What are nodules or masses that project above the level of the surrounding mucosa?
• They are identified in up to 5% of upper GI endoscopies.
gastric polyps
Polyps may develop as a result of or cell hyperplasia, inflammation, ectopia (congentital abnormal position), or neoplasia
epithelial
stromal
Up to 75% of all gastric polyps are what 2 kinds of gastric polyps?
inflammatory or hyperplastic polyps.
The distinction between inflammatory and hyperplastic polyps is based on the degree of
- They most commonly affect individuals between 50 and 60 yrs of age, usually arising in a background of gastritis that initiates the injury and reactive hyperplasia that cause polyp growth.
- If associated with H. pylori gastritis, polyps may egress/regress after bacterial eradication.
inflammation.
chronic
regress
What is happening in this slide?
hyperplasia
increased glands and stroma
The frequency with which dysplasia, a precancerous in situ lesion, develops in these polyps correlates with
• There is a significant increase in risk with polyps >
size.
1.5 cm.
Describe the photo:
top: intestinal metaplasia with goblet cells in polyp
bottom: High-grade dysplasia in a gastric hyperplastic polyp.
What type of polyp occur sporadically and in individuals with familial adenomatous polyposis (FAP).?
fundic gland polyps
Why has the incidence of sporadic fundic gland polyps lesions increased?
result of the widespread use of proton pump inhibitors.
• This likely results from increased gastrin secretion, in response to reduced acidity, and glandular hyperplasia driven by gastrin
Desribe the slide:
A: fundic gland polyps in stomach
B. fundic gland polyp
C: fundic gland polyp with parietal (a, pink) and chief cells (purple)
Fundic gland polyps are nearly always asymptomatic, and are usually an incidental finding.
• These well-circumscribed polyps occur in the gastric and , often are multiple, and are composed of cystically dilated, irregular glands lined by flattened and chief cells
body
fundus
parietal
What type of polyp represent up to 10% of all gastric polyps?
Gastric adenomas
Gastric adenoma incidence increases with and varies among different populations in parallel with that of gastric adenocarinoma.
- Patients usually are between 50 and 60 years of age, and males are affected 3 times more often than females.
- Adenomas almost always occur on a background of chronic gastritis with
and intestinal
age
atrophy
metaplasia.
All gastrointestinal adenomas exhibit epithelial , which can be classified as low- or high- grade.
• The risk for development of adenocarcinoma in gastric adenomas is related to the of the lesion and is particularly increased with lesions over
in diameter.
• The malignant potential of gastric adenomas is far lesser/greater than that of their colonic adenomas.*
dysplasia
size
2 cm
greater
What is noticed on this slide:
nuclear changes - larger nuclei, various shapes
What is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers?
Adenocarcinoma
As concerning adenocarcinoma:
Early symptoms resemble those of gastritis, including dyspepsia indigestion), dysphagia, and nausea.
• As a result, the cancer is seldom/often diagnosed at advanced stages when clinical manifestations such as weight loss, anorexia, altered bowel habits, anemia, and hemorrhage trigger diagnostic evaluation.
chronic
often
The incidence is up to times higher in Japan, Chile, Costa Rica, and Eastern Europe than in North America, northern Europe, Africa, and Southeast Asia.*
20
Gastric cancers are genetically heterogeneous/homogenous, but certain molecular alterations are common.
heterogeneous
As concerning gastric adenocarcinoma pathogenesis:
Germ line mutations in CDH1, which encodes , a protein that contributes to epithelial intercellular adhesion, are associated with familial gastric cancers, usually of the diffuse type
E-cadherin
CDH1 mutations that result in loss of E-cadherin can develop in which 2 ways?
germ line mutations of CDH1
sporadic diffuse gastric tumors (methylation of CDH1 promotor)
Thus, the loss of E-cadherin function seems to be a key step in the development of gastric cancer, whether germ line or sporadic.
diffuse
What is E-cadherin?
a protein that contributes to epithelial intercellular adhesion (zonula adherens)
(associated with familial gastric cancers, usually of the diffuse type).
Loss of E-cadherin promotes tumor .
invasion
Patients with familial adenomatous polyposis who have germ line mutations in genes have an increased risk for development of gastric cancer.
