Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Diagnosis

How effective is cytology alone in detecting goblet cells?

D.A. Antonioli (Boston)

In screening patients with esophageal pathology, examination of cytologic specimens (obtained by brush, balloon, or abrasion techniques) offers several potential advantages over mucosal biopsy specimens: the ability to sample a larger area, very low risk of complications (such as hemorrhage or perforation), and rapid turnaround time for the diagnosis [1]. Although the use of esophageal cytology in screening patients for squamous and glandular dysplasia and malignancy has been implemented, the value of such specimens to detect Barrett's esophagus itself has not been extensively investigated.

In cytologic preparations, Barrett's epithelium characteristically consists of sheets of glandular cells having sharply defined and smooth edges. When visualized en face, this epithelium forms a honeycomb pattern. The glandular cell nuclei are benign or show only reparative changes; they are uniformly distributed within the epithelial sheets. The background is either clean or inflammatory in nature [2-4].

The diagnostic finding for the cytologic diagnosis of Barrett's esophagus is the detection of goblet cells. Their features are the same as their counterpart in histologic sections: they have a single large apical cytoplasmic mucin vacuole that distends the lateral cell border and compresses the nucleus into a crescent shape that becomes positioned at the cell membrane. All these features should be present before diagnosing the presence of goblet cells [1-4]. Knowledge of the location from which the specimen was obtained is crucial because the cytology of intestinal metaplasia (IM) of the gastric cardia is indistinguishable from Barrett's epithelium [1].

However, in clinical practice, brush cytology has proven to be of limited value in diagnosing IM in the distal esophagus. In three recent series, a positive cytology for goblet cells was detected in only 82% to 86% of histologically proven cases of Barrett's esophagus [3-5]. Major reasons for false-negative cytologies include sampling error and the presence of very short segments of Barrett's esophagus in which goblet cells may be sparse. Conversely, false-positive readings for the cytologic presence of goblet cells may also occur. This problem is related to the fact that in histologic sections of Barrett's esophagus, foci of surface mucous cells may have a somewhat distended lateral border. However, these cells lack nuclear compression and, because they contain neutral gastric-type mucin rather than acidic intestinal-type mucins, their apical cytoplasm stains eosinophilic rather than basophilic as in the case of goblet cells [6]. Difficulty arises because in Papanicolaou stains of cytologic brushings, the basophilic staining of goblet cell cytoplasm is lost; therefore, it may be difficult to distinguish true goblet cells from non-goblet surface mucous cells with a distended lateral border. A markedly distended lateral cell membrane and nuclear compression are, thus, necessary for the diagnosis of goblet cells on cytosmears [5].

In summary, esophageal cytology is of limited usefulness in detecting goblet cells. Examination of mucosal biopsy specimens remains the gold standard for diagnosing Barrett's esophagus.


1. Wang HH. Gastrointestinal tract. In: Cibas E, Ducatman D, eds. Cytology: diagnostic principles and clinical correlates. Philadelphia: WB Saunders, 1996:171-188.

2. Geisinger KR, Teot LA, Richter JE. A comparative cytopathologic and histologic study of atypia, dysplasia, and adenocarcinoma in Barrett's esophagus. Cancer 1992;69:8-16.

3. Robey SS, Hamilton SR, Gupta PK, Erozian YS. Diagnostic value of cytopathology in Barrett's esophagus and associated carcinoma. Am J Clin Pathol 1988;89:493-498.

4. Wang HH, Doria MI Jr, Purohit-Buch S, et al. Barrett's esophagus: the cytology of dysplasia in comparison to benign and malignant lesions. Acta Cytol 1992;36:60-64.

5. Wang HH, Sovie S, Zeroogian JM, et al. Value of cytology in detecting intestinal metaplasia and associated dysplasia at the gastroesophageal junction. Hum Pathol 1997;28:465-471.

6. Genta RM, Huberman RM, Graham DY. The gastric cardia in Helicobacter pylori infection. Hum Pathol 1994;25:915919.

Publication date: August 2003 OESO©2015