Gastroenterology Research and Practice
Volume 2019 (2019), Article ID 1592306, 9 pages
https://doi.org/10.1155/2019/1592306

Research Article

Colorectal Serrated Neoplasia: An Institutional 12-Year Review Highlights the Impact of a Screening Programme

A. J. McCarthy,¹ S. M. O’Reilly,² J. Shanley,¹ R. Geraghty,¹ E. J. Ryan,2,3 G. Cullen,2,3 and K. Sheahan1,3

¹Department of Histopathology, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland
²Centre for Colorectal Disease, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland
³School of Medicine, University College Dublin, Belfield, Dublin, Ireland

Correspondence should be addressed to A. J. McCarthy; aoifejmccarthy@hotmail.com

Received 27 September 2018; Revised 17 December 2018; Accepted 6 January 2019; Published 6 February 2019

Academic Editor: Naohisa Yoshida

Copyright © 2019 A. J. McCarthy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Background. As the malignant potential of sessile serrated lesions/polyps (SSL/Ps) and traditional serrated adenomas (TSAs) has been clearly demonstrated, it is important that serrated polyps are identified and correctly classified histologically. Aim. Our aim was to characterize the clinicopathological features of a series of SSL/Ps & TSAs, to assess the accuracy of the pathological diagnosis, the incidence, and the rate of dysplasia in SSL/Ps & TSAs. Methods. We identified all colorectal serrated polyps between 01/01/2004 and 31/05/2016, by searching the laboratory information system for all cases assigned a “serrated adenoma” SNOMED code. All available and suitable slides were reviewed by one pathologist, who was blinded to the original diagnosis and the site of the polyp. Subsequently discordant cases, SSL/Ps with dysplasia, and all TSAs were reviewed by a second pathologist. Results. Over a 149-month period, 759 “serrated adenoma” polyps were identified, with 664 (from 523 patients) available for review. 41.1% were reviewed by both pathologists; 15.1% (100/664) were reclassified, with the majority being changed from SSL/P to hyperplastic polyp (HYP) (66/664; 9.9%). 80.3% of these HYPs were located in the left colon, and the majority exhibited prolapse effect. There were 520 SSL/Ps (92.2%) & 40 TSAs (7.1%). The majority of SSL/Ps were in the right colon (86.7%) and were small (64.5% <1 cm), while most TSAs were in the left colon (85.7%) and were large (). 6.7% of SSL/Ps exhibited dysplasia, the majority of which were large (). Following consensus review, 13/520 (2.5%) SSL/Ps were downgraded from SSL/P with dysplasia to SSL/P without dysplasia. Detection of SSL/Ps peaked in the most recent years reviewed (87.5% reported between 2013 and 2016, inclusive), coinciding with the introduction of “BowelScreen” (the Irish FIT-based colorectal cancer screening programme). Conclusions. Awareness of, and adherence to, diagnostic criteria is essential for accurate classification of colorectal polyps.

1. Introduction

According to the World Health Organization (WHO), colorectal serrated lesions are a heterogeneous group of lesions characterized morphologically by a serrated architecture of the crypts, and classified histologically as hyperplastic polyps (HYPs), sessile serrated lesions/polyps (SSL/Ps) (with or without cytological dysplasia), or traditional serrated adenomas (TSAs). The features of serrated polyps of the colorectum have been discussed in comprehensive reviews, such as that by Rex et al. [1] and East and colleagues [2]. HYPs, SSL/Ps, and TSAs account for 83%-96%, 3-11%, and 1-7% of all serrated lesions, respectively [2–4]. Approximately 20-30% of all colorectal carcinomas have serrated polyps as their precursor lesion [5–7]. SSL/Ps progress to carcinoma via an intermediate step of SSL/P with dysplasia. These SSL/Ps with dysplasia are advanced lesions with a high risk of rapid progression to malignancy, and thus, it is vital that they are correctly identified by pathologists [8, 9].

The distinction between HYP and SSL/P can be difficult histologically, particularly in the rectum, due to the range of normal histological appearances in the rectum including some bifurcated and dilated crypts and a higher ratio of goblet cells to absorptive cells compared with other areas of the colon [10]. The architecture of rectal crypts is often distorted due to mucosal prolapse [11]. HYPs with mucosal prolapse changes (“HYPs with prolapse effect”) have been defined morphologically as hyperplastic crypts in a background of prolapsed rectal mucosa, characterized by smooth muscle proliferation in the lamina propria with entrapment and distortion of crypts [10].

Carcinomas of the serrated pathway are over-represented in studies of interval colorectal carcinomas [12], occurring due to a range of factors, including endoscopically missed precursor lesions, incompletely resected lesions, rapid progression of de novo lesions, and inadequate surveillance due to pathological misdiagnosis [13–15]. Therefore, efforts to improve pathological diagnosis of serrated polyps should help lead to a reduction in interval colorectal carcinomas [15].

