Study: Health & Life Sciences or Biomedical Sciences (VU Amsterdam)
Supporting book: Robbins “Basic Pathology” (10th edition)
Chapter 15: The gastrointestinal tract (pages 590-636)
Oesophagus
The oesophagus consists of different layers:
E: squamous epithelium
L: lamina propria
MM: muscularis mucosa
S: submucosa
CM: circular muscular layer
Squamous epithelial cells are
all stacked upon on each
other. They divide, and
migrate to the surface where
they fall of.
ADENOCARCINOMA:
carcinoma that develops
out of glandular tissue
Development of oesophageal carcinoma
Oesophagitis → intestinal metaplasia → Dysplasia → Adenocarcinoma (Barret carcinoma)
Squamous cell carcinoma
Adenocarcinoma is the most prevalent cancer of the oesophagus. This can for example
develop because of a gag reflex, when the acidic compounds of the stomach touch the lining
of the oesophagus and the cells will differentiate into a tumour.
Let’s take a look at the steps (in blue) in more detail:
Oesophagitis (reflux)
When someone throws up, or drinks corrosive acids/ alcohol/ extremely hot fluids, the
stratified squamous mucosa of the oesophagus may be damaged. The morphological
changes are nonspecific, consisting of ulceration and acute inflammation. Irradiation causes
blood vessel damage adding an element of ischemic injury. You can also get oesophagitis
because of an infection.
1
,GERD, Gastroesophageal reflux disease, is the most common type of oesophagitis. when you
have Barret Oesophagus, you have an increased risk of developing an adenocarcinoma. This
is because of metaplasia and chronic inflammation.
The metaplasia takes place with the replacement of
(most of the times) intestinal epithelium.
Intestinal metaplasia
Squamous epithelium is replaced by intestinal type epithelium.
When this replace takes place, The oesophagus looks different
macro- and microscopic. The replaced parts are reddish because the epithelium is
inflamed. Microscopic, the intestinal metaplasia contains white bubbles with mucus
in them. This is normally not the case in squamous epithelium.
Dysplasia
This phase is still not invasive, but the cells in this state already harbour molecular
changes. These molecular changes are; a large irregular nucleus and a coarse
chromatin pattern. Remember that they remain in the place where they are
supposed to be.
Adenocarcinoma
This is the invasive state. The carcinoma forms a kind of polyp. You can recognize
smooth muscle fibres that are infiltrating in the muscular layer.
Risk factors for oesophageal adenocarcinoma are:
- Barret Oesophagus
- Tobacco users
- Obesity
- Radiation
- Patients with documented dysplasia
In nondysplastic Barret metaplasia, (epi)genetic changes can take place and these mutation
can accumulate during progression to dysplasia and invasive carcinoma. Often, chromosomal
abnormalities and TP53 mutations are present in the early stages.
Squamous cell carcinoma
First let’s look at the dysplasia of this carcinoma (non-invasive state).
Left, we see a normal state and right the dysplasia state. The epithelial line is bowed in the
2
,dysplasia state compared to normal, But the cells have not
infiltrated yet! So this is not a carcinoma (yet!).
Risk factors are use of alcohol and tobacco. Also, nutritional
deficiencies and exposure to mutagenic compounds or HPV
infection. The pathogenesis remains incompletely defined.
When it develops in a carcinoma, the microscopic image looks
like:
Gastric/stomach
The gastric mucosa consists of three layers:
- Foveolar layer: these are the gastric bits
- Glandular layer: these harbour different cells
- Smooth muscle
Corpus part of the stomach consists of:
Mucous cells protect the stomach against the acidic
environment.
Parietal cells serve for a different inflammation. They
form acid and intrinsic factor.
Antrum part of the stomach:
Mucous cells produce neutral glycoproteins
Hormone-producing cells that produce the hormone gastrin.