APC
intestinal-type
What sporadic type cancer is associated with several genetic abnormalities including acquired mutations of β-catenin, a protein that binds to both E-cadherin and APC protein; microsatellite instability; and hypermethylation of genes including TGFβRII, BAX, IGFRII, and p16/INK4a?
sporadic intestinal-type gastric cancer (adenocarcinoma)
mutations are present in a majority of sporadic gastric cancers of both histologic types (intestinal-type and diffuse)
TP53
Chronic gastritis, most commonly due to ,* promotes the development and progression of cancers that may be induced by diverse genetic alterations.
H. pylori infection
As is the case with many forms of chronic inflammation, H. pylori - induced chronic gastritis is associated with increased production of proinflammatory proteins, such as which two proteins?
interleukin-1β (IL-1β)
tumor necrosis factor (TNF).
Gastric adenocarcinomas are classified according to their in the stomach as well as gross and histologic morphology
location
The classification that separates gastric cancers into intestinal and diffuse types correlates with the distinct patterns of molecular alterations .
Lauren
Describe the drawing? What do each of the stomachs represent?
Top: intestinal type
Middle and Bottom: diffuse type
Which gastric adenocarcinoma type is being described:
tend to be bulky and are composed of glandular structures similar to esophageal and colonic adenocarcinoma.
- They typically grow along broad cohesive fronts to form either an exophytic mass or an ulcerated tumor.
- The neoplastic cells often contain apical mucin vacuoles, and abundant mucin may be present in gland lumina.
intestinal-type gastric adenocarcinoma
Which gastric adenocarcinoma type is being described:
-display an infiltrative growth pattern and are composed of discohesive cells with large mucin vacuoles that expand the cytoplasm and push the nucleus to the periphery, creating a signet ring cell morphology.
• These cells involve the mucosa and stomach wall individually or in small clusters.
diffuse gastric gastric adenocarcinoma
Which type of gastric cancer displays a signet ring morphology?
diffuse gastric cancers (adenocarcinoma)
A mass may be difficult to appreciate in diffuse gastric cancer, but these infiltrative tumors often cause a desmoplastic reaction that stiffens the gastric wall and may cause diffuse rugal flattening and a rigid, thickened wall that imparts a “leather bottle” appearance termed .
linitis plastica
Which gastric cancer is being described?
predominates in high-risk areas and develops from precursor lesions such as dysplasia and adenomas.
• The mean age at presentation is 55 years, and the male-to-female ratio is 2:1
Intestinal-type gastric cancer
Which gastric adenocarcinoma is relatively uniform across countries, there are no identified precursor lesions, and the disease occurs at similar frequencies in males and females?
diffuse gastric cancer
What are the most powerful prognostic indicators for gastric cancer?
depth of invasion
extent of nodal metastasis
Concerning gastric adenocarcinoma:
local invasion can occur in which 3 nearby structures?
duodenum
pancreas
retroperitoneum
What is the preferred method of treatment of gastric adenocarcinoma?
surgical resection
While extranodal lymphomas can arise in virtually any tissue, they do so most commonly in the gastrointestinal tract, especially the
Nearly 5% of all gastric malignancies are primary lymphomas, the most common of which are indolent extranodal marginal zone lymphomas.
• In the gut, these tumors often are referred to as lymphomas of MALT, or
stomach.
B-cell
MALTomas.
note: diffuse infiltrates of lymphoma cells
Describe the pathogenesis of Marginal Zone Lymphoma?
Chronic gastritis —> proliferation of polyclonal B cells
——-> Ag dependent polyclonal proliferation MALT lymphoma
————> Ag independent monoclonal MALT lymphoma
At which stage of MALT lymphoma pathogenesis are antibiotics an appropriate treatement and chemotherapy an appropriate treatment?
antibiotics = polyclonal proliferation of B cells (B slide)
Chemo = Monoconal proliferation of B cells (C slide)
Neuroendocrine tumors, also referred to as tumors, arise from neuroendocrine organs (eg, the ) and neuroendocrine-differentiated GI epithelia (eg, ).
carcinoid
endocrine pancreas
G cells
Why are neuroendocrine tumors called “carcinoid”?
more slower growing
Where are the most common places to find neuroendocrine tumors?
GI tract (40% in small intestine)
tracheobronchial tree
lungs
Neuroendocrine tumors are or submucosal masses that create small polypoid lesions.