With this in mind, our aim was to retrospectively review a series of serrated colorectal polyps from our institution, focusing on assessing the accuracy of pathological classification, and establishing the clinicopathological features of SSL/Ps and TSAs in our institution.

2. Materials and Methods

2.1. Case Selection

A search was performed using the laboratory information system (LIS) to identify all colorectal polyps assigned a “serrated adenoma” SNOMED code between January 1st 2004 and May 31st 2016. In our institution, the “serrated adenoma” SNOMED code is assigned to all SSL/Ps and TSAs (HYPs have a separate SNOMED code and were not included). Institutional ethical approval was granted.

2.2. Histological Review

All available and suitable haematoxylin and eosin- (H&E-) stained slides were reviewed by one pathologist (AMC), who was blinded to the original diagnosis and to the site in the colon of the polyp. All polyps were evaluated histologically and a diagnosis rendered as follows: HYP, SSL/P (with or without cytological dysplasia), TSA (with or without cytological dysplasia), or other.

2.2.1. Definition of SSL/P

In the United Kingdom, the Pathology sections of the British Society of Gastroenterology (BSG) and National Health Service (NHS) Bowel Cancer Screening Programme have approved the terminology developed by Bateman and Shepherd, namely, sessile serrated lesion (SSL), with or without dysplasia [2, 16], in contrast to the WHO, which utilises the term sessile serrated adenoma/polyp (SSA/P) [17]. In our institution, we use the terminology “sessile serrated lesion/polyp” (“SSL/P”), with or without dysplasia, as agreed with our clinicians (this terminology will be used in the remainder of this paper). In 2012, an Expert Panel stated that “the presence of at least one unequivocal architecturally distorted, dilated, and/or horizontally branched crypt, particularly if it is associated with inverted maturation, is sufficient for a diagnosis of SSL/P” [1], and this is the definition that we used in daily practice in our institution and that we applied in our study.

2.2.2. Definition of TSA

TSAs are characterized by a constellation of typical histological features, namely, striking granular eosinophilic cytoplasm, luminal serrations, the presence of ectopic crypt foci (ECF), and elongated, pencillate nuclei with evenly dispersed coarse chromatin and small inconspicuous nucleoli [18]. Some authors believe that a large proportion (the majority) of TSAs are devoid of cytological atypia (i.e., “TSA without dysplasia”), in the form of mitoses, hyperchromatic crowded nuclei displaying pleomorphism, loss of polarity, pseudostratification reaching the luminal aspects of the lining cells, or architectural features of dysplasia (crowding of glands, back-to-back arrangement, or cribriform patterns) [19].

2.2.3. Definitions of Dysplasia

Histologically, SSL/P with dysplasia is identified by an abrupt transition from ordinary SSL/P to overt dysplasia. The 2010 WHO classification distinguishes two dysplasia patterns, namely, dysplasia resembling that of conventional adenomas and serrated dysplasia [17]. Recently, Liu and colleagues described in detail the morphological features of both conventional and serrated dysplasia in SSL/Ps [15].

The main characteristics of conventional adenomatous dysplasia are the predominant location of the dysplastic component on the surface (i.e., “top–down” dysplasia), with preserved non-dysplastic SSL/P at the base of the lesion and complete similarity to the dysplasia of conventional adenomas. There is no serration, and the lesional dysplastic cells are columnar with at least focal goblet cell differentiation, elongated nuclei, and pseudostratification [15].

An eosinophilic appearance at low power with tightly packed crypts is characteristic of serrated dysplasia [15]. Closely packed, small glands that occupy the full thickness of the mucosa, with occasional cribriform growth, are characteristically present. Architectural serration is less prominent, and the lesional dysplastic cells are cuboidal to low columnar with evident dysplasia, containing round vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Mitoses are frequent, extend to the luminal surface, and can be atypical [15].

Similar to SSL/Ps, two forms of dysplasia are associated with TSAs: conventional dysplasia and serrated dysplasia (defined previously) [18, 20, 21]. Thus, we classified SSL/Ps and TSAs with dysplasia as having “conventional,” “serrated,” or “mixed conventional and serrated” dysplasia (with overlapping features of both types of dysplasia).

As per the WHO, the grade of dysplasia is reported according to a 2-tier system, either low-grade dysplasia or high-grade dysplasia. Low-grade dysplasia is an unequivocal intraepithelial neoplastic condition that must be distinguished from inflammatory or regenerative changes. It is characterized by crowded crypts arranged in parallel, without complexity, back-to-back formation, cribriforming, or budding tubules. The nuclei retain basal orientation, being confined to the bottom half of the cells. Atypical mitoses, loss of polarity, or pleomorphism is not present. The morphological criteria for high-grade dysplasia can be divided into architectural and cytological atypia, with the diagnosis being based on architecture, supplemented by an appropriate cytology. The structural features of high-grade dysplasia are characterized by complex glandular crowding and irregularity, with back-to-back glands. The lesional cells in high-grade dysplasia display loss of cell polarity or nuclear stratification and have markedly enlarged nuclei, with vesicular chromatin and prominent nucleoli. Atypical mitoses are often seen, and prominent apoptosis is frequently present.

