Challenges for the crosstalk between endoscopists and pathologists

Diminutive colorectal polyps resected during endoscopy may sometimes by classified as normal tissue by pathologists, and this issue represents an important topic for the interdisciplinary crosstalk between endoscopists and pathologists. In this issue of Endoscopy, Ponugoti et al. [1] report on the disagreement between endoscopic and histological diagnoses of diminutive colon polyps. They compared 644 consecutive polyps ≤ 3 mm in size using endoscopic criteria and pathological assessment, and identified discrepancies in the classification and interpretation of such lesions. Clearly any discrepancy has quality assurance implications for both departments, but may also reflect the interaction and communication between the two specialities. The article ends with the clear statement that the findings provide evidence that pathology interpretation/assessment is not the gold standard for the management of lesions ≤ 3 mm in size.

This statement is quite provocative! But why not challenge interpretations if there is the possibility they could lead to improved quality assurance or introduction of a new quality marker? However, it is worth first having a closer look at the numbers provided and the numbers not provided in this article.

Approximately 15 % of adenomatous polyps verified independently by experienced gastroenterologists were diagnosed by pathology as normal mucosa. The possibility of mistaking lymphoid aggregates for polyps was rejected by the authors on the grounds that the difference is clear endoscopically, but it is not certain whether this distinction would be as obvious for less experienced endoscopists. The discrepancy in diagnoses is not new; several detailed publications have shown and analyzed this problem [2]. Previous studies have demonstrated that polyp tissue might only be apparent from the deeper cuts of tissue blocks during histopathological analysis [3], with one study calculating that further specimen cuts, costing an additional US$112, were necessary to change the diagnosis from “not representative” (normal) to “diagnostic” tissue [4].

“…the statement that histopathology is not the gold standard for management of lesions ≤ 3 mm …. is a product of local circumstances, the criteria used for diagnosis, and the specimen handling during both endoscopy and histopathological processing.”

Since 2002, it has been clear that most adenomas can be identified from tissue blocks cut to levels 7 or 8 [5]. This is the reason why guidelines nowadays recommend eight levels for bioptic specimens. For quality assurance, the size of a polyp has to be given in three dimensions including a description of the removal area, whether a stalk or a broad lesion is to be identified, and also whether coagulation marks can be seen histologically. In addition to these prerequisites, the pathologist always types and grades a polyp and answers the question of complete removal. For fragmented specimens, the total number of fragments and the total diameter have to be provided. It is recommended that piecemeal resection of colorectal polyps should be avoided. In the Ponugoti et al. study, polyps resected in a piecemeal fashion were correctly excluded from analysis, although the number of such resections was not reported.

The more surprising observation in the article is that more than 11 % (72/644) of pathology reports had no information on the number of the tissue pieces in the specimen container. Missing numbers and measurements may have serious implications in terms of auditing, especially if these are not single events but occur in substantial numbers. It would have been very constructive to question this issue with the pathology laboratory. Alternatively, this could be interpreted as the endoscopy unit being accustomed to these reporting shortcomings.

The recommendation that “when a high confidence adenoma is identified endoscopically and documented by photography, and the pathology report returns as normal, it is reasonable to manage the patient as if they had a conventional adenoma” is a pragmatic interpretation of the results [1]. However, more intense communication may resolve the situation. In addition, it is more usual nowadays for pathologists to use the terms “no pathology” or “no pathological diagnosis” or “no pathological changes” rather than “normal” as, in fact, it is still not clear what “normal is. The Helicobacter story is a good example of an entity that was eventually discovered to have pathogenic potential.

Publications from screening colonoscopies show that individuals with 1 – 2 adenomas measuring < 10 mm are at low risk of cancer and can return to the screening population rather than be referred for surveillance colonoscopies. In addition, European guidelines are more liberal than US guidelines, which recommend a follow-up colonoscopy after 5 – 10 years for polyps measuring < 10 mm [6]. The Ponugoti et al. study included only polyps 1 – 3 mm in size and there are no clear recommendations for such diminutive polyps. Thus, the study does not evaluate lesions that are inherently high risk, and as no numbers of lesions per patient were reported the relevance to individual patients cannot be assessed.

In the Ponugoti et al. study, 644 out of 900 lesions were selected, providing a large sample of adenomas measuring ≤ 3 mm in size. The remaining 256 lesions (28 %) were excluded because of suboptimal quality of the endoscopy photographs. This is quite a high proportion of images that did not meet the authors’ own quality criteria. Interestingly, the authors were able to show the histopathological results of these excluded lesions: 73.8 % were diagnosed as adenomas, 10.5 % as hyperplastic polyps, 0.8 % as inflammatory polyps, and 14.8 % were “normal” (no pathological changes). The authors state that there was no difference between the excluded and the included study lesions: 71.1 % adenomas, 13.2 % hyperplastic polyps, 0.3 % sessile serrated polyps, and 15.4 % “normal” (no pathological changes).

