Chapter 17: GIT- Gastric Polyps and Tumors

Question 1

What project above the level of the surrounding mucosa, are identified in up to 5% of upper GI endoscopies?

Answer 1

Polyps, nodules or masses

Question 2

What are polyps?

Answer 2

Polyps may develop as a result of epithelial or
stromal cell hyperplasia, inflammation,ectopia, or neoplasia.

Question 3

What are the common types of polyps?

Answer 3

Only the most common types of
polyps will be discussed here (Peutz-Jeghers and juvenile polyps are discussed with intestinal polyps).

This is followed by a presentation of gastric tumors, including adenocarcinomas,
lymphomas, carcinoid tumors, and stromal tumors.

Question 4

Approximately 75% of all gastric polyps are:

Answer 4

INFLAMMATORY AND HYPERPLASTIC POLYPS

Question 5

INFLAMMATORY AND HYPERPLASTIC POLYPS are most common in individuals of what age?

Answer 5

between 50 and 60 years of age.

Question 6

How do these polyps develop?

Answer 6

These polyps usually develop in association with chronic gastritis, which initiates the injury and reactive hyperplasia that leads to polyp growth.

Question 7

Among individuals with H. pylori gastritis, polyps may regress when?

Answer 7

after bacterial eradication

Question 8

Because the risk of dysplasia correlates with size, polyps larger than what should be resected and examined histologically?

Answer 8

1.5 cm

Question 9

Majority of inflammatory or hyperplastic polyps are what size?

Answer 9

smaller than 1 cm in diameter and are frequently multiple, particularly in individuals with atrophic gastritis.

Question 10

What are the characteristic in morphology of INFLAMMATORY AND HYPERPLASTIC POLYPS?

Answer 10

These polyps are ovoid in shape and have a smooth surface, though superficial erosions are common.

Microscopically, polyps have irregular, cystically dilated, and elongated foveolar glands ( Fig. 17-16A ).

The lamina propria is typically edematous with variable degrees of acute and chronic inflammation, and surface ulceration may be present ( Fig. 17-16B ).

Question 11

Answer 11

FIGURE 17-16 Gastric polyps.

• A, Hyperplastic polyp containing corkscrew-shaped foveolar glands.
• B, Hyperplastic polyp with ulceration.
• C, Fundic gland polyp composed of cystically dilated glands lined by parietal, chief, and foveolar cells.
• D, Gastric adenoma recognized by the presence of epithelial dysplasia

Question 12

Fundic gland polyps occur in individuals with what?

Answer 12

• sporadically and
• in individuals with familial adenomatous polyposis

(FAP).

Question 13

The prevalence of fundic gland polyps has increased markedly in recent years as a result of what?

Answer 13

proton pump inhibitor therapy.

This likely reflects increased gastrin secretion, in
response to reduced gastric acidity, and the resulting glandular hyperplasia.

Question 14

What gender and age is more affected by FUNDIC GLAND POLYPS?

Answer 14

These polyps are five times more common in women and are discovered at an average age of 50 years.

Question 15

What are the clinical features of Fundic
gland polyps?

Answer 15

• asymptomatic or
• rssociated
  
  • with nausea,
  • vomiting, or
  • epigastric pain.

Question 16

What is the morphology of Fundic gland polyps?

Answer 16

Morphology.

• occur in the gastric body and fundus
• and are wellcircumscribed
• lesions with a smooth surface.
• single or multiple
• and are composed of cystically dilated, irregular glands lined by flattened parietal and chief cells.
• Inflammation is typically absent or minimal ( Fig. 17-16C ).

Question 17

Gastric adenomas represent as many as how many percent of all gastric polyps?

Answer 17

10% of all gastric polyps ( Table 17-4 ).

Question 18

What is the incidence of GASTRIC ADENOMA?

Answer 18

increases progressively with age, [24] and there is a marked variation in rate among
different populationsthat parallels theincidence of gastric adenocarcinoma.

Question 19

What age are usually affected by GASTRIC ADENOMA?

Answer 19

Patients are
usually between 50 and 60 years of age, and males are affected three times more often than
females

Question 20

What is the incidence of GASTRIC ADENOMA?

.

Answer 20

Like fundic gland polyps, the incidence of adenomas is increased in individuals with
FAP.

Similar to other forms of gastric dysplasia, adenomas almost always occur on a
background of chronic gastritis with atrophy and intestinal metaplasia.

Question 21

The risk of
adenocarcinoma in gastric adenomas is related to the size of the lesion and is particularly
elevated in lesions of what size?