Inflammation of the gastric mucosa
- Acute gastritis
o H. pylori
This bacterium has a high prevalence in people. Mostly it goes unnoticed, but in
the long term it can induce neoplasia. First, no one believed any bacteria could
survive the acidic environment of the stomach, but this one does. Features of
the bacterium that are linked to its virulence are; its flagella, that allow the
bacteria to be motile in viscous mucous; urease, which generates ammonia from
endogenous urea, thereby elevating local gastric pH and therefore protecting
the bacteria; Adhesins, which enhance bacterial adherence to surface foveolar
cells; toxins, that may be involved in ulcer or cancer development.
o Alcohol
o NSAID (nonsteroidal anti-inflammatory drugs)
These inhibit cyclooxygenase -dependent synthesis of prostaglandins E2 and I2, which
stimulate nearly all of the above defence mechanisms including mucus and bicarbonate
secretion, mucosal blood flow, and epithelial restitution.
Gastritis results from mucosal injury. When neutrophils are present, the lesion is referred
to as Acute gastritis. It can be asymptomatic or cause variable degrees of epigastric pain,
nausea and vomiting. In more severe cases, there may be mucosal erosion, ulceration,
haemorrhage, hematemesis, melena, or rarely, massive blood loss.
3
, - Auto-immune gastritis
This is when you have antibodies against parietal cells and intrinsic factor. After this, the
epithelium will undergo intestinal metaplasia. This results in anaemia and an increased risk
for adenocarcinoma. (also neuro-endocrine hyperplasia and resulting risk for neuro-
endocrine tumour). AI gastritis typically spares the antrum and induces marked
hypergastrinemia. It is characterized by: reduced serum pepsinogen I levels; Antral endocrine
cell hyperplasia; Vitamin B12 deficiency leading to pernicious anaemia and neurologic
changes; impaired gastric acid secretion.
- Others
o Granulomatous gastritis, Crohn’s disease
o Lymphocytic gastritis
o Others
Gastric adenocarcinoma
The development of this carcinoma is similar to that of the adenocarcinoma in the
oesophagus.
Normal mucosa → Chronic gastritis → intestinal metaplasia → dysplasia → Gastric
adenocarcinoma
Mutations
Germline mutations in CDH1 (which encodes E-cadherin), are associated with familial gastric
cancers (diffuse type).
H. pylori
This bacterium can play a role in development of cancer, after inducing chronic gastritis.
Gastritis promotes the development and progression of cancers due to genetic alterations.
Epstein-Barr Virus (EBV)
10% of the gastric adenocarcinomas are associated with EBV infection. It is suggested that
EBV precedes neoplastic transformation.
Microscopic picture of this adenocarcinoma:
- Intestinal type
- Diffuse type
Here you can see the tumour is diffused everywhere. All the
epithelial cells are stained brown. They don’t stick together,
they are individual tumour cells and invade individually. These
tumour types have a very different clinical impact and are
more resistant to chemotherapy.
4
, Colorectum
Vascular disorders of the Bowel
- Intestinal ischemia can occur as a result of either arterial or venous obstruction
- Ischemic bowel disease resulting from hypoperfusion is most common at the splenic
flexure, sigmoid colon, and rectum; these are watershed zones where two arterial
circulations terminate
- Systemic vasculitis and infectious diseases can cause vascular disease that is not
confined to the gastrointestinal tract
- Angiodysplasia is a common cause of lower gastrointestinal bleeding in older adults
- Haemorrhoids are collateral vessels that form in response to venous hypertension.
Inflammatory intestinal disease
Inflammatory Bowel Disease (IBD)
This is a chronic condition resulting from complex interactions between intestinal microbiota
and host immunity in genetically predisposed individuals resulting an
inappropriate mucosal immune activation. It encompasses two entities:
- Crohn disease
Abundant neutrophils infiltrate and damage crypt epithelium. Clusters
of neutrophils within a crypt are often associated with crypt destruction.
- Ulcerative colitis
Granulomas are not present. Skip lesions are absent, and inflammation
generally is limited to the mucosa and superficial submucosa.
Tumours
First, some facts about GI (gastro-intestinal) tumours:
- GI tumours comprise 27% of all cancer related mortality
- High incidence
- Present in late stage of disease → poor prognosis
- For colorectal cancers a national screening between 55-75 year olds is done.
- With this screening, first stage colorectal cancers are being detected much faster.