2.2.4. Definition of Discordance

Cases that had an alternative diagnosis made following this review to that made by the reporting pathologist were categorised as “discordant cases.” All discordant cases, all SSL/Ps with dysplasia, and all TSAs were reviewed by a second specialized gastrointestinal pathologist (KS), who was blinded to the original diagnosis, to the site in the colon of the polyp and to the opinion of AMC.

2.3. Data Collection

Pathology reports were reviewed, and various demographics were extracted (e.g., patient age and gender, site, and microscopic size of polyps). Anatomic sites were based on the original specimen requisitions submitted by endoscopists, with right-sided colonic polyps being defined as those present in the caecum, ascending colon, hepatic flexure and transverse colon, and left-sided colonic polyps being regarded as those found in, and distal to, the splenic flexure (descending colon, sigmoid colon, and rectum). Specimens that were labelled by the clinician as “random colon” and specimens without any specific designation were all categorised as “colon NOS (not otherwise specified).”

2.4. Data Analysis

Data was recorded and analysed using Microsoft Excel for Mac 2011 Version 14.6.4.

3. Results

3.1. Clinical Data

Over a 149-month period, 759 polyps were assigned a “serrated adenoma” SNOMED code. The H&E-stained slides of 664 of these polyps (from 523 patients) were available for review (endoscopic biopsy: 375; polypectomy: 255; endoscopic mucosal resection (EMR): 19; resection NOS: 11; piecemeal excision: 4). These polyps were from 267 male patients (51.1%) and 256 female patients (48.9%), with a median age of 64 years (range, 19-92 years) (Table 1).

Table 1: Demographics of patients included in this study (664 polyps from 523 patients), all of whom had at least one polyp originally reported as either SSL/P or TSA.

Gender
(%)
Male
267 (51.1%)

Female
256 (48.9%)

Age (years)
Median
64

Range
19–92

Abbreviations: SSL/P: sessile serrated lesion/polyp; TSA: traditional serrated adenoma.

3.2. Histological Analysis

All polyps had been reported by 9 general histopathologists; the workload of all of these pathologists comprised a large proportion of gastrointestinal biopsies.

All polyps included in this study were reviewed by one pathologist (AMC), and 41.1% of polyps (273/664) were reviewed by both pathologists (AMC & KS), with a consensus diagnosis assigned.

15.1% (100/664) of all polyps were reclassified, with the majority reclassified from SSL/P to HYP (66/664; 9.9%) (Table 2). 80.3% of these HYPs were located in the left side of the colon (53/66), and many of these exhibited prolapse effect (16/66) (Figure 1).

Table 2: Reclassification of serrated polyps (SSL/Ps and TSAs) following consensus review by two pathologists; (out of 664 reviewed).

Change in classification
Number (%)

Changed from SSL/P to HYP
66 (9.9%)

Changed from SSL/P to adenoma
7 (1.1%)

Changed from SSL/P to benign polyp NOS
1 (0.2%)

Changed from mixed serrated polyp to adenoma
5 (0.8%)

Changed from TSA to adenoma
21 (3.2%)

Abbreviations: SSL/P(s): sessile serrated lesion(s)/polyp(s); TSA(s): traditional serrated adenoma(s); HYP: hyperplastic polyp; NOS: not otherwise specified.

(a)

(b)

(c)

(d)

Figure 1: Hyperplastic polyp, with prolapse effect, characterized by dilated and congested submucosal blood vessels, thickening of the muscularis mucosae, and upward extension from the hypertrophic and splayed muscularis mucosae, with dilated crypts (a, b). Horizontal extension of crypt bases along the muscularis mucosae can be seen, mimicking the architecturally distorted, dilated, and/or horizontally branched crypts of SSL/Ps (c, d).

21 polyps (3.2%) were reclassified from TSA to conventional adenoma, and 7 polyps (1.1%) were ascribed a diagnosis of adenoma in lieu of SSL/P.

Following review of all 664 polyps by one or both pathologists, there were 520 SSL/Ps (78.3%, 520/664) (Figure 2(a)) & 40 TSAs (6%, 40/664) (Figure 2(d)).

(a)

(b)

(c)

(d)

(e)

(f)

Figure 2: Sessile serrated lesion/polyp (SSL/P) without dysplasia (a). SSL/P with low-grade conventional adenomatous dysplasia (b). SSL/P with low-grade serrated dysplasia (c). Traditional serrated adenoma (TSA) without dysplasia (d). TSA with low-grade conventional adenomatous dysplasia (e). TSA with serrated dysplasia (f).

86.7% of SSL/Ps were located in the right side of the colon (Table 3), with the majority being found in the ascending colon (200/520; 38.5%). 64.5% were small in size (<1 cm), with a mean size of 8.1 mm (median, 8.1 mm; range, 1–32 mm).

