Gi Pathology, Lecture 2: Pathology Of The Stomach

Front 1

CONGENITAL ANOMALIES

Name 4

Back 1

Congenital Pyloric Stenosis
Gastric duplications,
Cyst and diverticula,
Ectopic pancreas

Front 2

CONGENITAL ANOMALIES

Congenital Pyloric Stenosis

Back 2

a concentric hypertrophy of the pyloric muscle leading to gastric outlet obstruction. It is more common in white males (M to F ratio 4:1), first born children, and in those with a family history or Turner's syndrome. The disease manifests itself a few weeks after birth with projectile, non-bilious vomiting, usually immediately after feeding. The loss of large amounts of gastric acid leads to dehydration and hyperkalemic alkalosis.

Front 3

CONGENITAL ANOMALIES

Gastric duplications, cyst and diverticula

Back 3

These lesions are uncommon and usually asymptomatic. All layers of the stomach are present, except in diverticula which lack a muscular layer.

Front 4

CONGENITAL ANOMALIES


Ectopic pancreas

Back 4

Nodules of ____________ are embedded in the gastric wall. These are usually incidental discoveries during surgery; only in rare cases do they lead to pyloric obstruction or other symptoms. They are composed predominantly of acinar tissue, islets being uncommon.

Front 5

GASTRITIS

Back 5

Inflammation of the gastric mucosa, like inflammation in most organs can be classified into acute and chronic. Most chronic ______ will start with an acute phase, and exacerbations of chronic ______ will clinically appear as an acute episode.

Front 6

GASTRITIS

Acute

(Name 2 Examples)

Back 6

o Acute hemorrhagic (aka erosive) gastritis
o Acute infectious gastritis (bacterial, viral)

Front 7

GASTRITIS

Chronic

(Name 4 Examples)

Back 7

o Autoimmune atrophic gastritis

o H. pylori gastritis

o Reactive (chemical) gastritis

o Others: idiopathic granulomatous gastritis, eosinophilic gastritis

Front 8

Acute Gastritis

Acute hemorrhagic (erosive) gastritis

Etiology

Back 8

This designation is applied to an injury pattern of the gastric mucosa characterized by focal mucosal necrosis in an otherwise normal stomach, leading to multiple mucosal erosions (erosions are distinguished from ulceration in that erosions involve only a fraction of the mucosa).

Front 9

Acute Gastritis

Acute hemorrhagic (erosive) gastritis

Associated with:

Back 9

associated with:

NSAIDs,
excessive alcohol consumption,
ischemia and shock,
CNS trauma
Burns

Front 10

Cushing ulcer(s)

Back 10

CNS trauma not uncommonly (15% incidence) leads to erosions; erosions that are extensive and ulcerate in such patients are called _____________.

Front 11

Curling ulcer(s)

Back 11

CNS trauma not uncommonly (15% incidence) leads to erosions; erosions that are extensive and ulcerate in such patients are called Cushing ulcer(s).

In patients with severe cutaneous burns, such lesions are known as Curling ulcer(s)

Front 12

Acute Gastritis

Acute hemorrhagic (erosive) gastritis

Clinical Presentation:

Back 12

The clinical presentation includes hematemesis, melena and perforation appearing 3 to 6 days after the inciting event.

Most cases of erosive gastritis present as multiple small dark red mucosal erosions, more numerous in the fundus than in the antrum. The antrum is often more extensively involved in cases related to NSAIDs and alcohol consumption. Cushing ulcers are usually single, large, and can occur in the stomach or duodenum.

