggested readingbecause the histologic consensus diagnosis for all 20 lesionswas based on the morphologic description of serrated polypsin this reference. A majority (92) of participants stated thatthey had read the article (62% of all participants with GI sub-specialty training and 53% of all participants without GI sub-specialty training). Analogous to pathologists without GI sub-specialty training, the 76 participants who had not read therecommended article showed a significantly lower perfor-mance for the SSA diagnostic category ❚Figure 1B❚.

Most participants rated the image quality as good(51.2%) or excellent (35.7%), and a minority (11.9%) as mod-erate. Only 1.2% of participants rated image quality as poor.Similar Internet-based pathology quizzes would be appreciat-ed by 92.3% of the participants.

Results for Selected Cases

Some of the 20 quiz cases stood out because they receivedthe correct answer from fewer than 50% of participants. Case11 (SSA) was diagnosed correctly by only 37.5% of patholo-gists, whereas 44.6% diagnosed this case as HP. Case 13❚Image 1❚ was diagnosed correctly as TSA by only 34.5% ofthe participants, whereas 59.9% of pathologists thought thispolyp to be a TVA. Cases 1 and 10 (TSAs) were most oftenmistaken for TVAs, likely as the result of prominent villousarchitecture and low-grade dysplasia ❚Image 2❚. In contrast,case 20 was correctly recognized as TVA by 98.2% of all par-ticipants. Thus, the low diagnostic rate of some cases of TSAand SSA cannot be explained by the general quiz format alone.

Individual Results

No participant achieved the maximum score of 20 pointsfor 20 correct answers. The highest score of 19 points wasobtained by 3 board-certified pathologists and a fellow. Thelatter and 1 of the pathologists had GI subspecialty training. Aresident scored lowest (5 points). The mean ± SD score for allparticipants was 13.8 ± 3.0. Performance was largely unaffect-ed by the practice setting (university, community hospital, pri-vate practice with 1-4 pathologists, or private practice with 5+pathologists). When professional positions were analyzed sep-arately, the 9 fellows with GI subspecialty training performedbest with a mean ± SD score of 16.33 ± 1.93, whereas the 29residents scored lowest (12.41 ± 2.96). Pathologists from the

❚Figure 1❚ The 20 lesions of this survey were classified according to morphologic features described in a recent article.8 A,Comparison of results from pathologists with (n = 39; white bars) and without (n = 129; black bars) GI subspecialty trainingrevealed significant differences in the sessile serrated adenoma (SSA) diagnostic category. B, Similarly, participants who had notread the article8 (n = 76; black bars) showed a significantly lower performance for the SSA diagnostic category than participantswho had read it (n = 92; white bars).

1009080706050403020

HyperplasticPolyp

SerratedAdenoma

SessileSerratedAdenoma

P = .025

Adenoma

100

Co

rrec

t A

nsw

ers

(%) 100

9080706050403020

HyperplasticPolyp

SerratedAdenoma

Co

rrec

t A

nsw

ers

(%)

SessileSerratedAdenoma

P < .0001

Adenoma

100

A B




3 countries with the highest numbers of participants(Germany, 58; United States, 39; and Switzerland, 34) hadmean ± SD scores of 13.45 ± 3.07, 14.18 ± 3.13, and 13.88 ±3.20, respectively.

Discussion

Recent evidence supports an alternative pathway for co-lorectal carcinogenesis through serrated polyps.10,14-17 Theexistence of this serrated neoplasia pathway requires thatpathologists be able to accurately classify precursor lesions ofthis pathway for optimal patient management.

The serrated polyp quiz described herein tested the abili-ty of pathologists to distinguish 2 precursor lesions of thispathway, ie, TSA and SSA, from HP and TVA. The study wasInternet-based to involve as many pathologists from a variety

of countries as possible. The quiz design included 3 represen-tative static images per lesion (×20, ×100, and ×200 magnifi-cation). This format does not reflect routine pathology prac-tice but it compares well with static-imaging telepathologyconsultation for which a high diagnostic accuracy has beenshown.18,19 This design likely represents the single mostimportant source of bias, as indicated by a relatively low per-centage of correct diagnoses for TVA (90%) and HP (80%).Future Internet-based surveys could prevent such bias byusing virtual slides that show the entire lesion rather than rep-resentative static images. The answer key of this Internet quiznow includes 3 representative virtual slides showing charac-teristic features of SSA, TSA, and HP as a teaching tool, butparticipants of the quiz had only 3 static images availablewhile taking the test.