• The tumors are yellow or tan in appearance and elicit an intense desmoplastic reaction that may cause of the bowel and obstruction.
intramural (within the wall)
kinking
On histologic examination, neuroendocrine tumors are composed of islands, trabeculae, strands, glands, or sheets of cells with scant, pink granular cytoplasm and a round-to-oval nucleus.
uniform
stippled
note: on the left is pink fibrosis, right are stippled uniform nuclei
The peak incidence of neuroendocrine tumors is in the decade, but they may appear at any age.
sixth
What produces the symptoms of carcinoid neuroendocrine tumors?
hormones
As related to neuroendocrine carcinoid tumors, what is being described?
vasoactive substances secreted by the tumor that cause cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis.
carcinoid syndrome
When tumors are confined to the intestine, the vasoactive substances released are to inactive forms by the liver - a “first-pass” effect.
• Thus, carcinoid syndrome occurs in <10%, of patients, and is weakly/strongly associated with metastatic disease.
metabolized
strongly
What are the 3 different subtypes of neurodendocrine (carcinoid) tumors?
Foregut neuroendocrine (carcinoid) tumor
Midgut neuroendocrine (carcinoid) tumor
Hindgut neuroendocrine (carcinoid) tumor
Which type of neuroendocrine (carcinoid) tumor is being described:
within the stomach, duodenum proximal to the ligament of Treitz, and esophagus, rarely metastasize and are generally cured by resection.
Foregut neuroendocrine (carcinoid) tumor
What are rare duodenal gastrin-producing foregut neuroendocrine tumors that may present with symptoms related to increased acid production, including pain and/ or bleeding from gastroduodenal ulcers (Zollinger-Ellison syndrome) refractory gastroesophageal reflux, and diarrhea due to inactivation of pancreatic enzymes by excessive gastric acid?
gastrinomas
Which type of neuroendocrine (carcinoid) tumor is being described:
neuroendocrine (carcinoid) tumors arise in the jejunum and ileum, are often multiple and tend to be aggressive.
• In these tumors, depth of local invasion, size, and the presence of necrosis and mitoses are associated with poor outcome.
Midgut neuroendocrine (carcinoid) tumors
Which type of neuroendocrine (carcinoid) tumor is being described:
- neuroendocrine (carcinoid) tumors arising in the appendix and colorectum are typically discovered incidentally.
- Those in the appendix occur at any age and almost uniformly pursue a benign course.
- Rectal tumors tend to produce polypeptide hormones and may manifest with abdominal pain and weight loss.*
Hindgut neuroendocrine (carcinoid) tumors
What is the most common mesenchymal tumor of the abdomen, and more than half of these tumors occur in the stomach?
Gastrointestinal stromal tumor (GIST)
note: the spindle shaped cells (mesenchymal in nature)
The most common genetic change underlying the pathogenesis of GISTs is -of-function mutations of the gene encoding the tyrosine kinase (CD-117), the receptor for stem cell factor (75%-85% of all GISTs)
An additional 8% of GISTs have mutations that activate a related tyrosine kinase, platelet-derived growth factor receptor A ().
gain
KIT
PDGFRA
Which gastrointestinal tumor is associated with mutations of KIT (receptor of stem cell factor) and PDGFRA (platelet derived growth factor receptor)?
gastrointestinal stromal tumor
Both sporadic and germ line mutations result in constitutively active KIT or PDGFRA receptor and produce intracellular signals that promote tumor cell proliferation and survival.
tyrosine kinases
Primary gastric GISTs usually form a , well-circumscribed, fleshy, submucosal mass
Metastases may form multiple small serosal nodules or fewer large nodules in the ; spread outside of the abdomen is uncommon.
solitary
liver
GISTs can be composed of thin, elongated cells or plumper
cells.
• is detectable in 95% of these tumors by IHC
spindle
epithelioid
KIT
What is the peak age of GIST?
More commone in males/females?
60, 10% @ 40
males
GISTs may come to clinical attention incidentally during work-up of other gastrointestinal symptoms, which are common.
GISTs may present with symptoms related to mass effects or mucosal ulceration, such as intestinal obstruction or gastrointestinal bleeding.
Small
Larger
note: ulcerated GIST
What is the primary treatment of localized gastric GIST?
complete surgical resection
The prognosis correlates with tumor size, mitotic index, and location, with gastric GISTs being somewhat more/less aggressive than those arising in the small intestine.*
less
GIST Tumors that are unresectable or metastatic often respond to tyrosine kinase inhibitors that are active against KIT and PDGFRA, such as
imatinib
From which cells do gastrointestinal stromal tumors arise (GISTS)?
benign pacemaker cells (interstitial cells of Cajal)
