Introduction: Diagnostic and reporting errors are one of the major challenges encountered in provision of quality health care services. Incorrect diagnosis interferes with clinical decision making and ends up with serious consequences in terms of patient management. Practicing regular departmental audits is a milestone towards professional development and excellence. The aim is to highlight and address errors and discrepancies in routine practices to maintain high quality standards and take corrective actions for future. Shaukat Khanum Memorial Cancer hospital being one of the largest cancer centers in Pakistan, colorectal polyps are not an uncommon biopsy specimen received in surgical pathology lab. We conducted an intra-departmental audit of colorectal polyps. The aim of our study was to investigate diagnostic accuracy and quality of reporting of colorectal polyps according to standardized CAP guidelines.

Material and Methods: We performed a retrospective study of 229 cases of colorectal polyps diagnosed in year 2019 after approval by institutional review board. The data was available in hospital archives. Slide review was done by two consultant pathologists to assess diagnostic and reporting errors. The conflicting cases were referred to a third pathologist for final opinion.

Results: The diagnostic discrepancies were observed in 20 (6.1%) cases and reporting errors were present in 61 (18.6%) out of 229 cases (328 biopsies).

Conclusion: Overall the results were satisfactory in terms of patient management. There was only one case with discrepant grading of dysplasia and there were four cases with overcall of adenocarcinoma which turned out be high grade dysplasia on review.

Keywords: Colorectal Cancer (CRC); College of American Pathologists (CAP); Mucin Rich Traditional Serrated Adenomas (MR-TSAs); Serrated Tubulovillous Adenomas (S-TVAs)

Colorectal cancer is the second most common cancer in women and third most common malignancy in males worldwide [1]. The incidence is higher in well developed countries compared to low-income countries. The established risk factors are dietary habits like consumption of alcohol and processed meat, sedentary lifestyle and genetic predisposition. Colorectal polyps are precursor lesions that can harbor genetic rearrangements, develop high grade dysplasia and can undergo malignant transformation. Colorectal screening programs are used worldwide for early detection of precursor lesions and identification of patients at high risk of developing colorectal cancer.

Unfortunately, there is no such screening strategy operating at present in Pakistan and majority of polyps are diagnosed as incidental endoscopic finding. Few cases of larger polyps present with abdominal discomfort, bleeding and diarrhea. The primary objective of our study was to assess diagnostic accuracy of colorectal polyps. Furthermore, we also aimed to investigate quality of reporting of colorectal polyps according to standardized CAP guidelines.

After approval by institutional review board, we retrospectively reviewed 241 consecutive cases of colorectal polyps diagnosed in the year 2019. The data was retrieved through the hospital archives. The small mucosal biopsies diagnosed as colorectal polyp, history of polyposis syndrome or with endoscopic impression of polyp (229 cases) were included in the study. Larger resections including total and hemi-colectomies (12 cases) were excluded from the study. After applying inclusion-exclusion criteria we were left with a total of 229 cases. A double-blind slide review was done by two independent consultant pathologists with significant experience in gastrointestinal pathology to avoid personal bias. Diagnostic accuracy was assessed on the basis of correct categorization of polyps, grading of dysplasia and correct assessment of malignancy arising in a polyp. The cases marked as discrepant by two pathologists were re-discussed on a multi-head session. The cases with difficult assessment and high subjectivity were referred to a third pathologist for final opinion. 

Dysplasia in conventional adenomas was graded according to two-tiered stratification as low and high grade dysplasia based on cytological and architectural changes. However, grading the severity of dysplasia into low or high grade in serrated lesions is not recommended by WHO [1]. The quality of reporting was assessed according to CAP protocol for examination of excisional biopsy (polypectomy) specimen April 2021 [2-4]. The core data items recommended in CAP guidelines were tumor site, tumor size (including polyp size, configuration and size of invasive carcinoma if present), histological type (use of standardized terminologies), grading of dysplasia, extent of local invasion (for malignant polyps), comment on mucosal margin (for sessile polyp), deep margin (for pedunculated polyp with stalk) and lymphovascular invasion.

Results:
Table 1 shows the baseline histomorphological features of 229 cases (328 biopsies) of colorectal polyps. Majority of cases had multiple biopsy specimens from different sites making the total biopsy count as 328. There was male pre-dominance (73.8%). Location wise, left colon harbored maximum number of polyps 184 (56.1%), pre-dominantly in rectum and anal canal 74 (22.6%). There were 107 (31.7%) single polyps ranging in size from 1 - 25 mm. Rest of the polyps were received as multiple mucosal fragments. We broadly classified the data into conventional colorectal adenomas, serrated lesions and polyps, inflammatory polyps, adenocarcinoma (with and without precursor lesion), genetic syndrome associated polyps, mucosal prolapse polyps, no significant pathology and cases signed out as descriptive without histological features of polyp Table 2. Tubular adenomas with low grade dysplasia 72 (18.3%) constituted the largest group.