Front 13

Acute Gastritis

Acute hemorrhagic (erosive) gastritis

Erosions are caused by

Back 13

- loss of mucus protection
- inhibition of prostaglandin secretion
- increased local acid secretion
- damage to local microcirculation (e.g., secondary to shock)

Front 14

Chronic gastritis

Define it:


What is the most common form

Back 14

Chronic inflammation of the gastric mucosa, ranging from mild superficial involvement to severe atrophy

H. pylori induced gastritis

Front 15

H. pylori induced gastritis

Preferentially involves:

Back 15

-Most common form of chronic gastritis

- Preferentially involves gastric antrum, but also other areas of the stomach

- Prevalence of _________ parallels that of chronic gastritis, and antibodies to ________ often found in patients with chronic gastritis

Front 16

Chronic gastritis

H. Pylori Gastritis

Histological associations:

Back 16

- Associated with chronic active inflammation of glands and lymphoid hyperplasia of the lamina propria

- Can lead to atrophic gastritis or intestinal metaplasia

- Chronic infection associated with increased risk of peptic ulcer disease, gastric carcinoma, and low-grade lymphoma

Front 17

Chronic gastritis

In the antrum, __________ refers to loss of gland depth; in the corpus, _________ is loss of parietal and zymogenic cells; ___________ refers to a change in differentiation state of the remaining cells

Back 17

Atrophy,
Atrophy,
Metaplasia

Front 18

If the type of mucus made by the neck cells in atrophic corpus glands changes to resemble that made in the antrum/pylorus, then this is called _____________

Back 18

mucous or pseudopyloric metaplasia

Front 19

If the gastric unit begins to undergo a completely different pattern of development, where the unit is populated by intestinal epithelial cells such as mucous goblet cells and Paneth cells, it is called ______________

Back 19

intestinal metaplasia

Front 20

Autoimmune Atrophic Gastritis

Back 20

- Diffuse atrophic gastritis of the fundus and body

- Antibodies to parietal cells and intrinsic factor with reduction or absence of gastric acid & protease secretions

- Increased serum gastrin – G cell hyperplasia

- ECL cell hyperplasia

Front 21

Chemical Gastropathy

Back 21

Chronic gastric injury from reflux of alkaline duodenal contents, bile reflux and pancreatic secretions
Common in patients with anastomoses between stomach and small bowel
Histologically characterized by foveolar hyperplasia, congestion and edema, and little inflammation

Front 22

Chronic gastritis

Chronic gastritis associated with Helicobacter pylori

Name a characteristic feature of H. pylori infection.

Back 22

lymphocytes organize in mucosal lymphoid follicles,

These lymphoid follicles are components of mucosa associated lymphoid tissue (MALT);

_________ (infection with this organism) increases risk for lymphomas arising in MALT (such lymphomas are called MALTomas).

Front 23

Chronic gastritis

Chronic gastritis associated with Helicobacter pylori

Potential complications of chronic infection:

Back 23

- peptic ulcer disease,
- carcinoma
- lymphoma

Front 24

Autoimmune gastritis

Back 24

associated with other autoimmune diseases such as Hashimoto thyroiditis and Addison disease

Front 25

Autoimmune gastritis

The antibodies to the parietal cells themselves target a subunit of the ___________ in the cell membrane, which is required for acidification.

Intrinsic factor is a glycoprotein synthesized and secreted by parietal cells. The antibodies against IF are of two kinds. One binds ________, preventing its coupling with _________.

Another type binds the ___________ complex, blocking uptake in the small intestine. The lack of B12 leads to pernicious (megaloblastic) anemia.

Back 25

H+-K+ proton pump

intrinsic factor, vitamin B12

intrinsic factor vitamin B12 complex

Front 26

The most striking pathological changes in autoimmune gastritis occur in the__________ of the stomach with relative sparing of the _________.

Back 26

body/fundus

antrum

Front 27

Autoimmune gastritis

In this setting, associated polypoid lesions often represent small neuroendocrine tumors. The diminished acid production leads to an increase in what?

Back 27

gastrin secretion and G-cell (gastrin producing cell) hyperplasia in the antrum

Gastrin in turn has a trophic effect on ECL cells (enterochromaffin-like neuroendocrine cells) in the body of the stomach leading to ECL hyperplasia, microcarcinoids, and rarely to clinically significant carcinoid tumors.