Now, let’s look at the type of colorectal polyps:
Hyperplastic polyp
5
Supporting book: Robbins “Basic Pathology” (10th edition)
Chapter 15: The gastrointestinal tract (pages 590-636)
Oesophagus
The oesophagus consists of different layers:
E: squamous epithelium
L: lamina propria
MM: muscularis mucosa
S: submucosa
CM: circular muscular layer
Squamous epithelial cells are
all stacked upon on each
other. They divide, and
migrate to the surface where
they fall of.
ADENOCARCINOMA:
carcinoma that develops
out of glandular tissue
Development of oesophageal carcinoma
Oesophagitis → intestinal metaplasia → Dysplasia → Adenocarcinoma (Barret carcinoma)
Squamous cell carcinoma
Adenocarcinoma is the most prevalent cancer of the oesophagus. This can for example
develop because of a gag reflex, when the acidic compounds of the stomach touch the lining
of the oesophagus and the cells will differentiate into a tumour.
Let’s take a look at the steps (in blue) in more detail:
Oesophagitis (reflux)
When someone throws up, or drinks corrosive acids/ alcohol/ extremely hot fluids, the
stratified squamous mucosa of the oesophagus may be damaged. The morphological
changes are nonspecific, consisting of ulceration and acute inflammation. Irradiation causes
blood vessel damage adding an element of ischemic injury. You can also get oesophagitis
because of an infection.
1
,GERD, Gastroesophageal reflux disease, is the most common type of oesophagitis. when you
have Barret Oesophagus, you have an increased risk of developing an adenocarcinoma. This
is because of metaplasia and chronic inflammation.
The metaplasia takes place with the replacement of
(most of the times) intestinal epithelium.
Intestinal metaplasia
Squamous epithelium is replaced by intestinal type epithelium.
When this replace takes place, The oesophagus looks different
macro- and microscopic. The replaced parts are reddish because the epithelium is
inflamed. Microscopic, the intestinal metaplasia contains white bubbles with mucus
in them. This is normally not the case in squamous epithelium.
Dysplasia
This phase is still not invasive, but the cells in this state already harbour molecular
changes. These molecular changes are; a large irregular nucleus and a coarse
chromatin pattern. Remember that they remain in the place where they are
supposed to be.
Adenocarcinoma
This is the invasive state. The carcinoma forms a kind of polyp. You can recognize
smooth muscle fibres that are infiltrating in the muscular layer.
Risk factors for oesophageal adenocarcinoma are:
- Barret Oesophagus
- Tobacco users
- Obesity
- Radiation
- Patients with documented dysplasia
In nondysplastic Barret metaplasia, (epi)genetic changes can take place and these mutation
can accumulate during progression to dysplasia and invasive carcinoma. Often, chromosomal
abnormalities and TP53 mutations are present in the early stages.
Squamous cell carcinoma
First let’s look at the dysplasia of this carcinoma (non-invasive state).
Left, we see a normal state and right the dysplasia state. The epithelial line is bowed in the
2
,dysplasia state compared to normal, But the cells have not
infiltrated yet! So this is not a carcinoma (yet!).
Risk factors are use of alcohol and tobacco. Also, nutritional
deficiencies and exposure to mutagenic compounds or HPV
infection. The pathogenesis remains incompletely defined.
When it develops in a carcinoma, the microscopic image looks
like:
Gastric/stomach
The gastric mucosa consists of three layers:
- Foveolar layer: these are the gastric bits
- Glandular layer: these harbour different cells
- Smooth muscle
Corpus part of the stomach consists of:
Mucous cells protect the stomach against the acidic
environment.
Parietal cells serve for a different inflammation. They
form acid and intrinsic factor.
Antrum part of the stomach:
Mucous cells produce neutral glycoproteins
Hormone-producing cells that produce the hormone gastrin.