Table 1: Baseline histopathological features of 229 cases (328 biopsies).

IRB Approval number: EX-04-06-21-03.

Table 2: Original diagnosis and discrepancies in 229 cases (328 biopsies) of colorectal polyps.

The diagnostic discrepancies were observed in 20 cases (6.1%). Errors in correct categorization were present in 15 cases. 6 cases of conventional adenomas had incorrect diagnosis. 2 of these 6 cases were under-diagnosed as non-neoplastic, one case as focal hyperplastic change, juvenile rectal polyp (1 case) and two cases were signed out as focal active colitis. 3 cases of sessile serrated lesions were incorrectly diagnosed as conventional adenomas. Hyperplastic polyp (1 case) was misdiagnosed as tubular adenoma with low grade dysplasia. Prolapse associated polyp (1 case) and 1 case of juvenile rectal polyp were incorrectly categorized as hamartomatous polyp and inflammatory polyp respectively. 3 cases had no adenomatous change and were over-diagnosed as conventional adenomas. Error in grading of dysplasia was observed in 1 case of tubular adenoma with high grade dysplasia which was under-graded as low grade dysplasia. There was overcall of adenocarcinoma in 4 cases which turned out to be conventional adenomas with high grade dysplasia on review.

The reporting discrepancies were observed in 61 cases (18.6%). Major reporting discrepancies encountered during review were use of non-standardized terminologies, inappropriate sub-typing of conventional adenomas, missing comment on size of invasive tumor in a malignant polyp , margin status and lymphovascular invasion. 21 cases were reported as adenomatous polyps which is not a standardized term. Conventional adenomas should ideally be reported as tubular, villous or tubulovillous adenomas. Furthermore 10 cases with colonoscopic impression of polyp were signed out as polypoidal colonic fragments with hyperplastic change which is again not a correct terminology. On review, all 10 cases showed no significant pathology highlighting the bias of the signing out pathologist towards colonoscopic impression of polyp. Problem in correct sub-typing was observed in two cases of conventional adenomas, one having <25% villous architecture and wrongly reported as tubulovillous adenoma and the other having >25% villous architecture and misdiagnosed as tubular adenoma.

Out of 107 intact polyps, there was no comment on margin status (free or involved by dysplasia) in 28 cases of conventional adenomas with low grade dysplasia and 1 with high grade dysplasia. 2 cases had adenocarcinoma arising in a background of tubulovillous adenoma. There was no comment on size of invasive tumor arising in polyp, margin assessment and lymphovascular invasion. Rest of the polyps were received fragmented.

Over the past decade, there has been significant advancement in endoscopic procedures of superficial colorectal lesions. These advanced endoscopic procedures have opened a new era of interdisciplinary collaborative efforts of a pathologist and gastrointestinal endoscopist to understand each other's perspective. These advanced procedures are more targeted and demand more precise, detailed and meticulous pathology reporting to optimize patient management. The quality assurance audit we performed brought into light many diagnostic and reporting errors. Diagnostic difficulty in correct categorization of sessile serrated lesions and conventional adenomas was observed in 3 cases (3.7%). According to WHO 2019 the diagnostic criteria for sessile serrated lesion is “The Presence of Single Unequivocal Architecturally Distorted Crypt”. The architecturally distorted crypt was explained by presence of at least one of these features i.e. Serrations extending to crypt base, horizontal growth along muscularis propria (T or L-shaped crypts) and dilatation of basal third of crypts Figure 1. Three types of dysplasia have been described in serrated lesions with dysplasia by Crockett and Nagtegaal (2019) [5] i.e. Intestinal dysplasia, serrated dysplasia and minimal deviation dysplasia [5]. Intestinal dysplasia is relatively rare and is similar to dysplasia in conventional adenoma. MLH1 satin shows retained expression and very rarely show malignant transformation. Serrated dysplasia is characterized by eosinophilia cytoplasm, closely packed glands, nuclear atypia and mitotic activity. Loss of MLH1 staining is not very common. Minimal deviation dysplasia is similar to sessile serrated lesion with characteristic loss of MLH1 expression.

Figure 1: A) Sessile serratedlesion. Note the serrations extending to the crypt base, basal dilatation and horizontal growth pattern. B) Conventional adenoma.

