Pagetoid spread of primary esophageal melanomas and several cases of pagetoid 
esophageal squamous cell carcinoma are known. However, true esophageal Paget 
disease (intraepithelial growth of neoplastic cells with glandular 
differentiation) has only rarely been reported. We encountered 3 endoscopic 
biopsy specimens containing Paget cells in squamous epithelium associated with 
adenocarcinomas in Barrett esophagus (BE) and in the esophagogastric junction. 
To determine the prevalence of Paget cells in the esophagus, we studied 81 
endoscopic mucosal resections and 27 esophagectomies from patients with invasive 
or intramucosal adenocarcinoma, and compared the findings to a control group of 
47 endoscopic mucosal resections and 25 esophagectomies from patients with 
high-grade dysplasia in BE. Paget cells were present in squamous epithelium 
overlying 5 (4.9%) of 108 adenocarcinomas but in none (0%) of 72 BE with 
high-grade dysplasia (P=0.16). A computerized search for primary Paget disease 
using the terms "Paget's and esophagus" or "pagetoid and esophagus" from 1994 to 
2007 did not yield any additional cases. Among the 8 patients with Paget cells 
(including the 2 index biopsies) there were no differences in either sex 
distribution (7M:1F) or age (mean 62.4 y) as compared with 103 adenocarcinomas 
without Paget cells (93M:10F, P=0.58; mean age 69.2 y, P=0.78). Morphologically, 
all adenocarcinomas with Paget cells contained at least a component of diffuse, 
poorly differentiated adenocarcinoma, and 1 was a signet ring cell carcinoma. 
Paget cells involved only squamous epithelium directly above the poorly 
differentiated tumor foci. Histochemistry for periodic acid-Schiff with diastase 
(PAS-D) and mucicarmine, and immunohistochemistry for CK7, CK20, p53, and 
E-cadherin, were performed on 7 Paget cases with the following results: PAS-D+ 
(7 of 7, 100%), mucicarmine+ (6 of 7, 86%), CK7+ (7 of 7, 100%), CK20+ (5 of 7, 
71%), p53 overexpression (3 of 7, 43%), and E-cadherin loss (complete loss in 1 
and faint expression in 3, 57%). Overall, PAS-D was the most efficacious stain 
for highlighting Paget cells. A control group of 19 adenocarcinomas without 
Paget cells were also stained for E-cadherin; only 1 showed faint expression 
(5%) and none showed complete loss (P=0.01). These results demonstrate a low but 
significant prevalence (4.9%) of Paget cells in esophageal and esophagogastric 
junction adenocarcinomas. Unlike previously described cases of mammary, vulvar, 
and perianal Paget disease, esophageal Paget cells are almost universally 
associated with underlying adenocarcinoma and not with high grade dysplasia ("in 
situ" disease) or primary Paget disease. A commonality among cases with Paget 
cells is the presence of focal or diffuse, poorly differentiated adenocarcinoma 
with discohesive cells. E-cadherin alterations seem to play a less significant 
role.