What is the definition of dysplasia, as it applies to Barrett's mucosa?
R.H. Riddell (Hamilton)
The definition of dysplasia in Barrett's esophagus is that first developed for use in dysplasia in ulcerative colitis , Dysplasia is defined as an unequivocal neoplastic alteration of the epithelium. It should be stressed that such dysplastic epithelium not only may be a marker or precursor of carcinoma, but may itself be malignant and associated with direct invasion into the underlying tissue. Using this definition all
biopsies can be classified as negative, indefinite or positive for dysplasia by asking two questions:
1. Is the biopsy unequivocally negative for dysplasia?
2. Is the biopsy unequivocally dysplastic?
By definition, if the answer to both of these questions is "no" then one is dealing with mucosa that is indefinite for dysplasia.
Further, if required, dysplasia can itself be subdivided objectively into high grade and low grade depending on the position of the nuclei within the cell. In low grade dysplasia nuclei are largely confined to the basal halves of the cell, whereas in high grade dysplasia they regularly reach the upper part of the cell. While it is advised that the worst area of the biopsy be used for grading, the qualifying adjectives largely and regularly provide a subjective component and a potential area for inter-observer disagreement between pathologists. Nevertheless, interobserver agreement between pathologists has been tested and been shown to be quite good , with approximately 85% agreement in distinguishing high grade from other forms of dysplasia. If one bears in mind that a spectrum of changes is being observed, one expects a normal distribution curve for the results of many pathologists examining a single slide. In low grade dysplasia there is the potential for overlap between high grade dysplasia at one end and indefinite for dysplasia at the other, depending on the breadth of the distribution curve. The hope is that areas of overlap with adjacent grades in the spectrum do not occur; however, this is an unrealistic expectation. Some slides can be deliberately selected that straddle different parts of the grading spectrum; unselected biopsies can clearly do the same.
Perhaps the most important feature that disagreements have is their implication on patient management. The criterion for therapeutic intervention is usually intramucosal or invasive carcinoma. It might be expected that there would be no disagreement between pathologists regarding these diagnoses. Surprisingly, in one study agreement for intramucosal carcinoma was reached in only 87% of cases .
Clearly there are other problem areas. One is in recognizing features of active repair at the cytological level, which to the untrained eye can resemble dysplasia. A second is that repair can also lead to glandular proliferation producing a back-to-back or gland within gland appearance that can also be in carcinoma in situ (CIS), although without the typical cytological features accompanying carcinoma in situ. Nevertheless the potential for misreading CIS as reactive changes can be appreciated.
This definition of dysplasia has several direct implications that are imperative to understand. The most important of these is that dysplasia of any grade can give rise directly to an invasive carcinoma. Initially this flies in the face of traditional teaching that invasion occurs on a background of dysplasia that goes successively from low to high grade, which includes carcinoma in situ, from which invasion occurs. However, the fact that invasion can occur directly from low grade dysplasia is an intrinsic part of the definition and, although relatively uncommon, is known to occur in virtually all organs. In deliberately choosing to follow any grade of dysplasia, one must be aware firstly that a lesion is being followed that has the potential to give rise directly to an invasive carcinoma and secondly that carcinomas in Barrett's epithelium are frequently invisible endoscopically, being found either incidentally on
random biopsy or in erection carried out for dysplasia . Nevertheless, there has been an unconfirmed report that multiple large particle biopsies can take the guesswork out of this clinical situation. That is, if sufficient biopsies are taken then the presence of intramucosal or invasive carcinoma can be detected histologically, so that unexpected carcinoma is not found incidentally in resected specimens .
3. Reid BJ, Weinstein WM, Lewin KJ et al. Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions. Gastroenterology 1988:94:81-90.