On the flip side, conventional adenomas are subtyped primarily on the basis of their villosity and graded for dysplasia depending upon the severity of both architectural and cytological abnormalities. Here a question may arise which one is on a faster track of developing colorectal cancer serrated pathway or adenoma - adenocarcinoma sequence? This question was investigated by a number of studies that came up with conflicting results. A study by Lash RH et al [6] published in 2010 suggested that progression of serrated pathway to CRC is slower than adenoma- adenocarcinoma sequence Figure 2. Another more recent study (2021) by Bateman AC et al [3] supported the faster track of serrated pathway compared to conventional adenomas. According to AC Bateman once conventional dysplasia develops in sessile serrated lesions (SSL with dysplasia) the progression to colorectal cancer is faster.

Figure 2: Spectrum of adenoma -adenocarcinoma sequence. A) Villous adenoma, B) Tubular adenoma, C) Tubular adenoma with high grade dysplasia, D) Adenocarcinoma arising in a background of tubulo-villous adenoma.

Inflammatory polyp Vs juvenile rectal polyp was another area of diagnostic challenge. One case (1.2%) of juvenile polyp was mis-diagnosed as inflammatory polyp. Although there is a wide histomorphological overlap between the two entities, one should report them with caution [7] Figure 3. The inflammatory polyps occur secondary to inflammatory bowel disease, ischemic disease, infections (C.difficle, E.coli, Campylobacter), secondary to ulcers and at anastomotic site. A recent study (2020) by Ashktorab H et al [8] showed that inflammatory polyps occur more commonly in inflammatory bowel disease compared to other form of colitis. This study also demonstrated increased frequency of polyps in ulcerative colitis than crohn's disease. >90% of juvenile (retention) polyps occur in childhood in the first ten years with peak age incidence being 2 to 5 years.

Figure 3: A) Inflammatory myoglandular polyp (The arrow head points at proliferating smooth muscle), B) Juvenile Polyp.

Recommendation: In young children with no history of inflammatory bowel disease or other infectious etiology, one should be cautious not to misdiagnose juvenile polyp as inflammatory polyp. False interpretation of juvenile polyps associated with juvenile polyposis syndrome can lead to serious prognostic implications.

According to WHO (2019): Patients diagnosed as juvenile polyposis syndrome of infancy rarely survive 2 years due to complications like diarrhea, severe anemia and hypoalbuminemia[1] . Patients with juvenile polyposis coli/generalized juvenile polyposis syndrome have higher risk of developing colorectal and upper gastrointestinal cancer compared to inflammatory polyps [1] and should be kept on close surveillance. Molecular analysis can further help in correct categorization of the polyps. Atypical Juvenile polyps (Type B epithelial phenotype) harbor SMAD4 and typical juvenile polyps (Type A classic juvenile polyps) show BMPR1A germline mutations. Inflammatory polyps associated with inflammatory bowel disease can develop dysplasia and oncogenic mutations of TP53 and MYC amplification [1].

Grading the severity of dysplasia was one of the diagnostic discrepancies encountered in one case (1.2%) of our study. The main caveats in diagnosing high grade dysplasia were over-reliance on cytological abnormalities alone and overcalling architectural complexity and surface changes.

Recommendation: High dysplasia should be graded by combination of both architectural abnormalities (complex glandular crowding, cribriforming, irregular glands, intraluminal papillary tufting, luminal necrosis) and cytological atypia (loss of polarity, high nuclear cytoplasmic ratio, nuclear rounding with prominent nucleoli, atypical mitosis) .

Another diagnostic challenge was a call for carcinoma Vs high grade dysplasia. 4 cases (4.9%) signed out as adenocarcinoma turned out be high grade dysplasia on review.

According to WHO (2019): "The defining feature of colorectal carcinoma is invasion through muscularis mucosae into sub-mucosa"[1].
 

Recommendation: Use the term high grade dysplasia instead of carcinoma when true invasion is not present or cannot be assessed.
One of the reporting errors encountered during review was missing comment on lymphovascular invasion (2 cases, 2.5%) and margin status (41 cases, 50.6%) in intact polyps. Lymphatic invasion as defined by WHO (2019) 5th Edition is "presence of single or groups of tumor cells in channels lined by endothelial cells and devoid of erythrocytes". 

Recommendation: It is important to comment on lymphatic invasion as it is an important risk factor for lymph node metastasis. Vascular invasion can be intramural (within the bowel wall) and extramural (outside the bowel wall) and is an indicator of worst outcome. Assessment of margin clearance is mandatory as positive margin is associated with local recurrence.
Another reporting discrepancy encountered was the use of non-standardized terminologies like "Adenomatous polyp" observed in 21 cases (25.9%) .