Answer 21

greater than 2 cm in diameter

Overall, carcinoma may be present in up to
30% of gastric adenomas. [24]

Question 22

Gastric adenomas are most commonly located were?

Answer 22

in the antrum

Question 23

What is the usual size of Gastric Adenoma?

Answer 23

are usually solitary lesions less than 2 cm in diameter,

Question 24

The majority of gastric adenomas are composed of what?

Answer 24

intestinal-type columnar epithelium.

By definition, all GI adenomas have epithelial dysplasia ( Fig. 17-16D ) that can be classified as low or high grade.

Both grades may include enlargement,
elongation, and hyperchromasia of epithelial cell nuclei, epithelial crowding, and pseudostratification.

High-grade dysplasia is characterized by more severe cytologic atypia and irregular architecture, including glandular budding and gland-within-gland, or cribriform, structures. [25]

Question 25

What is the most common malignancy of the stomach?

Answer 25

Adenocarcinoma is the most common malignancy of the stomach, comprising over 90% of all
gastric cancers.

Question 26

What are the early symptoms of GASTRIC ADENOCARCINOMA?

Answer 26

Early symptoms resemble those of chronic gastritis, including :

• dyspepsia
• , dysphagia, and
• nausea.

As a result, these tumors are often discovered at advanced stages,

when symptoms such as weight loss, anorexia, altered bowel habits, anemia, and hemorrhage
trigger further diagnostic evaluation.

Question 27

What is the epidemiology of Gastric Adenocarcinoma?

Answer 27

Gastric cancer incidence varies markedly with geography.

In Japan, Chile, Costa Rica, and
Eastern Europe the incidence is up to 20-fold higher than in North America, northern Europe,
Africa, and Southeast Asia.

Mass endoscopic screening programs can be successful in regions where the incidence is high, such as Japan, where 35% of newly detected cases are early
gastric cancer , tumors limited to the mucosa and submucosa. Unfortunately, mass screening
programs are not cost-effective in regions where the incidence is low, and fewer than 20% of
cases are detected at an early stage in North America and northern Europe.

Question 28

What is the cause of the overall reduction in gastric cancer?

Answer 28

The cause of the overall reduction in gastric cancer is unknown.

One possible explanation is
the decreased consumption of dietary carcinogens, such as N-nitroso compounds and benzo[a]pyrene, because of reduced use of salt and smoking for food preservation and the widespread availability of food refrigeration

. Conversely, intake of green, leafy vegetables and
citrus fruits, which contain antioxidants such as vitamin C, vitamin E, and beta-carotene,and is
correlated with reduced risk of gastric cancers, may have increased as a result of improved
food transportation networks

Question 29

Gastric cancer is more common in what group?

Answer 29

• lower socioeconomic groups and
• in individuals with multifocal mucosal atrophy
• and intestinal metaplasia.

Question 30

PUD impart an increased risk of gastric cancer.

T or F

Answer 30

FALSE

PUD does not impart an increased risk of gastric

cancer, but patients who have had partial gastrectomies for PUD have a slightly higher risk of
developing cancer in the residual gastric stump as a result of hypochlorhydria, bile reflux, and
chronic gastritis.

Question 31

Although overall incidence of gastric adenocarcinoma is falling, cancer of the gastric cardia is
on the rise.

What is the reason for this?

Answer 31

This is probably related to Barrett esophagus and may reflect the increasing
incidence of chronic GERD and obesity. [10]

Consistent with this presumed common
pathogenesis, distal esophageal adenocarcinomas and gastric cardia adenocarcinomas are
similar in morphology, clinical behavior, and therapeutic response. [27] [28] [29]

Question 32

What is the pathogenesis of GASTRIC ADENOCARCINOMA?

Answer 32

While the majority of gastric cancers are not hereditary, the mutations identified in familial
gastric cancerhave provided important insights into mechanisms of carcinogenesis in sporadic
cases.

Germline mutations in CDH1, which encodes E-cadherin, a protein that contributes to epithelial intercellular adhesion, are associated with familial gastric cancers, which are usually of the diffuse type.

Mutations in CDH1 are present in about 50% of sporadic cases of diffuse gastric tumors, while E-cadherin expression is drastically decreased in the rest, often by methylation of the CDH1 promoter.

Thus, the loss of E-cadherin function seems to be a key step in the development of diffuse gastric cancer .