Another source of bias is the nonrandom selection of par-ticipants. All authors sent invitations to participate in the quiz

A B

C ❚Image 1❚ (Case 13) The supplied images led to a diagnosis oftraditional serrated adenoma by only 34.5% of participants,whereas 59.9% of pathologists thought this polyp to be atubular/tubulovillous adenoma. The architecture is partiallypedunculated and villiform with some serrated glands. There is a population of eosinophilic columnar cells extending to thesurface showing nuclear pseudostratification. Significantnuclear hyperchromasia can be seen in some areas. Mitosesare uncommon. Thus, at least portions of this lesion showoverlapping histologic features with tubular/tubulovillousadenoma, which highlights the diagnostic dilemma present insome cases (A, H&E, ×20; B, H&E, ×100; C, H&E, ×400).




by e-mail to their professional contacts who were asked totake the quiz and, in turn, forward the invitation e-mail to theirprofessional contacts. The 244 registrations translated into168 completed surveys. This limited “snowball effect” and a31.1% dropout rate after registration likely reflect a combina-tion of busy schedules and lack of interest and/or motivation.Subsequently, participants likely comprised motivated, curi-ous pathologists with interest in the subject matter and fewpassive-aggressive tendencies. It is debatable whether thediagnostic skills of such self-selected participants are repre-sentative of the entire pathology community.

Correct answers for the diagnostic categories SSA (54%)and TSA (44%) were considerably lower than for the TVA andHP groups. SSAs were most often confused with HPs orTSAs. Diagnostic problems distinguishing SSA from HP andSSA from TSA have been described previously.8,9,20 TSAs canbe misdiagnosed as TVAs if the serrated architecture is lesspronounced and nuclear pseudostratification and hyperchro-masia are prominent. Some of the quiz cases highlight thediagnostic ambiguity that faces pathologists in everyday prac-tice. The histologic features of SSA were less prominent in

case 11 compared with the other 3 SSAs ❚Image 3❚, leading toa misdiagnosis of HP by 44.6% of participants. Case 13showed a KRAS mutation and no evidence of BRAF mutationand low levels of CpG island methylation. This molecular pro-file is more likely to be associated with TVA than TSA.17

Ultimately, the majority of participants (59.9%) had chosenthe most likely correct diagnosis of TVA in this case. Ancillarymarkers that would help in diagnostically challenging cases ofSSA need to be cost-effective and easy to perform in dailypractice, but are not available at this point (MIB-1 and MCM-2 immunohistochemical analysis does not aid in identificationof serrated colorectal polyps with abnormal proliferation21).

Histologic assessment remains the current diagnostic“gold standard” in SSA, and pathologist education is an excel-lent tool for providing clinicians with the best possible diag-noses when encountering serrated colorectal polyps. Threefindings of our study support this view: (1) Participants whoread the reference article8 on serrated polyps performed sig-nificantly better than those who did not. (2) SSAs were cor-rectly diagnosed significantly more often by participants withGI subspecialty training. (3) The type of practice setting (aca-demic center vs private practice) had no impact on the meanscore of participants. Our findings attest to the large numberof pathologists in private practice who remain diagnosticallyup-to-date without the support network of a large academiccenter. There were no significant differences in the diagnosticperformance of various participant groups in recognizing thewell-defined entities of HP, TVA, and TSA.

