Pathology Associates Of Lexington, P.A.

Dysplasia in Barrett's Esophagus

2009 brought an outstanding article about biopsy features predictive of current, associated cancer in other areas of the endoscopic lesion⁴:

cribriform/solid growth in biopsy.
dilated dysplastic tubules containing necrotic debris in biopsy.
ulderated high grade dysplasia (HGD) in biopsy.
prominent polys infiltrating HGD in biopsy.
biopsy = dysplastic tubules which appear to be incorporated into squamous area.

As to BE, dysplasia is neoplastic transformation (as opposed to reactive atypia) of glandular epithelium that remains confined superficial to the epithelial basement membrane. Watch out!...a lot of gastroenterologists and referring clinicians confuse "atypia" with "dysplasia". If there are polys in exocytosis in the area of concern, the odds of overdiagnosis increase (and it may be best for the endoscopist to treat the condition with PPIs about 3 months or so & rebiopsy after inflammatory influences are reduced [S09-1759]). Sampling adequacy can always be a confounding variable (so, pay close attention to the reported size of the lesion relative to the number of biopsies). Low grade dysplasia is managed like an increased risk "marker" lesion by close endoscopic follow-up. Worse than low grade changes the category to "precursor" lesion & forces consideraftion of ablation.

dysplasia does not necessarily manifest hyperlayering.
dysplasia must affect the esophageal lumenal epithelium...there is a common non-dysplastic alteration of deeper gland epithelium that is simply part of the usual BE phenomenon.
dysplasia least commonly looks like epithelium of a colonic adenomatous polyp.
common dysplasia has enlarged cells with markedly hyperchromatic nuclei which commonly overlap and have irregular nuclear contours.
dysplasia should/must be discernible at low power (you don't have to "look hard" for it)...biopsy tinctorial variations or an abnormal gland architectural pattern may "catch the eye". Can't diagnose dysplasia when surface epithelium is "mature". [Is it low grade or high grade?...is it focal or diffuse?³]
be wary of making the diagnosis of dysplasia in presence of active inflammation, especially neutrophil exocytosis and/or adjacent ulcer.
even among experts involved in a consensus conference effort, the toughest diagnostic breakpoint is between "indefinite for dysplasia" and "low grade dysplasia"^{1,
2}.
> than 3cm lesion = "long segment BE; < than 3 cm = "short segment BE".
p53 IHC nuclear positivity favors high grade BE, but only 65% of high grade or even cancer is p53 positive; so, only use p53 to make you push up to high grade dysplasia from low grade³.

1988 Consensus Conference Criteria for Grading Dysplasia in BE²
Link to Johns Hopkins Histopathology Photos
Diagnosis	Criteria
"negative for dysplasia"	(1) Architecture normal. (2) Orderly cytology: orderly, basal nuclei /w normal N/C ratio, smooth nuclear envelope, any nucleoli are not markedly enlarged. Focal nuclear stratification is acceptable, as are small numbers of "dystrophic" goblet cells whose apical aspect does not communicate with the luminal surface (apical cytoplasmic mucous is usually present but may be reduced or absent in inflammation). Greater nuclear alterations are acceptable when associated with evidence of inflammation, erosion, or ulceration. Numbers of abnormal-appearing mitoses are variable. Normal nuclei appear more vesicular with more prominent nucleoli in Bouin and Hollande [& B5 or M2] fixatives than in formalin. Fixatives, therefore, must be considered in interpretation.
"indeterminate for dysplasia" (IND)	The architecture may be moderately distorted. Nuclear abnormalities are less marked than those seen in dysplasia. Other features that may lead to a diagnosis of IND include more numerous dystrophic goblet cells, more extensive nuclear stratification, diminished or absent mucus production, increased cytoplasmic basophilia, and increased mitoses. The diagnosis of IND should be limited to cases in which the changes are too marked for "negative" but not sufficient for the diagnosis of dysplasia.
"positive for dysplasia"	The diagnosis of LGD or HGD is based on the severity of both architectural and cytologic criteria that suggest neoplastlic transformation of the columnar epithelium. Although either architectural or cytologic abnormalities may predominate, HGD is diagnosed if either one is sufficiently prominent. Architectural abnormalities may include budded, branched, crowded, or irregularly shaped glands; papillary extensions into gland lumina; and villiform configuration of the mucosal surface. Nuclear features may include marked variation in size and shape, nuclear and/or nucleolar enlargement, increased nuclear-to-cytoplasmic ratio, hyperchromatism, and increased numbers of abnormal mitoses. Nuclear alterations are especially noteworthy if they involve the mucosal surface. Diagnostic features easily recognizable at lower power are cytoplasmic basophilia with loss of mucus and excessive nuclear stratification, often extending from the epithelial basement membrane to the luminal surface.
"carcinoma" (intramucosal or invasive)	Intramucosal carcinoma is defined as carcinoma that has penetrated through the basement membrane of the glands into the lamina propria but has not yet invaded through the muscularis mucosae into the submucosa. Most biopsy specimens will not be deep enough to rule out submucosal invasion.

[back to BE page]...[back to GI portal page]

References:

Goldblum, John R, chair of AP @ Cleveland Clinic, ASCP Teleconference 10/10/03, AV & handout (EBS).
Montgomery E, et. al., "Reproducibility of the Diagnosis of Dysplasia in Barrett's Esophagus: A Reaffirmation, Human Pathology 32(4):368-378, April 2001. [a study where 12 expert USA GI pathologists worked out criteria]
Lewin, David, "GI Tract Cases", 38th Pratt-Thomas Symposium in Surgical Pathology, 5 April 2005, Charleston, S. C.
McKenna BJ & Appleman HA, et. al., "A Histologically Defined Subset of High-Grade Dysplasia in Barrett Mucosa Is Predictive of Associated Carcinoma", AJCP 132(1):94-100, July 2009 (has excellent histopath. photos of features).

(posted 20 October 2004; latest addition 22 September 2009)