GI-Path-Neoplastic Diseases of the Stomach

Question 1

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.

Answer 1

gastric polyps

Question 2

Polyps may develop as a result of or cell hyperplasia, inflammation, ectopia (congentital abnormal position), or neoplasia

Answer 2

epithelial

stromal

Question 3

Up to 75% of all gastric polyps are what 2 kinds of gastric polyps?

Answer 3

inflammatory or hyperplastic polyps.

Question 4

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.

Answer 4

inflammation.

chronic

regress

Question 5

What is happening in this slide?

Answer 5

hyperplasia

increased glands and stroma

Question 6

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 >

Answer 6

size.

1.5 cm.

Question 7

Describe the photo:

Answer 7

top: intestinal metaplasia with goblet cells in polyp

bottom: High-grade dysplasia in a gastric hyperplastic polyp.

Question 8

What type of polyp occur sporadically and in individuals with familial adenomatous polyposis (FAP).?

Answer 8

fundic gland polyps

Question 9

Why has the incidence of sporadic fundic gland polyps lesions increased?

Answer 9

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

Question 10

Desribe the slide:

Answer 10

A: fundic gland polyps in stomach

B. fundic gland polyp

C: fundic gland polyp with parietal (a, pink) and chief cells (purple)

Question 11

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

Answer 11

body

fundus

parietal

Question 12

What type of polyp represent up to 10% of all gastric polyps?

Answer 12

Gastric adenomas

Question 13

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

Answer 13

age

atrophy

metaplasia.

Question 14

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.*

Answer 14

dysplasia

size

2 cm

greater

Question 15

What is noticed on this slide:

Answer 15

nuclear changes - larger nuclei, various shapes

Question 16

What is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers?

Answer 16

Adenocarcinoma

Question 17

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.

Answer 17

chronic

often

Question 18

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.*

Answer 18

20

Question 19

Gastric cancers are genetically heterogeneous/homogenous, but certain molecular alterations are common.

Answer 19

heterogeneous

Question 20

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

Answer 20

E-cadherin

Question 21

CDH1 mutations that result in loss of E-cadherin can develop in which 2 ways?

Answer 21

germ line mutations of CDH1

sporadic diffuse gastric tumors (methylation of CDH1 promotor)

Question 22

Thus, the loss of E-cadherin function seems to be a key step in the development of gastric cancer, whether germ line or sporadic.

Answer 22

diffuse

Question 23

What is E-cadherin?

Answer 23

a protein that contributes to epithelial intercellular adhesion (zonula adherens)

(associated with familial gastric cancers, usually of the diffuse type).

Question 24

Loss of E-cadherin promotes tumor .

Answer 24

invasion

Question 25

Patients with familial adenomatous polyposis who have germ line mutations in genes have an increased risk for development of gastric cancer.

Answer 25

APC intestinal-type

Question 26

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?**

Answer 26

sporadic intestinal-type gastric cancer (adenocarcinoma)

Question 27

mutations are present in a majority of sporadic gastric cancers of both histologic types (intestinal-type and diffuse)

Answer 27

TP53

Question 28

Chronic gastritis, most commonly due to ,\* promotes the development and progression of cancers that may be induced by diverse genetic alterations.

Answer 28

H. pylori infection

Question 29

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?

Answer 29

interleukin-1β (IL-1β) tumor necrosis factor (TNF).

Question 30

Gastric adenocarcinomas are classified according to their in the stomach as well as gross and histologic morphology

Answer 30

location

Question 31

The classification that separates gastric cancers into **intestinal and diffuse types** correlates with the distinct patterns of molecular alterations .

Answer 31

Lauren

Question 32

Describe the drawing? What do each of the stomachs represent?

Answer 32

Top: intestinal type Middle and Bottom: diffuse type

Question 33

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.

Answer 33

intestinal-type gastric adenocarcinoma

Question 34

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.

Answer 34

diffuse gastric gastric adenocarcinoma

Question 35

Which type of gastric cancer displays a signet ring morphology?

Answer 35

diffuse gastric cancers (adenocarcinoma)

Question 36

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 _._

Answer 36

linitis plastica

Question 37

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

Answer 37

Intestinal-type gastric cancer

Question 38

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?

