Dysplasia in Inflammatory Bowel Disease

As we all know, chronic inflammatory bowel disease (IBD) presents a risk for dysplasia and subsequent malignancy in patients with long standing disease.

The risk for adenocarcinoma increases with a number of factors including

• 
  
  the linear extent of disease within the bowel,
• 
  
  early age at onset of disease,
• 
  
  severity of disease and duration of disease.

The pathologic reporting of endoscopic biopsy specimens with inflammatory bowel disease must convey the information the clinician needs in a clear and consistent manner in order to properly manage the patient's disease.

Every biopsy report should, of course, give an assessment of the disease activity and distribution. In addition, the pathologist must render an opinion on the presence or absence of dysplasia. The "second line" diagnosis must reflect one of three choices regarding dysplasia in the biopsy:

1. Negative for dysplasia

2. Indefinite for dysplasia

3. Positive for dysplasia

• Low grade
• High grade

Agreeing on the terminology is relatively easy. Agreeing on the morphologic presence or absence of dysplasia is another issue.

Studies have shown poor interobserver reproducibility with regard to recognizing and diagnosing dysplasia. Low grade dysplasia (LGD), as one might guess, suffers from the worst interobserver variability.

The more marked the cytologic changes (high grade dysplasia) the easier it is to recognize and agree upon amongst pathologists.

This variability is one reason that many suggest surveillance for LGD. The histologic parameters which define dysplasia in the colon are consistent regardless of the subtype of IBD - Crohn's colitis or ulcerative colitis.

Negative for dysplasia

The lack of dysplasia in a chronic IBD biopsy is stated as "negative for dysplasia". That phrase should be included in biopsies that are completely normal or indistinguishable from non-IBD biopsies. This could be found in biopsies obtained from an area of the colon that is not affected by the disease or in an area that is completely quiescent perhaps from treatment.

Reactive changes that can and areseen in colitis biopsies are also included in the "negative for dysplasia" category. Some refer to such changes as "baseline atypia"; regardless, that limited spectrum is devoid of dysplasia and falls under the heading of "negative".

Indefinite for dysplasia

This category sometimes suffers from a lack of respect or credibility; however, it is a defined, accepted and even required category in properlyinterpreting dysplasia in IBD.

It is not a crutch upon which uncertain and weak willed pathologists lean. The changes that are included in the indefinite category must be recognized as such lest one either overcalls or undercalls dysplasia when it cannot be unequivocally determined whether it is present or absent. One such example is when dysplasia shows partial surface maturation. That is, the involvement of the surface epithelium by dysplastic change and not just the basal, proliferating portions of crypts is required to make a diagnosis of dysplasia. If the surface is partially involved or shows incomplete maturation then indefinite is the proper designation.

A biopsy that shows marked acute inflammation, erosion or ulceration that has cytologic changes that absent the inflammation would be called dysplastic must be designated as indefinite. This use is intended to recognize that the presence of inflammation makes diagnosing dysplasia with certainty nearly impossible.

Positive for dysplasia- low and high grade .

If there is flat dysplasia present in a biopsy, then one of the above choices (low grade or high grade) ought to appear in the report.

Criterias:

Low grade dysplasia: basally oriented nuclei; mild nuclear enlargement, nuclear crowding and hyperchromasia; decreased intracellular mucin High grade dysplasia: prominent nuclear stratification (compared to low grade) with many nuclei in luminal half of cell; more significant hyperchromasia and pleomorphism; may have marked architectural distortion with a villous or nodular growth pattern resembling adenoma or with cribriforming
The best tool that a pathologist has in effectively interpreting IBD biopsies for dysplasia is the most basic one - the simple hematoxylin and eosin stained tissue section. Ancillary tests such as immunohistochemistry have not proven as effective as the simple histologic evaluation of the H&E stain.

Experience of the pathologist in seeing and appropriately interpreting dysplasia in IBD biopsies is of critical importance.

Proper written and verbal communication between the gastrointestinal pathologist and the endoscopist is essential in going from the correct interpretation to the proper clinical course.

This is of paramount importance in interpreting polypoid dysplasia and distinguishing between a sporadic adenoma and a dysplasia associated lesion or mass (DALM).

SELECTED REFERENCES

• Riddell RH, Goldman H, Ransohoff DF, et al: Dysplasia in inflammatory bowel disease: Standardized classification with provisional applications. Hum Pathol 14:931-968, 1983.
• Bernstein CN, Blanchard JF, Kliewer E, et al: Cancer risk in patients with inflammatory bowel disease: A population-based study. Cancer 91: 854-862, 2001.
• Odze RD, Goldblum JR, Noffsinger A: Interobserver variability in the diagnosis of ulcerative colitis-associated dysplasia by telepathology. ModPathol 15:379-386, 2000.