WHO Classification of Tumours 5th Edition Digestive System Tumours by WHO Classification of Tumours Editorial Board (z-lib.org).1

encode transcription factors {3305). Larger studies are needed
to validate the potential use of these loci in screening for family
members affected by Barrett oesophagus or oesophageal
adenocarcinoma.
Pathogenesis
In response to the effects of acid/biliary reflux of gastric and
intestinal contents and dysbiosis (microbial imbalance), stem
cell and/or progenitor cells in the basal portion of the gastrooesophageal
epithelium are reprogrammed to columnar cell lineage
(3758,2626). The reparative epithelium develops into nongoblet
columnar epithelium (proximal gastric type). Over time,
this epithelium follows one of two lines of differentiation: either a
gastric pathway (parietal and chief cells) or an intestinal pathway
(goblet and Paneth cells) {2626J. The intestinal pathway, with
goblet cells, characterizes Barrett oesophagus. Recent studies
have shown that early Barrett neoplasia is always associated
with intestinal metaplasia (108). Barrett oesophagus may progress
through dysplasia to adenocarcinoma. The genetic and
epigenetic changes of progression from Barrett oesophagus
have been studied for decades {1399,1832,1831). Mutations of
some genes (TP53and SMAD4) occur in a stage-specific manner
and are restricted to high-grade dysplasia and adenocarcinoma
(3539,2759).
In recent years, next-generation sequencing techniques have
given rise to global projects involving whole-genome sequencing
of oesophageal adenocarcinoma {2585). These projects
have revealed key gene pathways and mutations involved in
pathogenesis (2923,915), identified novel genes (822), and
shown that the genomic landscapes of prechemotherapy and
postchemotherapy samples of oesophageal adenocarcinoma
are similar (2385). There are currently no clinical applications
for these comprehensive but complex data, but clinically relevant
and diagnostically useful prognostic and predictive markers
may emerge in the future. Data from The Cancer Genome
Atlas (TCGA) also suggest that oesophageal adenocarcinoma
strongly resembles gastric carcinoma with chromosomal instability
(475).
Macroscopic appearance
Oesophageal adenocarcinomas often present in advanced
stages and appear as stricturing, polypoid, fungating, ulcerative,
or diffuse infiltrating lesions. In earlier stages, adenocarcinomas
may appear as irregular plaques. Early-stage carcinomas
may present as small nodules or may not be detected on
endoscopy. Adjacent to the carcinoma, there may be irregular
tongues of reddish mucosa (resembling a salmon patch) that
represent Barrett oesophagus and reflux changes and that
contrast with the greyish-white colour of the squamous-lined
oesophageal mucosa.
Histopathology
Oesophageal adenocarcinoma shows gastric, intestinal, and
mixed (hybrid) lineage, evidenced by a combination of morphological
and immunohistochemical features (1565,426).
The mucosa adjacent to the adenocarcinoma may show Barrett
dysplasia and intestinal metaplasia (Barrett oesophagus).
Oesophageal adenocarcinomas can be classified as having
tubular, papillary, mucinous, and signet-ring cell patterns. Only
limited evidence of the relevance of these patterns is available;
therefore, patterns are described rather than subtypes. A mixture
of these patterns is often seen. The tubular pattern is most
Fig. 2.11 Oesophageal adenocarcinoma. A Tubular pattern. B Papillary pattern. C Mucinous pattern. D Signet-ring cell pattern.
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