GI-Path-Neoplastic Diseases of the Stomach Flashcards

1
Q

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.

A

gastric polyps

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2
Q

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

A

epithelial

stromal

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3
Q

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

A

inflammatory or hyperplastic polyps.

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4
Q

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.
A

inflammation.

chronic

regress

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5
Q

What is happening in this slide?

A

hyperplasia

increased glands and stroma

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6
Q

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 >

A

size.

1.5 cm.

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7
Q

Describe the photo:

A

top: intestinal metaplasia with goblet cells in polyp

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

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8
Q

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

A

fundic gland polyps

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9
Q

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

A

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

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10
Q

Desribe the slide:

A

A: fundic gland polyps in stomach

B. fundic gland polyp

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

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11
Q

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

A

body

fundus

parietal

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12
Q

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

A

Gastric adenomas

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13
Q

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

A

age

atrophy

metaplasia.

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14
Q

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.*

A

dysplasia

size

2 cm

greater

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15
Q

What is noticed on this slide:

A

nuclear changes - larger nuclei, various shapes

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16
Q

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

A

Adenocarcinoma

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17
Q

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.

A

chronic

often

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18
Q

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.*

A

20

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19
Q

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

A

heterogeneous

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20
Q

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

A

E-cadherin

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21
Q

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

A

germ line mutations of CDH1

sporadic diffuse gastric tumors (methylation of CDH1 promotor)

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22
Q

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

A

diffuse

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23
Q

What is E-cadherin?

A

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

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

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24
Q

Loss of E-cadherin promotes tumor .

A

invasion

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25
Q

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

A

APC

intestinal-type

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26
Q

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?

A

sporadic intestinal-type gastric cancer (adenocarcinoma)

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27
Q

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

A

TP53

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28
Q

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

A

H. pylori infection

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29
Q

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?

A

interleukin-1β (IL-1β)

tumor necrosis factor (TNF).

30
Q

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

A

location

31
Q

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

A

Lauren

32
Q

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

A

Top: intestinal type

Middle and Bottom: diffuse type

33
Q

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.
A

intestinal-type gastric adenocarcinoma

34
Q

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.

A

diffuse gastric gastric adenocarcinoma

35
Q

Which type of gastric cancer displays a signet ring morphology?

A

diffuse gastric cancers (adenocarcinoma)

36
Q

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 .

A

linitis plastica

37
Q

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

A

Intestinal-type gastric cancer

38
Q

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?

A

diffuse gastric cancer

39
Q

What are the most powerful prognostic indicators for gastric cancer?

A

depth of invasion

extent of nodal metastasis

40
Q

Concerning gastric adenocarcinoma:

local invasion can occur in which 3 nearby structures?

A

duodenum

pancreas

retroperitoneum

41
Q

What is the preferred method of treatment of gastric adenocarcinoma?

A

surgical resection

42
Q

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

A

stomach.

B-cell

MALTomas.

note: diffuse infiltrates of lymphoma cells

43
Q

Describe the pathogenesis of Marginal Zone Lymphoma?

A

Chronic gastritis —> proliferation of polyclonal B cells

——-> Ag dependent polyclonal proliferation MALT lymphoma

————> Ag independent monoclonal MALT lymphoma

44
Q

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

A

antibiotics = polyclonal proliferation of B cells (B slide)

Chemo = Monoconal proliferation of B cells (C slide)

45
Q

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

A

carcinoid

endocrine pancreas

G cells

46
Q

Why are neuroendocrine tumors called “carcinoid”?

A

more slower growing

47
Q

Where are the most common places to find neuroendocrine tumors?

A

GI tract (40% in small intestine)

tracheobronchial tree

lungs

48
Q

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.

A

intramural (within the wall)

kinking

49
Q

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.

A

uniform

stippled

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

50
Q

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

A

sixth

51
Q

What produces the symptoms of carcinoid neuroendocrine tumors?

A

hormones

52
Q

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.

A

carcinoid syndrome

53
Q

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.

A

metabolized

strongly

54
Q

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

A

Foregut neuroendocrine (carcinoid) tumor

Midgut neuroendocrine (carcinoid) tumor

Hindgut neuroendocrine (carcinoid) tumor

55
Q

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.

A

Foregut neuroendocrine (carcinoid) tumor

56
Q

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?

A

gastrinomas

57
Q

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.

A

Midgut neuroendocrine (carcinoid) tumors

58
Q

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.*
A

Hindgut neuroendocrine (carcinoid) tumors

59
Q

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

A

Gastrointestinal stromal tumor (GIST)

note: the spindle shaped cells (mesenchymal in nature)

60
Q

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 ().

A

gain

KIT

PDGFRA

61
Q

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

A

gastrointestinal stromal tumor

62
Q

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.

A

tyrosine kinases

63
Q

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.

A

solitary

liver

64
Q

GISTs can be composed of thin, elongated cells or plumper

cells.

• is detectable in 95% of these tumors by IHC

A

spindle

epithelioid

KIT

65
Q

What is the peak age of GIST?

More commone in males/females?

A

60, 10% @ 40

males

66
Q

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.

A

Small

Larger

note: ulcerated GIST

67
Q

What is the primary treatment of localized gastric GIST?

A

complete surgical resection

68
Q

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.*

A

less

69
Q

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

A

imatinib

70
Q

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

A

benign pacemaker cells (interstitial cells of Cajal)

71
Q
A