Front 28

Chemical Gastropathy

Back 28

- Chronic gastric injury from reflux of alkaline duodenal contents, bile reflux and pancreatic secretions

- Common in patients with anastomoses between stomach and small bowel

- Histologically characterized by foveolar hyperplasia, congestion and edema, and little inflammation

Front 29

Hyperplastic Gastropathy

Define

and name 2 subtypes

Back 29

- encompasses all gastric abnormalities in which there is marked thickening of the mucosa translating into prominent, cerebriform rugae as seen in endoscopic and/or radiologic examination of the stomach.

2 Subtypes
- Foveolar hyperplasia
- Parietal cell hyperplasia

Front 30

Hyperplastic Gastropathy
- Foveolar hyperplasia

Example:

Back 30

Ménétrier disease
- Lymphocytic Gastritis
- H. Pylori gastritis (rare)

Ménétrier disease most commonly affects middle-aged males and presents with food-related epigastric pain, weight loss and diarrhea. Most patients are hypo or achlorhydric and have non-selective loss of plasma proteins into the gastric lumen, which can lead to peripheral edema. In children, the disease is self limited and has been associated with CMV infection and allergic reactions. Those cases that show an intense lymphocytic infiltration are designated as hypertrophic lymphocytic gastritis. Rare cases of hyperplastic gastropathy have been associated with heavy colonization by H. pylori.

(proliferation of surface cells and mucus-secreting pit cells)

Front 31

Hyperplastic Gastropathy
- Parietal cell hyperplasia

Example:

Back 31

Zollinger Ellison syndrome secondary to gastrinoma

Z-E syndrome is a manifestation of elevated gastrin levels, usually secondary to a gastrinoma of the pancreas or duodenum. This leads to the proliferation of parietal cells. Hypergastrinemia also leads to ECL hyperplasia, microcarcinoids, or carcinoid tumors, much as described for autoimmune gastritis.
(pit/surface cells normal)

Front 32

PEPTIC ULCER

Define:

Where are they found:

Back 32

defined as lack of continuity of the mucosa of the stomach or small intestine, produced by damage due to acid secretion.

Loss of less than the entire thickness of the mucosa is considered erosion.

Rarely involves the gastric body; While most occur in areas lined by antral mucosa (e.g., lesser curvature) or in the proximal duodenum, they can also occur in the esophagus or jejunum or adjacent to areas of ectopic gastric mucosa.

Front 33

Peptic Ulcer 

Histology

Back 33

Fibrinopurulent exudate overlying necrotic tissue, inflammatory granulation tissue, and fibrous scar
Reactive, regenerative, or metaplastic changes in surrounding mucosa

Front 34

Peptic Ulcer Disease

Complications

Back 34

- Perforation (peritonitis, sepsis, pancreatitis etc.) - (duodenum > stomach) -->can lead to air in the abd. cavity (pneumoperitoneum)

- Hemorrhage (duodenal > gastric)
associated with recent NSAID intake

- Fibrosis and stenosis (e.g., pyloric obstruction --> hour glass stomach)

- No significant risk of malignant transformation

Complications of what?

Front 35

Carcinoma of the Stomach

3% of cancer deaths in the USA

Potential Roles of H. pylori and Antecedent Gastritis and Metaplasia

Back 35

H. pylori is often termed “necessary but not sufficient” for induction of most gastric CAs

H. pylori is the most common cause of chronic atrophy (other types of gastritis not as highly correlated)

Chronic atrophy (whether Hp remain or not) is a clear carcinoma precursor state

Front 36

Gastric Carcinoma

Gross Pathology

Three major growth patterns:

Back 36

- Polypoid or fungating
- Infiltrative
- Ulcerating

Front 37

Gastric Carcinoma

Gross Pathology

Polypoid or fungating

Back 37

Resemble right colon carcinomas
Most common in body and along greater curvature

They are usually large and can have an ulcerated bleeding surface.

Front 38

Gastric Carcinoma

Gross Pathology

- Infiltrative

Back 38

Diffuse (linitis plastica)

these lesions spread through the mucosa and submucosa creating plaque-like patches that flatten the rugae.

Involvement of the entire stomach produces the pattern of linitis plastica in which the stomach resembles a leather bottle.