Notably, CDH1 mutations are also common in
sporadic and familial lobular carcinoma of the breast, which also tends to infiltrate as single
cells, and individuals with BRCA2 mutations are at increased risk of developing diffuse gastric
cancer.

Question 33

What is the key step in the development of diffiuse gastric cancer?

Answer 33

loss of E-cadherin function

Germline mutations in CDH1, which encodes E-cadherin, a _protein that contributes to
epithelial intercellular adhesion_, are associated with familial gastric cancers, which are usually
of the diffuse type

Question 34

In contrast to diffuse gastric tumors, there is an increased risk of intestinal-type gastric cancer
in individuals with FAP, particularly in Japan.

What is the significance on its geographical predilection?

Answer 34

This implies an interaction between host genetic
background and environmental factors, since gastric cancer risk is less markedly elevated in individuals with FAP residing in areas of low gastric cancer incidence.

Question 35

What are the mutations described in sporadic intestinal-type gastric cancer?

Answer 35

• Mutations in β-catenin,
  
  • a protein that binds to both E-cadherin and adenomatous polyposis coli (APC), as well as microsatellite instability and
• hypermethylation of several genes including:
  
  • TGFβRII,
  • BAX,
  • IGFRII, and
  • p16/INK4a have also been described in sporadic intestinal-type gastric cancer

Question 36

What are the genetic variants that are associated with elevated risk of gastric cancer when accompanied by H. pylori infection, and p53 mutations are present in the majority of sporadic gastric cancers of both histologic types

Answer 36

Genetic variants of pro-inflammatory and immune response genes, including those that encode:

• IL-1β,
• TNF,
• IL-10,
• IL-8, and
• Toll-like receptor 4 (TLR4), .

Thus, although specific sequences

of events have not been defined, it is clear that chronic inflammation promotes neoplastic
progression. Other associations between chronic inflammation and cancer were discussed in
Chapter 7

Question 37

Gastric adenocarcinomas are classified according to their what?

Answer 37

location in the stomach, and most importantly, according to gross and histologic morphology

Question 38

Most gastric adenocarcinomas involve the what?

Answer 38

gastric antrum; the lesser curvature is involved more often than the greater curvature.

Question 39

What is the difference between gastric tumors with intestinal morphology compared to a diffurse infilttative grwoth pattern?

Answer 39

• intestinal morphology tend to form bulky tumors ( Fig. 17-17A ) composed of glandular structures ( Fig. 17-18A ),
• diffuse infiltrative growth pattern (see Fig. 17-17B ) are more often composed of signet-ring cells (see Fig. 17-18B ).

Question 40

Where do gastric carcinomas typically grow?

Answer 40

Although intestinal-type adenocarcinomas may penetrate the gastric wall, they typically grow along broad cohesive fronts to form either an
exophytic mass or an ulcerated tumor.

Question 41

What is the compostiiton of intestinal-type adenocarcinomas?

Answer 41

The neoplastic cells often contain apical mucin
vacuoles, and abundant mucin may be present in gland lumens

Question 42

What is the composition of diffuse gastric cancer?

Answer 42

generally composed of discohesive cells that do not form glands but instead have
large mucin vacuolesthatexpand the cytoplasm and push the nucleus to the periphery,
creating a signet-ring cell morphology.

These cells permeate the mucosa and stomach wall
individually or in small clusters, which makes tumor cells easy to confuse with inflammatory
cells, such as macrophages, at low magnification.

Question 43

Extracellular mucin release in either type
of gastric cancer can result in formation of large ________that dissect tissue planes

Answer 43

mucin lakes

Question 44

A mass may be difficult to appreciate in diffuse gastric cancer, but these infiltrative tumors
often evoke what reaction?

Answer 44

desmoplastic reaction that stiffens the gastric wall and may provide a
valuable diagnostic clue.

When there are large areas of infitration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastica
(see Fig. 17-17B ). Breast and lung cancers that metastasize to the stomach may also
create a linitis plastica–like appearance.

Question 45

What is linitis plastica?

Answer 45

When there are large areas of infitration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastica
(see Fig. 17-17B ).

Breast and lung cancers that metastasize to the stomach may also create a linitis plastica–like appearance.

Question 46

What metastatic cancers may also create a linitis plastica–like appearance?

Answer 46

Breast and lung cancers.

Question 47

Answer 47

FIGURE 17-17 Gastric adenocarcinoma.

• A, Intestinal-type adenocarcinoma consisting of an elevated mass with heaped-up borders and central ulceration. Compare to the peptic ulcer in Figure 17-14A
• . B, Linitis plastica. The gastric wall is markedly thickened, and rugal folds are partially lost.