Of the 15.4 % samples showing normal mucosa (99 lesions), the pathologists asked for additional (deeper) sections to be cut in 24 cases, 4 (17 %) of which were adenomas; this changed the adenoma data but not by much. It would have been interesting to recut all of the tissue blocks, and maybe define the minimum number of deeper cut levels required to diagnose all possible pathological lesions.

The similarity of the histopathological diagnoses between the excluded and included lesions shows that, in fact, the pathologists were very consistent. If we now accept that there is no systematic error in the histopathological diagnosis itself, the observed results in the study can mean several things. Histopathology changes a three-dimensional structure (polyp) into a “shrunken” two dimensions specimen. Formalin shrinks small polyps by up to 50 %. This means that a 3-mm lesion becomes 1 – 2 mm and a 1-mm lesion, which is clearly visible endoscopically, may shrink down to half a millimetre during histopathological processing. This is an important point as it suggests that visibility may be an issue in pathology as well. In the case of small polyps, this can lead to the entire lesion being cut into sections or the entire lesion remaining within the block. Size does matter it seems, and this was nicely demonstrated by the authors, with adenoma being diagnosed in 60 % of 1-mm lesions rising to 79 % in 3-mm lesions.

It is also known that both the endoscopic and histological diagnoses of a lesion can vary substantially between observers [7] [8]. The fact that at least 28 % of all lesions were diagnosed as adenomas with high confidence in endoscopy but not by pathology may also lead us to question the criteria used in endoscopy. Both endoscopy and histopathology use morphology for making a (prediction of a) diagnosis. It is clear that there is always some space for subjective interpretation or human error in morphology. It is also known that if more than one morphologist agrees to a certain diagnosis then the more accurate the diagnosis is. This has been known for a long time in histopathology but is not always feasible. In the Ponugoti et al. paper, there is no doubt that the endoscopic criteria were very consistently checked by three experienced gastroenterologists. However, the article does not provide details about the procedures and criteria used by the participating pathologists.

In our opinion, several points could be learned from this paper.

1. Be pragmatic, and if there are discrepancies between endoscopy and pathology consider the lesion as an adenoma to ensure that the guidelines can be followed.

2. Ensure good communication between endoscopy and pathology departments. Both fields are working with different methods on the same lesion.

3. Discrepancies should be addressed as quality markers in audits.

4. Discrepancies should be worked up, first by phone, and then by recutting the tissue blocks.

5. Endoscopic criteria should be questioned when almost 30 % lead to a diagnosis other than adenoma in histopathology. An acceptable level should be defined.

The paper by Ponugoti et al. makes an important contribution to the field of diminutive colorectal polyps by challenging the quality of the crosstalk between endoscopists and pathologists. However, the authors’ statement that histopathology is not the gold standard for management of lesions ≤ 3 mm is more provocative than constructive. This editorial provides evidence that discrepancies in diagnoses may be a product of local circumstances, the criteria used for diagnosis, and the specimen handling during both endoscopy and histopathological processing. Good communication is a key first step, and we think it would be worthwhile, as a second step, to recut all remaining tissue blocks to assess whether these deeper levels harbor pathological changes that change the diagnosis. The number of recuts should be calculated to ensure that a safe diagnosis is possible. Further studies on the quality of the interaction between endoscopists and pathologists are highly warranted.

• References

• 1 Ponugoti P, Rastogi A, Kaltenbach T. et al. Disagreement between high confidence endoscopic adenoma prediction and histopathological diagnosis in colonic lesions ≤3 mm in size. Endoscopy 2019; 51: 221-226
• 2 Parameswaran L, Prihoda TJ, Sharkey FE. Diagnostic efficacy of additional step-sections in colorectal biopsies originally diagnosed as normal. Hum Pathol 2008; 39: 579-583
• 3 Wu ML, Dry SM, Lassman CR. Deeper examination of negative colorectal biopsies. Am J Clin Pathol 2002; 117: 424-428
• 4 Warnecke M, Engel UH, Bernstein I. et al. Biopsies of colorectal clinical polyps – emergence of diagnostic information on deeper levels. Pathol Res Pract 2009; 205: 231-240
• 5 Nash JW, Niemann T, Marsh WL. et al. To step or not to step: an approach to clinically diagnosed polyps with no initial pathologic finding. Am J Clin Pathol 2002; 117: 419-423
• 6 Martínez ME, Thompson P, Messer K. et al. One-year risk for advanced colorectal neoplasia: U.S. versus U.K. risk-stratification guidelines. Ann Intern Med 2012; 157: 856-864
• 7 Byrne MF, Chapados N, Soudan F. et al. Real-time differentiation of adenomatous and hyperplastic diminutive colorectal polyps during analysis of unaltered videos of standard colonoscopy using a deep learning model. Gut 2019; 68: 94-100
• 8 Lasisi F, Mouchli A, Riddell R. et al. Agreement in interpreting villous elements and dysplasia in adenomas less than one centimetre in size. Dig Liver Dis 2013; 45: 1049-1055