OESOPHAGEAL TUMOURS

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Achille PICH
Principi della classificazione WHO
dei Tumori
PRIMITIVI
1) Tumori epiteliali benigni e lesioni
pseudotumorali
2) Tumori non-epiteliali benigni
3) Tumori epiteliali maligni
4) Tumori non-epiteliali maligni
SECONDARI
Epiteliali
Non-epiteliali
Histological classification WHO
Benign
Squamous cell papilloma
Viral wart
Adenoma
Epithelial tumours

Squamous cell carcinoma
Verrucous (squamous) carcinoma
Spindle cell (squamous) carcinoma
Histological classification WHO
Epithelial tumours
Malignant
Epithelial tumours

Adenocarcinoma
Adenosquamous carcinoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma


Small cell carcinoma
Undifferentiated carcinoma
Others
Malignant
Histological classification WHO
Histological classification WHO

Leiomyoma
Lipoma
Vascular tumours
Neurogenic tumours
Granular cell tumours
Others: GIST
Non-epithelial tumours
Benign
Histological classification WHO

Leiomyosarcoma
Kaposi sarcoma
Others
Non-epithelial tumours
Malignant
Histological classification WHO
Tumour-like lesions
Fibrovascular (fibrous) polyp
Cysts
Inflammatory polyp
Glycogenic acanthosis
Diffuse leiomyomatosis
Gastric heterotopia

Miscellaneous tumours
Malignant melanoma
Others
Carcinosarcoma
Secondary tumours
Histological classification WHO
Benign
Squamous cell papilloma
Viral wart
Adenoma
Epithelial tumours
Histological classification WHO

Leiomyoma
Lipoma
Vascular tumours
Neurogenic tumours
Granular cell tumours
Others: GIST
Non-epithelial tumours
Benign
Leiomyomas are the most common benign
tumors of the esophagus. In careful autopsy
cases, the frequency of this lesion has been
found to be almost 8%. Half of the surgically
excised cases are asymptomatic; dysphagia
and vague thoracic pain are the main
complaints in the others. The majority arise
from the inner circular muscle and are more
common in the distal third. Ulceration of the
overlying mucosa is a rare event, in contrast to
its common occurrence in gastric leiomyomas.
Local resection or enucleation is usually
successful.

EPITHELIAL
ABNORMALITIES
(Precancerous)
Dysplasia and carcinoma in situ
in squamous epithelium
Leukoplakia
Dysplasia
Grade 1
Grade 2
Grade 3
Carcinoma in situ

Squamous cell carcinoma
Verrucous (squamous) carcinoma
Spindle cell (squamous) carcinoma
Histological classification WHO
Epithelial tumours
Malignant
It is relatively common in China and other
Oriental countries (130/100.000) and is the
most common tumor of the alimentary tract
in the African Bantus (70/100.000). In the
United States it is less common (5.5% of
G.I. tumors).
Smoking (3-5x) and alcohol (50g/die: 4x;
100g/die: 20x) are two important and well-
known risk factors.
Squamous cell carcinoma of the esophagus
occurs more frequently in men (5:1) over 50
years of age.
Association may occur with squamous cell
carcinoma in other sites, particularly the
oropharynx and larynx

(12%); sometimes,
with gastric adenocarcinoma.
Association is described with lye strictures,
achalasia, Plummer Vinson syndrome, diverticula,
celiac sprue, tylosis (an auto-somal dominant
disorder characterized by hyperkeratosis of palms
and soles), and history of previous irradiation.
Increased incidence of esophagitis and a history of
previous gastrectomy is described in patients with
esophageal squamous cell carcinoma.
It has been suggested that HPV might play an
etiologic role in esophageal carcinogenesis
either by producing carcinogens or promotors
or by acting directly on the host cells. In
several studies, DNA sequences of HPV have
been found in a percentage (up to 60%) of
cases of esophageal squamous cell
carcinoma.
HISTOLOGICAL GRADING
G1
G2
G3
Well differentiated
Medium differentiated
Poorly differentiated
TNM Clinical Classification
Tis Carcinoma in situ/high grade dysplasia
T1 Lamina propria, muscolaris mucosae or
submucosa
T1a Lamina propria or muscolaris mucosae
T1b Submucosa
T2 Muscularis propria
T3 Adventitia
T4 Adjacent structures
T4a Pleura, pericardium or diaphragm
T4b Aorta, vertebral body, or trachea
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
N0 No metastasis in regional nodes
N1 Metastasis in 1-2 regional nodes
M0 No distant metastasis
M1 Distant metastasis
NX Regional nodes cannot be assessed
N2 Metastasis in 3-6 regional nodes
N3 Metastasis in 7 or more regional nodes
TNM Clinical Classification
STAGE GROUPING (1)
Stage 0
Stage IA
Stage IB
Stage IIB
Tis
T1
T2
T1, T2
N0
N0
N0
N1
M0
M0
M0
M0
T3 N0 M0
Stage IIA
STAGE GROUPING (2)
Stage IIIC
Stage IV Any T Any N M1
T4a M0 N1,N2
Stage IIIB
T3
T3
N1
N2
M0
M0
T4a N0 M0
T1,T2 M0
N2
Stage IIIA
T4b M0 Any N
Any T M0 N3
Prognostic Factors
Prognosis is very poor: the median survival after
diagnosis is less than 1 year.
1. Sex. Better survival in females.
2. Stage: is of paramount importance.
3. Microscopic grade: not substantial.
4. Other microscopic findings: vascular or
lymphatic invasion and marked tumor necrosis
worse prognosis; peritumoral fibrosis and
lymphocytic reaction better prognosis.
5. Surgical margins.
6. DNA ploidy and proliferation indices:
aneuploidy and high AgNOR counts
poor prognosis.
7. Epidermal growth factor receptor (EGFR).
Over-expression poor prognosis.
8. p53. Overexpression worse survival.