Question 48

Answer 48

FIGURE 17-18 Gastric adenocarcinoma.

• A, Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through desmoplastic stroma.
• B, Signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent-shaped nuclei

Question 49

In gastric adenocarcinoma what predominates in high rish area and develops from precusor lesions including dysplasia and adenomas?

Answer 49

Intestinal-type gastric cancer

Question 50

WHat is the mean age of presentation in Inestinal type gastric adenocarcinoma?

Answer 50

The mean age of presentation is 55 years, and
the male-to-female ratio is 2 : 1.

Question 51

What is the incidence of diffuse gastric cancer

Answer 51

uniform across countries, there are no identified precursor lesions, and the disease occurs at similar frequencies in males and females.

Question 52

Notably, the remarkable decrease in gastric cancer
incidence applies only to the what?

Answer 52

intestinal type, which is most closely associated with atrophic gastritis and intestinal metaplasia.

As a result, the incidences of intestinal and diffuse types of
gastric cancers are now similar

Question 53

What are the most powerful prognostic indicators for gastric cancer?

Answer 53

The depth of invasion and the extent of nodal and distant metastasis at the time of diagnosis
remain the most powerful prognostic indicators for gastric cancer . [30]

Question 54

In advanced cases
gastric carcinoma may first be detected as metastases where?

Answer 54

to the supraclavicular sentinel lymph node, also called Virchow’s node.

Question 55

Gastric tumors can also metastasize to where?

Answer 55

periumbilical region to form a subcutaneous nodule, termed a Sister Mary Joseph nodule , after the nurse
who first noted this lesion as a marker of metastatic carcinoma.

Local invasion into the
duodenum, pancreas, and retroperitoneum is also characteristic. In such cases efforts are
usually focused on chemotherapy or radiation therapy and palliative care.

Question 56

What remains the preferred treatment for gastric adenocarcinoma?

Answer 56

When possible, surgical resection .

After surgical resection, the 5-year survival rate of early gastric cancer can exceed 90%, even if
lymph node metastasesare present.

In contrast, the 5-year survival rate for advanced gastric cancer remains below 20%. [28]

Because of the advanced stage at which most gastric cancers are discovered in the United States, the overall 5-year survival is less than 30%

Question 57

Although extra-nodal lymphomas can arise in virtually any tissue, they do so most commonly in
the where?

Answer 57

GI tract, particularly the stomach.

Question 58

In allogeneic bone marrow transplant and organ
transplant recipients, the bowel is also the most frequent site for Epstein-Barr virus–positive Bcell
lymphoproliferations, why?

Answer 58

because the **deficits in T-cell function** caused by oral
immunosuppressive agents (e.g., cyclosporine) are greatest at intestinal sites of drug
absorption.

Question 59

Nearly 5% of all gastric malignancies are primary lymphomas,

Answer 59

the most common of
which are indolent extra-nodal marginal zone B-cell lymphomas.

In the gut these tumors are
often referred to as lymphomas of mucosa-associated lymphoid tissue (MALT) , or
MALTomas. [33]

This entity and the second most common primary lymphoma of the gut, diffuse
large B-cell lymphoma, are also discussed in Chapter 13

Question 60

Extra-nodal marginal zone B-cell lymphomas usually arise at sites of what?

Answer 60

chronic inflammation

They can originate in the GI tract at sites of preexisting MALT, such as the Peyer’s patches of the
small intestine, but more commonly arise within tissues that are normally devoid of organized
lymphoid tissue.

Question 61

What is The most common cause of “pro-lymphomatous” inflammation in the stomach?

Answer 61

chronic H. pylori infection, which is found in association with most cases of gastric
MALToma. [34]

As with other low-grade lymphomas, MALTomas can transform into more aggressive tumors that are histologically identical to diffuse large B-cell lymphomas

Question 62

What is the most striking evidence linking H. pylori gastritis to MALToma?

Answer 62

is that eradication of the infection with antibiotics induces durable remissions with low rates of recurrence in most patients. [35]

Histologic features that predict antibiotic treatment failures include transformation
to large-cell lymphoma, tumor invasion to the muscularis propria or beyond, and lymph node
involvemenent

Question 63

What is theHistologic features that predict antibiotic treatment failures ?

Answer 63

• transformation to large-cell lymphoma
• tumor invasion to the muscularis propria or beyond, and
• lymph node involvemenent

Question 64

What are the three translocations are associated with gastric MALToma,

Answer 64

1. the t(11;18)(q21;q21) and
2. the less common t(1;14)(p22;q32) and
3. t(14;18)(q32;q21).