Table 3: Characteristics of SSL/Ps identified over a 12-year period at our institution; .

Parameter
All SSL/Ps
SSL/Ps without dysplasia
SSL/Ps with dysplasia (all LGD)

Number (, %)
520
485 (93.3%)
35 (6.7%)

Age of patient (years)

    Median
63
63
69

    Range
19-84
19-84
47-83

Site (, %)

    Right colon
451 (86.7%)
423 (87.2%)
28 (80%)

    Left colon
62 (11.9%)
55 (11.3%)
7 (20%)

    Colon NOS
7 (1.4%)
7 (1.4%)
—

Size (mm)

    Median
8
8
10

    Range
1-32
1-32
3-30

Size category (, %)

    < 1 cm
167 (64.5%)
162 (66.4%)
5 (33.3%)

    ≥1 cm
92 (35.5%)
82 (33.6%)
10 (66.7%)

Abbreviations: SSL/Ps: sessile serrated lesions/polyps; NOS: not otherwise specified; LGD: low-grade dysplasia.

Following consensus review, 13/520 (2.5%) SSL/Ps were downgraded from SSL/P with dysplasia to SSL/P without dysplasia. Overall, 6.7% of SSL/Ps exhibited dysplasia (35/520), all demonstrating low-grade dysplasia. The majority of these were found in the right side of the colon (28/35; 80%), with most being located in the transverse colon (9/35; 25.7%). SSL/Ps with dysplasia (66.7%) were mainly large in size (≥1 cm), with a mean size of 11.3 mm (range, 3–30 mm) (Table 3).

The majority of SSL/Ps exhibited conventional adenomatous dysplasia (25/35; 71.4%) (Figure 2(b), representative image), 3 cases (8.6%) demonstrated serrated dysplasia (Figure 2(c), representative image), and 20% (7/35) displayed a mixture of both conventional and serrated dysplasia.

Detection of SSL/Ps peaked in the most recent years reviewed (87.5% reported between 2013 and 2016, inclusive), coinciding with the introduction of “BowelScreen” (the Irish colorectal cancer screening programme, http://www.bowelscreen.ie) (Figure 3).

Figure 3: The number of SSL/Ps detected between January 1st 2004 and May 31st 2016, with detection of SSL/Ps peaking in the most recent years included in this review (87.5% reported between 2013 & 2016, inclusive). This coincided with the introduction of “BowelScreen” (the Irish colorectal cancer screening programme).

85.7% of TSAs were located in the left side of the colon, with the majority being found in the rectum or sigmoid colon (32/40; 80%). 73.1% were large in size (≥1 cm), with a mean size of 18.6 mm (range, 2–60 mm) (Table 4). 67.5% of TSAs exhibited dysplasia (27/40), with low-grade dysplasia in 60% (24/27 TSAs with dysplasia) and high-grade dysplasia in 7.5% (3/27 TSAs with dysplasia) of all TSAs. The majority of TSAs exhibited conventional adenomatous dysplasia (26/27; 96.3%) (Figure 2(e), representative image), and 1 case (3.7%) demonstrated serrated dysplasia (Figure 2(f), representative image).

Table 4: Characteristics of TSAs identified over a 12-year period at our institution; .

Parameter
All TSAs
TSAs without dysplasia
TSAs with dysplasia

Number (, %)
40
13 (32.5%)
27 (67.5%)

Age of patient (years)

    Median
67
61
68

    Range
34-92
34-86
44-92

Site (, %)

    Right colon
4 (10%)
2 (15.4%)
2 (7.4%)

    Left colon
34 (85%)
9 (69.2%)
25 (92.6%)

    Colon NOS
2 (5%)
2 (15.4%)
—

Size (mm)

    Median
13
10
23.2

    Range
2-60
2-20
4-60

Size category (, %)

    <1 cm
7 (26.9%)
4 (44.4%)
3 (17.6%)

    ≥1 cm
19 (73.1%)
5 (55.6%)
14 (82.4%)

Dysplasia grade (, %)

    Low
24 (60%)
N/A
24 (88.9%)

    High
3 (7.5%)
N/A
3 (11.1%)

Type of dysplasia (, %)

    Conventional
26 (65%)
N/A
26 (96.3%)

    Serrated
1 (2.5%)
N/A
1 (3.7%)

Abbreviations: TSAs: traditional serrated adenomas; NOS: not otherwise specified; N/A: not applicable.

Table 5 highlights the key features of SSL/Ps and TSAs.

Table 5: Characteristics of SSL/Ps & TSAs identified over a 12-year period at our institution.