Answer 38

diffuse gastric cancer

Question 39

What are the most powerful prognostic indicators for gastric cancer?

Answer 39

depth of invasion extent of nodal metastasis

Question 40

Concerning gastric adenocarcinoma: local invasion can occur in which 3 nearby structures?

Answer 40

duodenum pancreas retroperitoneum

Question 41

What is the preferred method of treatment of gastric adenocarcinoma?

Answer 41

surgical resection

Question 42

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

Answer 42

stomach. B-cell MALTomas. **note: diffuse infiltrates of lymphoma cells**

Question 43

Describe the pathogenesis of Marginal Zone Lymphoma?

Answer 43

Chronic gastritis ---\> proliferation of polyclonal B cells -------\> Ag dependent polyclonal proliferation MALT lymphoma ------------\> Ag independent monoclonal MALT lymphoma

Question 44

At which stage of MALT lymphoma pathogenesis are antibiotics an appropriate treatement and chemotherapy an appropriate treatment?

Answer 44

antibiotics = polyclonal proliferation of B cells (B slide) Chemo = Monoconal proliferation of B cells (C slide)

Question 45

Neuroendocrine tumors, also referred to as tumors, arise from neuroendocrine organs (eg, the ) and neuroendocrine-differentiated GI epithelia (eg, ).

Answer 45

carcinoid endocrine pancreas G cells

Question 46

Why are neuroendocrine tumors called "carcinoid"?

Answer 46

more slower growing

Question 47

Where are the most common places to find neuroendocrine tumors?

Answer 47

GI tract (40% in small intestine) tracheobronchial tree lungs

Question 48

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.

Answer 48

intramural (within the wall) kinking

Question 49

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.

Answer 49

uniform stippled **note: on the left is pink fibrosis, right are stippled uniform nuclei**

Question 50

The peak incidence of neuroendocrine tumors is in the decade, but they may appear at any age.

Answer 50

sixth

Question 51

What produces the symptoms of carcinoid neuroendocrine tumors?

Answer 51

hormones

Question 52

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.**

Answer 52

carcinoid syndrome

Question 53

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.

Answer 53

metabolized strongly

Question 54

What are the 3 different subtypes of neurodendocrine (carcinoid) tumors?

Answer 54

Foregut neuroendocrine (carcinoid) tumor Midgut neuroendocrine (carcinoid) tumor Hindgut neuroendocrine (carcinoid) tumor

Question 55

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.

Answer 55

Foregut neuroendocrine (carcinoid) tumor

Question 56

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**?

Answer 56

gastrinomas

Question 57

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.

Answer 57

Midgut neuroendocrine (carcinoid) tumors

Question 58

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.\***

Answer 58

Hindgut neuroendocrine (carcinoid) tumors

Question 59

What is the most common mesenchymal tumor of the abdomen, and more than half of these tumors occur in the stomach?

Answer 59

Gastrointestinal stromal tumor (GIST) note: the spindle shaped cells (mesenchymal in nature)

Question 60

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 ().

Answer 60

gain KIT PDGFRA

Question 61

Which gastrointestinal tumor is associated with mutations of KIT (receptor of stem cell factor) and PDGFRA (platelet derived growth factor receptor)?

Answer 61

gastrointestinal stromal tumor

Question 62

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.

Answer 62

tyrosine kinases

Question 63

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.

Answer 63

solitary liver

Question 64

GISTs can be composed of thin, elongated cells or plumper cells. • is detectable in 95% of these tumors by IHC

Answer 64

spindle epithelioid KIT

Question 65

What is the peak age of GIST? More commone in males/females?

Answer 65

60, 10% @ 40 males

Question 66

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.**

Answer 66

Small Larger note: ulcerated GIST

Question 67

What is the primary treatment of localized gastric GIST?

Answer 67

complete surgical resection

Question 68

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.\*

Answer 68

less

Question 69

GIST Tumors that are unresectable or metastatic often respond to tyrosine kinase inhibitors that are active against KIT and PDGFRA, such as

Answer 69

imatinib

Question 70

From which cells do gastrointestinal stromal tumors arise (GISTS)?

Answer 70

benign pacemaker cells (interstitial cells of Cajal)