They are also highly predictive of response

failure. [36,] [37]

The t(11;18)(q21;q21) translocation brings together the apoptosis inhibitor 2
(API2) gene on chromosome 11 with the “mutated in MALT lymphoma,” or MLT , gene on
chromosome 18.

This creates a chimeric API2-MLT fusion gene that encodes an API2-MLT
fusion protein.

The t(14;18)(q32;q21) and t(1;14)(p22;q32) translocations cause increased expression of intact MLT and BCL-10 proteins, respectively.

Although some details remain uncertain, each of the three translocations has the same net
effect, the constitutive activation of NF-κB, a transcription factor that promotes B-cell growth
and survival.

Remarkably, antigen-dependent activation of NF-κB in normal B and T cells
requires both BCL-10 and MLT, which work together in a pathway down-stream of the B- and TGastric cell antigen receptors.

Question 65

In MALTomas that lack these translocations, what is the pathogenesis?

Answer 65

H. pylori–induced inflammation may trigger NF-κB activation through the MLT/BCL-10 pathway. In these tumors elimination of the immune stimulus (H. pylori) down-regulates NF-κB, resulting in tumor
regression.

In contrast, NF-κB is constitutively active in tumors bearing translocations involving
MLT or BCL10, and as a result the elimination of H. pylori has no effect.

Additional genetic
changes, such as inactivation of the tumor suppressor genes that encode p53 and p16, may
lead to transformation of gastric MALToma into aggressive diffuse large B-cell lymphoma.

Question 66

Histologically, gastric MALToma takes the form of a what?

Answer 66

dense lymphocytic infiltrate in the lamina propria ( Fig. 17-19A ).

Characteristically, the neoplastic lymphocytes infiltrate
the gastric glands focally to create diagnostic lymphoepithelial lesions ( Fig. 17-19A , inset).

Reactive-appearing B-cell follicles may be present, and, in about 40% of tumors, plasmacytic differentiation is observed.

Occasionally the tumor cells accumulate large
amounts of pale cytoplasm, a feature referred to as “monocytoid” change.

Question 67

Like other tumors of mature B cells, MALTomas express what markers?

Answer 67

the B-cell markers CD19 and CD20.
They do not express CD5 and CD10, and are positive for CD43 in about 25% of cases, an unusual feature that can be diagnostically helpful.

In cases lacking lymphoepithelial lesions,
monoclonality may be demonstrated by restricted expression of either κ or γ immunoglobulin
light chain or by molecular detection of clonal IgH rearrangements.

Molecular cytogenetic
analysis (e.g., fluorescent in situ hybridization) is being used increasingly to identify tumors
with translocations that predict resistance to therapy

Question 68

What is the unusual feature of MALTOMas that can be diagnostically helpful?

Answer 68

positive for CD43 in about 25% of cases, an unusual feature that can be diagnostically helpful.

Question 69

Answer 69

FIGURE 17-19 GI lymphoma.

• A, Gastric MALT lymphoma replacing much of the gastric epithelium. Inset shows lymphoepithelial lesions with neoplastic lymphocytes surrounding and infiltrating gastric glands.
• B, Disseminated lymphoma within the small intestine with numerous small serosal nodules.
• C, Large B-cell lymphoma infiltrating the small intestinal wall and producing diffuse thickening.

Question 70

What is the most common presenting symtoms of MALTomas?

Answer 70

• The most common presenting symptoms are dyspepsia and epigastric pain.
• Hematemesis, melena, and constitutional symptoms such as weight loss can also be present.

Because gastric
MALTomas and H. pylori gastritis often coexist and have overlapping clinical symptoms and
endoscopic appearances, diagnostic difficulties sometimes arise, particularly in small biopsy
specimens. GI lymphomas may also disseminate as discrete small nodules ( Fig. 17-19B ) or
infiltrate the wall diffusely ( Fig. 17-19C ).

Question 71

Where does Carciinoid tumors arise?

Answer 71

Carcinoid tumors arise from the diffuse components of the endocrine system.

Question 72

The majority of Carcinoid tumors are
found where?

Answer 72

in the GI tract, and more than 40% occur in the small intestine ( Table 17-5 ). [39]

The tracheobronchial tree and lungs are the next most commonly sites involved.

Question 73

Gastric carcinoids may be associated with what?