Parameter
All SSL/Ps
All TSAs

Number (, %)
520
40

Age of patient (years)

    Median
63
67

    Range
19-84
34-92

Site (, %)

    Right colon
451 (86.7%)
4 (10%)

    Left colon
62 (11.9%)
34 (85%)

    Colon NOS
7 (1.4%)
2 (5%)

Size (mm)

    Median
8
13

    Range
1-32
2-60

Size category (, %)

    <1 cm
167 (64.5%)
7 (26.9%)

    ≥1 cm
92 (35.5%)
19 (73.1%)

Dysplasia (, %)

    Low
35 (6.7%)
24 (60%)

    High
—
3 (7.5%)

Type of dysplasia (, %)

    Conventional
25 (71.4%)
26 (65%)

    Serrated
3 (8.6%)
1 (2.5%)

    Mixed
7 (20%)
—

Abbreviations: SSL/Ps: sessile serrated lesions/polyps; TSAs: traditional serrated adenomas; NOS: not otherwise specified.

4. Discussion

We reviewed a large series of serrated polyps over a 12-year period, focusing on the histological diagnosis of SSL/Ps and TSAs, with and without dysplasia. Detection of SSL/Ps peaked in the most recent years included in this review (87.5% reported between 2013 & 2016, inclusive). This coincided with the introduction of “BowelScreen” (the FIT-based Irish colorectal cancer screening programme) and improved recognition of this entity by histopathologists. Similarly, Chetty and colleagues documented increasing awareness in their institution of SSL/Ps as an entity over a 4-year period [22]. With the continued rollout of “BowelScreen” across Ireland, and similar colorectal cancer screening programmes in many other countries, in conjunction with improved colonoscopy techniques, pathologists who report specimens resulting from screening programmes can anticipate encountering SSL/Ps on a regular basis.

Furthermore, this study clearly shows how challenging it can be to distinguish SSL/Ps from HYPs, as there are often only subtle differences, with 66/664 polyps in our cohort (9.9%) being reclassified from SSL/P without dysplasia to HYP following consensus review. In a related study, Gill and colleagues reviewed a large series of right-sided lesions originally diagnosed as HYPs and recategorised 30–64% of HYPs over a 4-year period to SSL/Ps, emphasising again how difficult the distinction between HYP and SSL/P can be [23]. Reviewing all right-sided serrated/hyperplastic polyps was not included in our study design, and thus, we have no information on the rate of under-diagnosis of SSL/Ps in our institution.

Identification of architecturally distorted, dilated, and/or horizontally branched crypts (“L,” “boot,” or “anchor”-shaped crypts), in association with excessive/hyper-serration in the basal half of crypts, is required for a diagnosis of SSL/P (Table 6). However, there are differences of opinion between pathologists in the United States, the United Kingdom, and other parts of Europe regarding the pathological features required to make a diagnosis of an SSL/P. An expert panel, including gastroenterologists, scientists, and pathologists, recommended that serrated polyps with as few as one of these SSL/P-type crypts should be diagnosed as an SSL/P [1]. However, the WHO states that a diagnosis of SSL/P should be made when a serrated polyp shows 2 or 3 contiguous SSL/P-type crypts [24]. Kolb et al. found that using the expert panel criteria resulted in improved interobserver agreement and in an approximately 7% increase in the diagnosis of SSL/P when compared with the WHO criteria [25]. Bettington and colleagues analysed 6340 polyps and reported an SSL/P incidence of 12.1% when WHO criteria were applied, versus 14.7% when using the expert panel criteria. They reported that serrated polyps with any SSL/P-like crypts (expert panel criterion) had clinical features more like SSL/Ps than HYPs (more proximal location, larger size, etc.), and they concluded that only 1 abnormal crypt is necessary for the diagnosis of SSL/P, independent of size and location [26]. In our institution, we apply the recommendations of the expert panel consensus document.

Table 6: Histological features of hyperplastic polyps with prolapse, sessile serrated lesions/polyps, and traditional serrated adenomas [1, 11, 18].

HYP with prolapse effect
HYP:
(i) Simple, elongated crypts
(ii) Serrated structure in the upper half of the crypts
(iii) Some proliferation in the basal (non-serrated) part of the crypts
Prolapse:
(i) Thickening of the muscularis mucosae
(ii) Upward extension from the hypertrophic & splayed muscularis mucosae
(iii) Fibromuscular obliteration of the lamina propria, with dilated crypts

SSL/P
(i) At least one unequivocal architecturally distorted, dilated, &/or horizontally branched crypt (“L,” “boot,” or “anchor”-shaped crypt)
(ii) Inverted maturation (excessive/hyper-serration in the basal half of crypts)

TSA
(i) Striking granular eosinophilic cytoplasm
(ii) Luminal serrations
(iii) Ectopic crypt foci
(iv) Elongated, pencillate nuclei with evenly dispersed coarse chromatin & small inconspicuous nucleoli

Abbreviations: HYP: hyperplastic polyp; SSL/P: sessile serrated lesion/polyp; TSA: traditional serrated adenoma.