Recommendation: Conventional adenomas should ideally be categorized as tubular, villous or tubulovillous adenomas with a comment on presence or absence of high grade dysplasia. The correct subtyping is critical because higher proportion of villous architecture increases likelihood of developing carcinoma.

Overcalling hyperplastic polyps was one of the commonest reporting discrepancies observed in 10 cases (12.3%). Although goblet cell rich hyperplastic polyps mimic normal colonic mucosa with endoscopic impression of polyp. There are certain morphological features which need to be assessed with caution. The diagnostic criteria for hyperplastic polyp as described by WHO 2019 is “The presence of funnel shaped crypts with serrations limited to upper two-third. The proliferation zones are located in basal third of crypts with small basally located nuclei and no dysplasia” [9]. Basal dilatation and significant distortion should be absent in hyperplastic polyps. 

Recommendation: Use of terminologies like "Polypoidal mucosal fragments with hyperplastic change" should be avoided. Don't get swayed by colonoscopy impression of polyp as diminutive polyps are commonly encountered on colonoscopy with a minimal risk of serious pathology [10].

The histological assessment of colorectal polyps has become ever more complex by the recently described new entities by A C Bateman [3] i.e. Mucin-rich traditional serrated adenoma (MR-TSA) and serrated tubulovillous adenoma (S-TVA). The polyps with mixed morphology add further to diagnostic challenges.

Histomorphologically, MR-TSAs contain goblet cells in more than half of epithelium, little ectopic crypts and undulating serrations. MUC5AC is more commonly expressed in MR-TSAs than TSAs. In contrast to TSAs, MR-TSAs harbor BRAF mutations (75%) [3] more commonly than KRAS (26%) [3].

STVAs demonstrate characteristic features of conventional adenomas. The contrasting feature is prominence of ectopic crypts. A minimum of 50% of lesion should contain ectopic crypts. The features characteristic of traditional serrated adenoma like undulating serrations and abundant eosinophilic cytoplasm are not present. Nuclear positivity of B-Catenin is expressed in STVAs. STVAs harbor KRAS mutation and BRAF mutation is quite rare. The mixed polyps most commonly encountered include the hyperplastic polyps or sessile serrated lesions with conventional adenoma [3,7]. According to a study performed on BRAF V600E stain, the stain is negative in adenomatous component of polyp in 83% of mixed sessile serrated lesions with adenomatous dysplasia. This pattern of staining suggested that these are coalescent polyps likely occurring in close vicinity but independently arising as two separate lesions. But determination of exact spectrum of mixed polyps is still in evolution [11,12].

The 6 key parameters that contribute to accurate diagnosis and reduction of errors.
1.    The pathologist’s knowledge and experience about the subject.
2.    Correlation with clinical history.
3.    Strict adherence to standardized diagnostic and reporting criteria’s.
4.    Confirmation by immunohistochemical and molecular studies.
5.    Second opinion/ Intradepartmental consultation.
6.    Developing a culture of regular audits and feedback to signing out pathologist.

The quality assurance audit we performed highlighted the missing data elements in reported cases falling short of standardized CAP guidelines. Furthermore, diagnostic difficulties and discrepancies were also addressed to ensure safe reporting practices in terms of patient management. Still genetic testing and molecular analysis are highly desirable to hit the target of accurate diagnosis.

Conceptualization: Dr. Muddassar Hussain, Data Curation: Dr. Madiha Syed, Formal Analysis: Dr. Muddassar Hussain, Dr. Usman Hassan, Funding Acquisition: Not required, Investigation: Dr. Madiha Syed, Methodology: Dr. Madiha Syed, Dr. Usman Hassan, Dr. Muddassar Hussain, Project Administration: Dr.Muddassar Hussain, Dr. Usman Hassan, Resources: Shaukat Khanum Hospital, Software: Shaukat Khanum Hospital , Supervision: Dr. Muddassar Hussain, Dr. Usman Hassan, Validation: Dr. Usman Hassan, Dr. Muddassar Hussain, Visualization: Dr. Muddassar Hussain, Writing-Original Draft: Dr. Madiha Syed, Writing-Review & Editing: Dr. Madiha Syed.

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Corresponding Author: Dr. Madiha Syed, Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan.

Copyright: © 2021 All copyrights are reserved by Madiha Syed, published by Coalesce Research Group. This This work is licensed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.