Front 39

Gastric Carcinoma

Gross Pathology

Ulcerating

Back 39

Most common in antrum and cardia
Can be difficult to distinguish from peptic ulcers

Front 40

Benign vs Malignant Ulcers

Back 40

Carcinomas:
- are usually larger (most > 2cm at diagnosis)

- more often have irregular shapes (vs. round regular lesion in peptic ulcers)

- more often have thickened and asymmetric borders.(peptic ulcer borders are slightly or not raised and overhang the crater.)

- Tend to distort or displace the rugal folds, whereas the rugae usually radiate from benign ulcers

biopsy is always necessary to establish a firm diagnosis.

Front 41

Gastric Carcinoma

Histological Types and Patterns

- Two major architectural patterns:

Back 41

Intestinal: cells look like colorectal cancer cells, displaying glandular formation, large columnar cells, and pushing borders;
and often arises in association with intestinal metaplasia

Diffuse: signet ring cells
small cells so stuffed with cytoplasmic mucin vacuoles that the nucleus is squashed against one aspect of the cell membrane, giving the cells their characteristic “signet ring” appearance.

Diffuse: E-cadherin mutations predominate, some familial forms

The cells show little to no intercellular cohesion (possibly related to mutated E-cadherin), which undoubtedly contributes to their diffuse, infiltrative pattern of growth. Diffuse carcinomas are more commonly seen in young patients (and have familial association with mutant E-cadherin genes),

Whereas both types are seen in the elderly population.

- Vast majority are adenocarcinomas (>95%)

Front 42

Carcinoma of the Stomach

Patterns of Spread

Back 42

- Regional lymph nodes,
- Supraclavicular node (Virchow)
- Ovaries (Kruckenberg),
- Lung and liver

Front 43

(Normally) Nonneoplastic mucosal lesions:

e.g., Fundic Gland Polyps

Back 43

- Usually very small
- Dilated glands lined by parietal and chief cells
- Associated with proton pump inhibitors (sporadic)
- Or with APC gene mutations (true neoplasms?)

Front 44

Other Tumors

Gastrointestinal Stromal Tumor GIST

Back 44

- Histogenetic relationship to interstitial cell of Cajal (pacemaker)
- Arise from muscularis or submucosa
- Spindle or epithelioid cell
- Poor prognosis predicted by large size (> 6cm), cytologic atypia, and high mitotic activity
- Express c-kit (CD117)

Front 45

Gastric Lymphomas

Back 45

- Most common site of GI tract lymphoma

- Most are MALTomas

- Most develop in setting of H. pylori infection and chronic gastritis

The stomach, normally devoid of resident lymphoid tissue is paradoxically the segment most frequently involved, accounting for 60% of all primary gastrointestinal lymphomas.

lymphoid tissue in the stomach appears as a consequence of chronic gastritis due to H. pylori.

Front 46

Gastric carcinomas spread to regional lymph nodes in the greater and lesser curvature and the portal region and to the liver, commonly, and other organs, less frequently, through the hematogenous rout. Metastasis of gastric carcinoma to the ipsilateral supraclavicular node is known as

Back 46

Virchow's node

Front 47

Krukenberg tumor

Back 47

the eponym applied to a signet ring cell carcinoma (of gastric, appendiceal or breast origin) metastatic to the ovary

Front 48

Malignant lymphoma

Microscopic examination demonstrates diffuse involvement of the mucosa by small lymphoid cells at different stages of maturation, many of which infiltrate the glandular epithelium forming the distinctive ___________

Back 48

lymphoepithelial lesions.

Front 49

T/F

Carcinoma directly arising in a gastric peptic ulcer is uncommon

Back 49

True

Front 50

T/F

Patients with gastric ulcers have about a two-fold increased risk for eventual development of gastric carcinoma somewhere in the stomach.

Back 50

True

Front 51

T/F

Patients with duodenal ulcers have a greater risk for developing non-cardiac gastric carcinoma.

Back 51

False

T/F

Patients with duodenal ulcers have a lower risk for developing non-cardiac gastric carcinoma.