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Understanding Barrett's Esophagus
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Definition
Diagnosis
Dysplasia
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Images for Pathologists

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Grading Dysplasia in Barrett's Esophagus
Images For Pathologists: Based on a Large National
Study Centered at Johns Hopkins

Introduction  |  Images  |  Follow-Up Information  |  Follow-up Images  | 



Images of Barrett's Esophagus

[Click on image for larger size.]

Figure 1.



With one exception, all reviewers interpreted this biopsy as Barrett's esophagus with no dysplasia. This single reviewer interpreted this as "indefinite for dysplasia on first review and as low-grade dysplasia on the second one. A suggestion of nuclear stratification on the right side of the illustration was interpreted by the other 11 reviewers as tangential sectioning. Note that the nuclei in deeper portions of the biopsy are more hyperchromatic than those at the surface and mitoses are also featured in deeper glands.
Consensus meeting diagnosis- no dysplasia.

Figure 2.


 

Agreement on the interpretation of "Indefinite for Dysplasia" was overall infrequent but good for this case. Noting that each case was reviewed twice by each of 12 observers, there were 24 interpretations per case. The interpretations for this case: No dysplasia - 2, Indefinite for dysplasia - 15, Low-grade dysplasia - 7. The interpretation at the consensus meeting: Indefinite. Despite prominent hyperchromasia, glandular crowding, increased mitotic activity, and cytologic atypia in the deeper aspect of the biopsy, there is maturation at the surface.
Figure 3.



Low- grade dysplasia. Interpretations: Indefinite - 2, Low-grade - 21, High-grade - 1. Consensus - Low-grade. The lack of surface maturation was the key factor in classifying this as dysplastic and the general lack of architectural complexity and maintenance of nuclear polarity would lead to an interpretation of low rather than high-grade dysplasia.
Figure 4.



Low-grade dysplasia. This lesion resembles a tubular adenoma of the lower gastrointestinal tract, a pattern occasionally seen in the setting of Barrett's esophagus. It was diagnosed as follows: Low-grade dysplasia - 20, High-grade dysplasia - 4. Consensus - Low-grade.
Figure 5.






This case was reviewed following the consensus conference and most interpretations were of low-grade dysplasia (14). However, there were 5 of indefinite and 5 of high-grade dysplasia.
Figure 6.



High-grade dysplasia. Diagnoses: Low-grade - 4, High-grade - 18, Intramucosal carcinoma - 2. Consensus - High-grade. This lesion features architectural complexity, prominent nuclear atypia, loss of nuclear polarity, and lack of appreciable surface maturation. The basement membranes of individual glands appear to remain intact, so most observers would not regard this as intramucosal carcinoma.
Figure 7.




As in the case of "Indefinite for dysplasia", there was little consensus surrounding the interpretation of Intramucosal carcinoma. The term "Intramucosal carcinoma" is applied to the earliest invasive carcinomas, i.e. lesions that invade through the basement membrane and infiltrate the lamina propria but not the muscularis mucosae. The superficial nature of mucosal biospies obviously limits the ability to distinguish such lesions from deeply invasive ones. Distinction from high-grade dysplasia is also subjective, although identification of syncytial arrangements of cells and complex glandular budding is believed to reflect early invasion (before desmoplasia becomes well-developed). The case depicted here may represent such a situation. Diagnoses: High-Grade - 5, Intramucosal carcinoma - 17, Frankly Invasive carcinoma - 2. Consensus - Intramucosal carcinoma.
Figure 8.




Invasive Carcinoma. Diagnoses: Intramucosal carcinoma - 1, Frankly invasive carcinoma - 23. Consensus - Invasive carcinoma. With well-developed desmoplasia, there was little disagreement in interpretation of this biopsy.
Figure 9.






A range of interpretations was offered for this lesion on the worksheets circulated prior to the consensus meeting: No dysplasia - 3, Indefinite - 3, Low-Grade - 8, High-Grade - 9, Invasive carcinoma - 1. Diagnosis derived at the consensus meeting: - Low-Grade. There is poor surface maturation, but architectural complexity is lacking and scattered neutrophils are embedded in the mucosa (arrowhead). This case illustrates some of the problems posed by inflamed specimens.
Figure 10.


Most of the reviewers were accustomed to formalin fixed material and found the Hollande's fixed specimens difficult to interpret. This lesion has somewhat complex architecture but is crushed. At first glance, the nuclei appear markedly enlarged, but in reality form a monolayer along the basement membrane in most sites and are simply more prominent than formalin-fixed nuclei. Diagnoses prior to the consensus meeting: Low-grade - 11, High-grade - 10, Intramucosal carcinoma - 3. Consensus meeting diagnosis - Dysplasia, Cannot Grade.
Figure 11.




This markedly ulcerated specimen resulted in a wide range of diagnoses prior to the consensus meeting. No dysplasia- 6, Indefinite - 4, Low-Grade - 2, High-Grade - 3, Intramucosal carcinoma - 4, Invasive carcinoma - 5. Consensus meeting diagnosis - Cannot Grade, difficult to evaluate. Rebiopsy indicated.
Figure 12.




Diagnoses: Indefinite - 3, Low-grade - 11, High-grade - 10. Consensus meeting diagnosis - Low-grade. This crowded focus appeared in a background of what all observers agreed was low-grade dysplasia. Despite its architectural complexity, the individual cells have abundant cytoplasm and maintain generally normal polarity.
Figure 13.




Diagnoses prior to meeting: Low-grade - 15, High-grade - 9. Consensus meeting (multi-headed microscopy session) diagnosis- High-grade. All observers agreed that dysplasia was present. The surface features were those of low-grade dysplasia and most observers interpreted this lesion as low-grade dysplasia on individual review. However, as a group, there was agreement that the prominent cytologic atypia and loss of nuclear polarity in the deep portions of the biopsy warranted an interpretation of high-grade dysplasia.
Figure 14.




Diagnoses: Indefinite - 3, Low-grade - 6, High-grade - 7, Intramucosal carcinoma - 8. Consensus meeting diagnosis- Dysplasia, Cannot grade. This biopsy shows surface hyperchromasia and crowded glands but the latter are composed of bland-appearing cells with relatively abundant cytoplasm.
 
  
  
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