Squamous cell carcinoma
Verrucous (squamous) carcinoma
Spindle cell (squamous) carcinoma
Histological classification WHO
Epithelial tumours
Malignant
Verrucous carcinoma, morphologically
identical to its more common counterpart in
the oral cavity, has been described in the
esophagus.

It is grossly polypoid and well differentiated
throughout microscopically. Despite these
features and its inability to metastasize, the
mortality associated with this tumor is high.

Squamous cell carcinoma
Verrucous (squamous) carcinoma
Spindle cell (squamous) carcinoma
Histological classification WHO
Epithelial tumours
Malignant
Squamous cell carcinoma with spindle-cell
stroma (pseudosarcoma; carcinosarcoma;
spindle cell carcinoma; polypoid carcinoma)
usually presents as a large polypoid
neoplasm.
Metastases or recurrences supervene in
about 20% of the patients undergoing
surgery, and the overall survival rate is in
the neighborhood of 50%
The bulk of the tumor has a pleomorphic sarcoma-like
appearance. Most evidence suggests that this component
is also of epithelial derivation. Ultrastructurally, some of
these sarcoma-like cells in some of the tumors retain
epithelial markers, such as desmosomes and tonofibrils.
Immunohistochemically, keratin can be consistently
demonstrated in the epithelial-appearing component and,
in a high proportion of cases, also in some of the
sarcoma-like cells. The latter also exhibit strong reactivity
for vimentin and occasionally for actin and desmin.
Epithelial tumours

Adenocarcinoma
Adenosquamous carcinoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma


Small cell carcinoma
Undifferentiated carcinoma
Others
Malignant
Histological classification WHO
Esofagite da riflusso
The esophageal mucosa reacts to reflux by hyperplasia of the basal layer,
elongation of stromal vascular papillae, and infiltration with inflammatory
cells, often including eosinophils. Complications include ulceration,
stricture and replacement of the squamous epithelium by columnar
epithelium, a metaplastic process that results in:
Barrett's esophagus
This occurs in about 10% of patients with reflux esophagitis and is
significant because 5-10% of such patients develop adenocarcinoma.
Barrett's mucosa may be of cardiac, fundal, or intestinal type. Usually a
mixture of all three types is present. Adenocarcinoma appears to arise
predominantly in the intestinal type mucosa with dysplasia as a precursor
lesion. Complications other than carcinoma include ulcer and stricture.
Adenocarcinoma of the esophagus can arise
from Barrett's metaplastic mucosa,
from a focus of heterotopic gastric mucosa,
or, theoretically, from esophageal glands.

Adenocarcinomas make up about 10% of
esophageal cancers, but their relative
frequency seems to be on the rise (40%).


A very small proportion of primary
esophageal adenocarcinomas have signet
ring cell features.
Epithelial tumours

Adenocarcinoma
Adenosquamous carcinoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma


Small cell carcinoma
Undifferentiated carcinoma
Others
Malignant
Histological classification WHO
Small cell carcinoma (neuroendocrine
carcinoma; anaplastic small cell carcinoma)
is a highly malignant esophageal tumor
composed of anaplastic small cells.
Argyrophilic granules can be demonstrated.
Some cases have been associated with ACTH
and serotonin production.



The prognosis is very poor; most patients die
quickly with generalized metastases.
Histological classification WHO
Tumour-like lesions
Fibrovascular (fibrous) polyp
Cysts
Inflammatory polyp
Glycogenic acanthosis
Diffuse leiomyomatosis
Gastric heterotopia

Miscellaneous tumours
Malignant melanoma
Others
Carcinosarcoma
Secondary tumours
Malignant melanoma can be located at any level
in the esophagus, but it has a predilection for the
lower third.
Grossly, the tumor is usually large and has a
prominent polypoid appearance.
Microscopically, epithelioid, spindle-cell, and
pleomorphic areas may be seen singly or in
combination. The amount of melanin produced is
highly variable. Immunohistochemically, S-100
protein and HMB 45 positivity are the rule.
The prognosis is exceedingly poor.
Histological classification WHO
Tumour-like lesions
Fibrovascular (fibrous) polyp
Cysts
Inflammatory polyp
Glycogenic acanthosis
Diffuse leiomyomatosis
Gastric heterotopia

Miscellaneous tumours
Malignant melanoma
Others
Carcinosarcoma
Secondary tumours
Esophageal cysts are classified into:

- inclusion cysts (lined by squamous or
columnar epithelium, sometimes ciliated),
- retention cysts or mucoceles (arising from
cystic dilatation of submucosal glands), and
- developmental cysts (of esophageal,
bronchial, or gastric origin).


Cases of squamous cell carcinoma or
adenocarcinoma arising in such cysts have
been reported