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Grading
Dysplasia in Barrett's Esophagus
Images For Pathologists: Based
on a Large National
Study
Centered at Johns Hopkins
Images of Barrett's Esophagus
[Click on image for larger size.]
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Figure
1.
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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. |
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Figure 2.
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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. |
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Figure
3.
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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. |
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Figure
4.
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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. |
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Figure
5.
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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. |
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Figure
6.
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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. |
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Figure
7.
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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. |
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Figure
8.
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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. |
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Figure
9.
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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. |
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Figure
10.
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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. |
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Figure
11.
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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. |
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Figure
12.
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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. |
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Figure
13.
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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. |
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Figure
14.
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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. |