In contrast to SSL/Ps, HYPs are characterized by simple, elongated crypts with a serrated structure in the upper half of the crypts, with some proliferation in the basal (non-serrated) part of the crypts (Table 6). Particularly challenging is distinguishing SSL/Ps from HYPs with prolapse effect, and this diagnostic conundrum has been previously documented in the literature [10, 11, 27, 28]. Prolapse complicating HYPs can result in horizontal extension of crypt bases along the muscularis mucosae, mimicking the architecturally distorted, dilated, and/or horizontally branched crypts of SSL/Ps. Histologically, prolapse is characterized by thickening of the muscularis mucosae, with upward extension from the hypertrophic and splayed muscularis mucosae and fibromuscular obliteration of the lamina propria, with dilated crypts [11]. Awareness of this pitfall, particularly in the rectum, will enable histopathologists to render the correct diagnosis.

It is known that SSL/Ps with dysplasia are precursors for interval colorectal carcinomas, and that these lesions are rapidly progressive, difficult to detect endoscopically, commonly incompletely resected, and occasionally misdiagnosed histologically [15, 29]. Due to this significant risk, it is thought that some SSL/Ps should be clinically managed in the same fashion as conventional adenomas, with the British Society of Gastroenterology recommending that patients with certain SSL/Ps (those ≥10 mm or serrated lesions harbouring dysplasia, including TSAs) should be offered a one-off colonoscopic surveillance examination at 3 years [2]. However, such a strategy relies on the ability of histopathologists to reproducibly distinguish SSL/Ps from other serrated polyps, especially those without dysplasia, namely, HYPs, to correctly triage patients. In our study, agreement between the reviewing pathologist’s/pathologists’ and the original pathologists’ histological diagnosis was reached for 85% (564/664) of all polyps reviewed. 100/664 (15.1%) serrated polyps originally classified as SSL/Ps were reclassified as HYPs, adenomas, or benign polyps NOS following consensus review. Strict adherence to the morphological features required [16, 30] for a diagnosis of SSL/P should help to reduce interobserver variability between pathologists.

In a review of SSL/Ps from 2139 patients, Lash et al. identified low-grade dysplasia and high-grade dysplasia in 12% and 2.1% of their patients with SSL/Ps, respectively [3]. Yang and colleagues reported 13,072 SSL/Ps, the majority of which (95%) were negative for dysplasia [9]. 4.6% of their SSL/Ps had low-grade cytological dysplasia, and 0.35% had high-grade cytological dysplasia. Similar to Yang et al., a low rate of SSL/Ps with dysplasia (6.7%) is confirmed in our institution, with conventional adenomatous dysplasia, serrated dysplasia, and a mixture of both conventional and serrated dysplasia in 71.4%, 8.6%, and 20% of SSL/Ps with dysplasia, respectively.

The concept of dysplasia in TSAs is controversial. Many pathologists consider TSAs to be inherently dysplastic and routinely report low-grade dysplasia in TSAs mainly based on elongated, pencillate nuclei [19]. Bettington and Chetty, among others, propose that, although the ordinary TSA is undoubtedly neoplastic, it does not have inherent cytological dysplasia, as the eosinophilic cells of an ordinary TSA are not overtly atypical, do not have mitoses, have minimal proliferative activity by Ki-67 staining, and do not show other immunohistochemical changes to suggest dysplasia (i.e., no abnormal staining with β-catenin, p53, and/or p16) [21, 31, 32]. Thus, the major issue for the practicing pathologist is to recognize areas of overt (e.g. adenomatous) dysplasia arising in a TSA and to bring this to the attention of the endoscopist [19]. With this in mind, following consensus review of our TSAs, we report low-grade dysplasia in 60%, and high-grade dysplasia in 7.5% of TSAs included in our series.

There are some limitations to our study. We did not retrieve and review all polyps that were classified as HYPs, to assess how many would be amended to SSL/P on review. We chose not to interrogate this area, as this has been previously studied and published by other authors [33–41]. Instead, we approached this topic from the opposite viewpoint, by reviewing a large series of serrated polyps already classified as SSL/Ps or TSAs, and focusing on the accuracy of the histological diagnoses of SSL/P and TSA in our institution. We were also keen to establish our rate of dysplasia in SSL/Ps and TSAs, to compare it with that quoted in published literature. Although accompanying ancillary molecular testing would likely be illuminating, it was not employed as this is a purely morphological study highlighting the necessity to strictly adherence to robust diagnostic criteria.

5. Conclusion

As the malignant potential of SSL/Ps and TSAs has been clearly established, it is important that serrated polyps are identified and correctly classified histologically. It is therefore essential for all pathologists to strictly adhere to diagnostic criteria and to be aware of pitfalls in diagnosis. In particular, as has been established in the literature, failure to identify serrated polyps with dysplasia may result in inadequate surveillance and thus increases the risk of interval colorectal carcinoma.

Data Availability

All of the data used to support the findings of this study are included within the article.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

D. K. Rex, D. J. Ahnen, J. A. Baron et al., “Serrated lesions of the colorectum: review and recommendations from an expert panel,” The American Journal of Gastroenterology, vol. 107, no. 9, pp. 1315–1329, 2012.