Consensus for the nomenclature of serrated polyps ingeneral, and SSA in particular, has not been reached, consis-tent with our survey on the use of terms among the 244 pathol-ogists who initially registered. GI pathologists use the termsTSA and SSA significantly more often than do pathologistswithout GI subspecialty training. It is interesting that 9.4% ofpathologists without subspecialty training admitted to neverusing the term serrated adenoma. Many participants use theterm mixed adenomatous/HP, independent of subspecialtytraining, but terms designating mixtures of various subgroupsof serrated polyps are mostly used by GI pathologists.Alternative names used by some for SSAs include SPAP andsessile serrated polyp. We advocate use of the terms TSA andSSA because they (1) reflect their genetic uniqueness andrelatedness best, (2) are currently used by the majority of GIpathologists, and (3) contain the word adenoma as a flag toclinicians. We also advocate not using the term serrated ade-noma without the preceding qualifiers of traditional or sessile.This approach will greatly aid in using unified terminology forserrated colorectal polyps.

The current lack of consensus on terminology is unfortu-nate because it adds to the uncertainty of clinical manage-ment, especially if a patient moves to a different health systemin which the pathologists prefer an alternative name for SSAs.

❚Image 2❚ (Case 1) This traditional serrated adenoma wasmistaken for a tubular/tubulovillous adenoma by 39.3% ofparticipants. The architecture is mostly pedunculated andvilliform. Patchy serrated glands are evident. There is auniform population of eosinophilic columnar cells extendingto the surface showing mild nuclear pseudostratification andsome hyperchromasia. Mitoses are uncommon. Thedistribution of participants’ answers is likely due to prominentvillous architecture in the supplied images. Numerousintraepithelial lymphocytes may have been mistaken formitotic figures secondary to suboptimal high-power imagequality (not shown) (H&E, ×20).




It is hoped that upcoming review articles and new editions ofGI reference books will succeed in overriding cemented opin-ions on the names of serrated colorectal polyps, in favor ofusing TSA and SSA. One third of German-speaking partici-pants translated serrated adenoma into 24 different Germanterms because there is no authorized German translation forserrated adenoma. Thus, non–English-speaking countries arein even greater need of a unified classification scheme. It islikely that continued progress in understanding the molecularbasis and clinical significance of the serrated polyp neoplasiapathway by researchers, clinicians, and surgical pathologistswill lead to unifying concepts and uniform classification of theserrated neoplasia pathway and histologic categories.

From the Departments of 1Pathology and 3Computer Science,University of Basel, Basel, Switzerland; and Pathology,2University of Vermont College of Medicine, Burlington;4University of Regensburg, Regensburg, Germany; and 5BostonUniversity School of Medicine, Boston, MA.

Address reprint requests to Dr Blaszyk: Dept of Pathology,University of Vermont College of Medicine, 89 Beaumont Ave,Burlington, VT 05405.

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molecular characteristics of hyperplastic polyposis.Gastroenterology. 2000;119:323-332.

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A B

C ❚Image 3❚ (Case 11) The supplied images showed histologicfeatures of sessile serrated adenoma (SSA) that were lessprominent compared with the other 3 SSAs of this survey,leading to a misdiagnosis as hyperplastic polyp by 44.6% ofparticipants. A disorganized serrated architecture is evident insome but not all areas of the polyp. There is only focal cryptdilatation, crypt branching, and early herniation of epitheliuminto the submucosa. Some crypts show serration that startsat or near the base of the crypt. The surface epithelium ismostly bland with some tufting. This lesion shows significantmorphologic overlap with hyperplastic polyp, which isreflected by participants’ answers (A, H&E, ×20; B, H&E,×100; C, H&E, ×400).




5. Huang CS, O’Brien MJ, Yang S, et al. Hyperplastic polyps,serrated adenomas, and the serrated polyp neoplasia pathway.Am J Gastroenterol. 2004;99:2242-2255.

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20. Longacre TA, Fenoglio-Preiser CM. Mixed hyperplasticadenomatous polyps/serrated adenomas: a distinct form ofcolorectal neoplasia. Am J Surg Pathol. 1990;14:524-537.

21. Gray D, Obermann EC, Evans M, et al. MIB-1 and MCM-2immunohistochemical analysis does not aid in identification of serrated colorectal polyps with abnormal proliferation. Am J Clin Pathol. 2006;125:407-412.

Documents

A Multinational, Internet-Based Assessment of Observer ... · sessile serrated adenoma, sessile serrated polyp, and serrat-ed polyp with abnormal proliferation (SPAP) have been pro-posed.8-10