Inflammation of the gastric mucosa
- Acute gastritis
o H. pylori
This bacterium has a high prevalence in people. Mostly it goes unnoticed, but in
the long term it can induce neoplasia. First, no one believed any bacteria could
survive the acidic environment of the stomach, but this one does. Features of
the bacterium that are linked to its virulence are; its flagella, that allow the
bacteria to be motile in viscous mucous; urease, which generates ammonia from
endogenous urea, thereby elevating local gastric pH and therefore protecting
the bacteria; Adhesins, which enhance bacterial adherence to surface foveolar
cells; toxins, that may be involved in ulcer or cancer development.
o Alcohol
o NSAID (nonsteroidal anti-inflammatory drugs)
These inhibit cyclooxygenase -dependent synthesis of prostaglandins E2 and I2, which
stimulate nearly all of the above defence mechanisms including mucus and bicarbonate
secretion, mucosal blood flow, and epithelial restitution.
Gastritis results from mucosal injury. When neutrophils are present, the lesion is referred
to as Acute gastritis. It can be asymptomatic or cause variable degrees of epigastric pain,
nausea and vomiting. In more severe cases, there may be mucosal erosion, ulceration,
haemorrhage, hematemesis, melena, or rarely, massive blood loss.
3
, - Auto-immune gastritis
This is when you have antibodies against parietal cells and intrinsic factor. After this, the
epithelium will undergo intestinal metaplasia. This results in anaemia and an increased risk
for adenocarcinoma. (also neuro-endocrine hyperplasia and resulting risk for neuro-
endocrine tumour). AI gastritis typically spares the antrum and induces marked
hypergastrinemia. It is characterized by: reduced serum pepsinogen I levels; Antral endocrine
cell hyperplasia; Vitamin B12 deficiency leading to pernicious anaemia and neurologic
changes; impaired gastric acid secretion.
- Others
o Granulomatous gastritis, Crohn’s disease
o Lymphocytic gastritis
o Others
Gastric adenocarcinoma
The development of this carcinoma is similar to that of the adenocarcinoma in the
oesophagus.
Normal mucosa → Chronic gastritis → intestinal metaplasia → dysplasia → Gastric
adenocarcinoma
Mutations
Germline mutations in CDH1 (which encodes E-cadherin), are associated with familial gastric
cancers (diffuse type).
H. pylori
This bacterium can play a role in development of cancer, after inducing chronic gastritis.
Gastritis promotes the development and progression of cancers due to genetic alterations.
Epstein-Barr Virus (EBV)
10% of the gastric adenocarcinomas are associated with EBV infection. It is suggested that
EBV precedes neoplastic transformation.
Microscopic picture of this adenocarcinoma:
- Intestinal type
- Diffuse type
Here you can see the tumour is diffused everywhere. All the
epithelial cells are stained brown. They don’t stick together,
they are individual tumour cells and invade individually. These
tumour types have a very different clinical impact and are
more resistant to chemotherapy.
4
, Colorectum
Vascular disorders of the Bowel
- Intestinal ischemia can occur as a result of either arterial or venous obstruction
- Ischemic bowel disease resulting from hypoperfusion is most common at the splenic
flexure, sigmoid colon, and rectum; these are watershed zones where two arterial
circulations terminate
- Systemic vasculitis and infectious diseases can cause vascular disease that is not
confined to the gastrointestinal tract
- Angiodysplasia is a common cause of lower gastrointestinal bleeding in older adults
- Haemorrhoids are collateral vessels that form in response to venous hypertension.
Inflammatory intestinal disease
Inflammatory Bowel Disease (IBD)
This is a chronic condition resulting from complex interactions between intestinal microbiota
and host immunity in genetically predisposed individuals resulting an
inappropriate mucosal immune activation. It encompasses two entities:
- Crohn disease
Abundant neutrophils infiltrate and damage crypt epithelium. Clusters
of neutrophils within a crypt are often associated with crypt destruction.
- Ulcerative colitis
Granulomas are not present. Skip lesions are absent, and inflammation
generally is limited to the mucosa and superficial submucosa.
Tumours
First, some facts about GI (gastro-intestinal) tumours:
- GI tumours comprise 27% of all cancer related mortality
- High incidence
- Present in late stage of disease → poor prognosis
- For colorectal cancers a national screening between 55-75 year olds is done.
- With this screening, first stage colorectal cancers are being detected much faster.
Now, let’s look at the type of colorectal polyps:
Hyperplastic polyp
5