J. E. East, W. S. Atkin, A. C. Bateman et al., “British Society of Gastroenterology position statement on serrated polyps in the colon and rectum,” Gut, vol. 66, no. 7, pp. 1181–1196, 2017.

R. H. Lash, R. M. Genta, and C. M. Schuler, “Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients,” Journal of Clinical Pathology, vol. 63, no. 8, pp. 681–686, 2010.

N. J. Carr, H. Mahajan, K. L. Tan, N. J. Hawkins, and R. L. Ward, “Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma,” Journal of Clinical Pathology, vol. 62, no. 6, pp. 516–518, 2009.

M. J. O'Brien, Q. Zhao, and S. Yang, “Colorectal serrated pathway cancers and precursors,” Histopathology, vol. 66, no. 1, pp. 49–65, 2015.

M. Bettington, N. Walker, A. Clouston, I. Brown, B. Leggett, and V. Whitehall, “The serrated pathway to colorectal carcinoma: current concepts and challenges,” Histopathology, vol. 62, no. 3, pp. 367–386, 2013.

C. Rosty, D. G. Hewett, I. S. Brown, B. A. Leggett, and V. L. J. Whitehall, “Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management,” Journal of Gastroenterology, vol. 48, no. 3, pp. 287–302, 2013.

M. Bettington, N. Walker, C. Rosty et al., “Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma,” Gut, vol. 66, no. 1, pp. 97–106, 2016.

J. F. Yang, S. J. Tang, R. H. Lash, R. Wu, and Q. Yang, “Anatomic distribution of sessile serrated adenoma/polyp with and without cytologic dysplasia,” Archives of Pathology & Laboratory Medicine, vol. 139, no. 3, pp. 388–393, 2015.

C. C. Huang, W. L. Frankel, T. Doukides, X. P. Zhou, W. Zhao, and M. M. Yearsley, “Prolapse-related changes are a confounding factor in misdiagnosis of sessile serrated adenomas in the rectum,” Human Pathology, vol. 44, no. 4, pp. 480–486, 2013.

B. Singh, N. J. M. C. Mortensen, and B. F. Warren, “Histopathological mimicry in mucosal prolapse,” Histopathology, vol. 50, no. 1, pp. 97–102, 2007.

J. E. G. IJspeert, L. Vermeulen, G. A. Meijer, and E. Dekker, “Serrated neoplasia-role in colorectal carcinogenesis and clinical implications,” Nature Reviews. Gastroenterology & Hepatology, vol. 12, no. 7, pp. 401–409, 2015.

K. S. Nanda, N. Tutticci, N. Burgess, R. Sonson, D. McLeod, and M. J. Bourke, “Caught in the act: endoscopic characterization of sessile serrated adenomas with dysplasia,” Gastrointestinal Endoscopy, vol. 79, no. 5, pp. 864–870, 2014.

H. Pohl, A. Srivastava, S. P. Bensen et al., “Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study,” Gastroenterology, vol. 144, no. 1, pp. 74–80.e1, 2013.

C. Liu, N. I. Walker, B. A. Leggett, V. L. J. Whitehall, M. L. Bettington, and C. Rosty, “Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry,” Modern Pathology, vol. 30, no. 12, pp. 1728–1738, 2017.

A. C. Bateman and N. A. Shepherd, “UK guidance for the pathological reporting of serrated lesions of the colorectum,” Journal of Clinical Pathology, vol. 68, no. 8, pp. 585–591, 2015.

D. C. Snover, D. J. Ahnen, R. W. Burt, and R. D. Odze, “Serrated polyps of the colon and rectum and serrated polyposis,” in WHO Classification of Tumours of the Digestive System, F. T. Bosman, F. Carneiro, R. H. Hruban, and N. D. Theise, Eds., pp. 160–165, IARC Press, Lyon, France, 2010.

R. Chetty, “Traditional serrated adenoma (TSA): morphological questions, queries and quandaries,” Journal of Clinical Pathology, vol. 69, no. 1, pp. 6–11, 2015.

M. L. Bettington and R. Chetty, “Traditional serrated adenoma: an update,” Human Pathology, vol. 46, no. 7, pp. 933–938, 2015.

M. J. Kim, E. J. Lee, S. M. Chun et al., “The significance of ectopic crypt formation in the differential diagnosis of colorectal polyps,” Diagnostic Pathology, vol. 9, no. 1, p. 212, 2014.

M. L. Bettington, N. I. Walker, C. Rosty et al., “A clinicopathological and molecular analysis of 200 traditional serrated adenomas,” Modern Pathology, vol. 28, no. 3, pp. 414–427, 2015.

R. Chetty, L. M. Wang, P. Gill, J. E. East, and S. Leedham, “Left-sided sessile serrated polyps/adenomas,” Human Pathology, vol. 44, no. 9, pp. 1959-1960, 2013.

P. Gill, L. M. Wang, A. Bailey, J. E. East, S. Leedham, and R. Chetty, “Reporting trends of right-sided hyperplastic and sessile serrated polyps in a large teaching hospital over a 4-year period (2009-2012),” Journal of Clinical Pathology, vol. 66, no. 8, pp. 655–658, 2013.

