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

does not distinguish it from gastric adenocarcinoma (812). PAS,
Alcian blue, and mucicarmine are histochemical stains that may
identify mucin in poorly differentiated adenocarcinoma.
Differential diagnosis
It can be difficult to distinguish a poorly differentiated adenocarcinoma
from a poorly differentiated squamous cell carcinoma
in a biopsy of a lower oesophageal tumour. Squamous cell
carcinomas are strongly positive for CK5/6, p63 (often > 75%
positive), and p40 (which is more specific than p63), whereas
adenocarcinomas are strongly positive for CK7 (often > 75%
positive) and negative for squamous markers. The diagnosis of
undifferentiated carcinoma should be considered for cases with
an equivocal immunohistochemical pattern and no morphologically
identifiable squamous or glandular features. Some poorly
differentiated adenocarcinomas may show neuroendocrine differentiation
(3515); such cases are more resistant to chemoradiation.
Preoperative chemoradiation can potentially complicate
diagnosis in two ways. Firstly, it can be difficult to distinguish the
mucinous component of oesophageal adenocarcinoma from
acellular mucin pools after neoadjuvant chemoradiotherapy
(613); cytokeratin staining to identify the carcinoma cells within
the mucin may be helpful in some instances. Secondly, treatment-associated
alterations of non-neoplastic epithelia may
include cytoplasmic and nuclear changes that mimic changes
in carcinoma cells. Atrophic and metaplastic glands may also
present diagnostic pitfalls (1786).
Cytology
The use of cytology for oesophageal tumour detection is
increasing (2415). Malignant glandular epithelial elements suggest
the presence of an adenocarcinoma, whereas malignant
squamous elements suggest squamous cell carcinoma. A mixture
of cytologically malignant squamous and glandular cells
should prompt suspicion for adenosquamous or mucoepidermoid
carcinoma.
Diagnostic molecular pathology
Not clinically relevant
Essential and desirable diagnostic criteria
Essential: evidence of glandular or mucinous differentiation
within an invasive tumour.
Desirable: immunohistochemistry (may be necessary to demonstrate
differentiation towards adenocarcinoma in poorly differentiated
lesions).
Fig. 2.14 Oesophageal adenocarcinoma. A Macroscopic appearance after neoadjuvant
chemotherapy. B An example previously treated with preoperative chemoradiation,
showing clear-cell change in the adenocarcinoma and calcification and foamy
macrophages in the stroma.
Staging (TNM)
There are two pathological staging systems in the eighth edition
of the AJCC cancer staging manual: one for adenocarcinoma
not previously treated with neoadjuvant therapy (pTNM) and
the other for adenocarcinoma after adjuvant therapy (ypTNM)
(1770,2707). In the ypTNM classification, stage grouping is not
affected by tumour grade or histological type. In early-stage
carcinomas, grade (either G1-2 or G3) is an important parameter
for determining stage. In patients who have received adjuvant
therapy, the survival differences among pathological stage
groups are less pronounced (1770,2707).
An adenocarcinoma in the upper Gl tract that infiltrates the
lamina propria or muscularis mucosae without invasion of the
submucosa is defined as intramucosal adenocarcinoma (pT1a).
Endoscopic resection with or without radiofrequency ablation is
the standard of treatment for early (pT1) oesophageal adenocarcinomas
that do not show adverse pathological features (251).
Adverse pathological features include submucosal invasion
(pT1b) to a depth > 500 pm, poor differentiation, lymphovascular
invasion, and margin involvement (2966). The presence of
duplicated and distorted muscularis mucosae, which is a consistent
finding in Barrett oesophagus, may lead to misinterpretation
of the depth of invasion of carcinoma (1720).
Regional lymph nodes are commonly the first sites of spread.
The current staging system for oesophageal adenocarcinoma
depends on the number of positive lymph nodes and therefore
relies on extensive lymph node sampling. Patients who have
received neoadjuvant therapy need more-extensive sampling,
42 Tumours of the oesophagus
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