An abnormal columnar-lined esophagus (CLE) is characterized by the presence
of cardiac mucosa (CM), oxynto-cardiac mucosa (OCM), and intestinal metapl
astic epithelium (IM) between gastric oxyntic mucosa and esophageal squamou
s epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37
biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies
. Detailed mapping of the distribution of epithelial types within the CLE s
howed a distinct zonation of epithelial types, CM was present throughout th
e CLE, whereas OCM and IM tended to occur in the distal and proximal part o
f the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at t
he most proximal level, compared with 22 of 32 patients (40 of 102 biopsies
) in the most distal level biopsies. The density of goblet cells was highes
t in the most proximal level. The differences in prevalence and density of
goblet cells between most proximal and most distal level biopsies were high
ly significant. These data suggest that for a given number of biopsies with
in the CLE, the likelihood of finding IM is greatest when the biopsies are
concentrated in the most proximal area of the CLE. We suggest that glandula
r transformation of squamous epithelium results in CM, which evolves into O
CM and IM by development of specialized parietal cells and goblet cells, re
spectively. The severity and nature of reflux cause these epithelial transf
ormations in a constant and predictable manner. Recognition of these change
s permits the development of morphologic definitions of reflux disease and
the characterization of the sequence of epithelial changes that represent t
he reflux-adenocarcinoma sequence.