F. T. Bosman, F. Carneiro, R. H. Hruban, and N. D. Theise, “International Agency for Research on Cancer,” in WHO Classification of Tumours of the Digestive System, International Agency for Research on Cancer, Lyon, France, 4th edition, 2010.

J. M. Kolb, S. J. Morales, N. A. Rouse et al., “Does better specimen orientation and a simplified grading system promote more reliable histologic interpretation of serrated colon polyps in the community practice setting? Results of a nationwide study,” Journal of Clinical Gastroenterology, vol. 50, no. 3, pp. 233–238, 2016.

M. Bettington, N. Walker, C. Rosty et al., “Critical appraisal of the diagnosis of the sessile serrated adenoma,” The American Journal of Surgical Pathology, vol. 38, no. 2, pp. 158–166, 2014.

J. R. Parfitt and N. A. Shepherd, “Polypoid mucosal prolapse complicating low rectal adenomas: beware the inflammatory cloacogenic polyp!,” Histopathology, vol. 53, no. 1, pp. 91–96, 2008.

E.-Y. K. Choi and H. D. Appelman, “A historical perspective and exposé on serrated polyps of the colorectum,” Archives of Pathology & Laboratory Medicine, vol. 140, no. 10, pp. 1079–1084, 2016.

N. G. Burgess, N. J. Tutticci, M. Pellise, and M. J. Bourke, “Sessile serrated adenomas/polyps with cytologic dysplasia: a triple threat for interval cancer,” Gastrointestinal Endoscopy, vol. 80, no. 2, pp. 307–310, 2014.

J. E. G. IJspeert, A. Madani, L. I. H. Overbeek, E. Dekker, and I. D. Nagtegaal, “Implementation of an e-learning module improves consistency in the histopathological diagnosis of sessile serrated lesions within a nationwide population screening programme,” Histopathology, vol. 70, no. 6, pp. 929–937, 2017.

J. H. Tsai, J. Y. Liau, Y. L. Lin et al., “Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis,” Modern Pathology, vol. 27, no. 10, pp. 1375–1385, 2014.

B. Fu, S. Yachida, R. Morgan, Y. Zhong, E. A. Montgomery, and C. A. Iacobuzio-Donahue, “Clinicopathologic and genetic characterization of traditional serrated adenomas of the colon,” American Journal of Clinical Pathology, vol. 138, no. 3, pp. 356–366, 2012.

Y. Niv, “Changing pathological diagnosis from hyperplastic polyp to sessile serrated adenoma: systematic review and meta-analysis,” European Journal of Gastroenterology & Hepatology, vol. 29, no. 12, pp. 1327–1331, 2017.

D. Sandmeier, W. Seelentag, and H. Bouzourene, “Serrated polyps of the colorectum: is sessile serrated adenoma distinguishable from hyperplastic polyp in a daily practice?” Virchows Archiv, vol. 450, no. 6, pp. 613–618, 2007.

O. Khalid, S. Radaideh, O. W. Cummings, M. J. O’Brien, J. R. Goldblum, and D. K. Rex, “Reinterpretation of histology of proximal colon polyps called hyperplastic in 2001,” World Journal of Gastroenterology, vol. 15, no. 30, pp. 3767–3770, 2009.

J. C. Anderson, M. Lisovsky, M. A. Greene, C. Hagen, and A. Srivastava, “Factors associated with classification of hyperplastic polyps as sessile serrated adenomas/polyps on morphologic review,” Journal of Clinical Gastroenterology, vol. 52, no. 6, pp. 524–529, 2018.

S. W. Kim, J. M. Cha, J. I. Lee et al., “A significant number of sessile serrated adenomas might not be accurately diagnosed in daily practice,” Gut and Liver, vol. 4, no. 4, pp. 498–502, 2010.

H. Singh, D. Bay, S. Ip et al., “Pathological reassessment of hyperplastic colon polyps in a city-wide pathology practice: implications for polyp surveillance recommendations,” Gastrointestinal Endoscopy, vol. 76, no. 5, pp. 1003–1008, 2012.

C. Schramm, M. Kaiser, U. Drebber et al., “Factors associated with reclassification of hyperplastic polyps after pathological reassessment from screening and surveillance colonoscopies,” International Journal of Colorectal Disease, vol. 31, no. 2, pp. 319–325, 2016.

J. Tinmouth, P. Henry, E. Hsieh et al., “Sessile serrated polyps at screening colonoscopy: have they been under diagnosed?” The American Journal of Gastroenterology, vol. 109, no. 11, pp. 1698–1704, 2014.

G. Schachschal, S. Sehner, M. Choschzick et al., “Impact of reassessment of colonic hyperplastic polyps by expert GI pathologists,” International Journal of Colorectal Disease, vol. 31, no. 3, pp. 675–683, 2016.