Answer 73

• endocrine cell hyperplasia,
• chronic atrophic gastritis, and
• Zollinger- Ellison syndrome.

Question 74

What is does carcinoid tumors mean?

Answer 74

The term carcinoid, or “carcinoma-like,” was applied because these tumors tend to have a more indolent clinical course than GI carcinomas.

Carcinoid tumors are best
considered to be well-differentiated neuroendocrine carcinomas.

Carcinoids within the GI tract
arise from the endocrine cells that release peptide and nonpeptide hormones to coordinate gut
function.

Question 75

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Fraction of
GI
carcinoids

Answer 75

• Esophagus : <1%
• Stomach: <10%
• Proximal Duodenum: <10%
• Jejunum and Ileum : >40%
• Appendix : <25%
• Colorectum :>25%

Question 76

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Mean
patient age
(yr)

Answer 76

• Esophagus : Rare
• Stomach: 55
• Proximal Duodenum: 50
• Jejunum and Ileum :65
• Appendix :All ages
• Colorectum :60

Question 77

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Location

Answer 77

• Esophagus :Distal
• Stomach: Body and fundus
• Proximal Duodenum: Proximal third, peri-ampullary
• Jejunum and Ileum :Throughout
• Appendix :Tip
• Colorectum :Rectum >
  cecum

Question 78

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Size

Answer 78

• Esophagus :Limited data
• Stomach: 1–2 cm, multiple; >2 cm, solitary
• Proximal Duodenum: 0.5–2 cm
• Jejunum and Ileum :<3.5 cm
• Appendix :0.2–1 cm
• Colorectum : >5 cm (cecum); <1 cm (rectum)

Question 79

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Secretory
product(s)

Answer 79

• Esophagus :Limited data
• Stomach: Histamine, somatostatin, serotonin
• Proximal Duodenum: Gastrin, somatostatin, cholecystokinin
• Jejunum and Ileum : Serotonin, substance P, polypeptide YY
• Appendix :Serotonin, polypeptide YY
• Colorectum : Serotonin, polypeptide YY

Question 80

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Symptoms

Answer 80

• Esophagus:
  
  • Dysphagia,
  • weight loss,
  • reflux
• Stomach:
  
  • Gastritis,
  • ulcer,
  • incidental
• Proximal Duodenum:
  
  • Peptic ulcer,
  • biliary obstruction
  • abdominal pain
• Jejunum and Ileum :
  
  • Asymptomatic,
  • obstruction,
  • metastatic disease
• Appendix
  
  • :Asymptomatic,
  • incidental
• Colorectum :
  
  • Abdominal pain,
  • weight loss,
  • incidental

Question 81

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Behavior

Answer 81

• Esophagus :Limited data
• Stomach: Variable
• Proximal Duodenum : Variable
• Jejunum and Ileum : Aggressive
• Appendix : Benign
• Colorectum : Variable

Question 82

TABLE 17-5 – Features of Gastrointestinal Carcinoid Tumors

Disease associations

Answer 82

• Esophagus :None
• Stomach: Atrophic gastritis, MEN-I
• Proximal Duodenum :Zollinger- Ellison syndrome, NF- 1, sporadic
• Jejunum and Ileum :None
• Appendix : None
• Colorectum : None

Question 83

What is the gross appearance of carcinoids?

Answer 83

Grossly, carcinoids are intramural or submucosal masses that create small polypoid lesions ( Fig. 17-20A ).

The overlying mucosa may be intact or ulcerated, and the tumors may invade deeply to involve the mesentery.

Question 84

What is the color of carcinoid?

Answer 84

Carcinoids tend to be yellow or tan in
color and are very firm as a consequence of an intense desmoplastic reaction, which may
cause kinking of the bowel and obstruction.

Question 85

What is the appearance of carcinoid tumors histologically?

Answer 85

Histologically, carcinoid tumors are composed of
islands, trabeculae, strands, glands, or sheets of uniform cells with scant, pink granular
cytoplasm and a round to oval stippled nucleus ( Fig. 17-20 ).

In most tumors there is minimal
pleomorphism, but anaplasia, mitotic activity, and necrosis may be present in rare cases.
Immunohistochemical stains are typically positive for endocrine granule markers, such as
synaptophysin and chromogranin A

Question 86

Answer 86

FIGURE 17-20 GI carcinoid tumor (neuroendocrine carcinoma).

• A, Gross cross-section of a submucosal tumor nodule.
• B, Microscopically the nodule is composed of tumor cells embedded in dense fibrous tissue.
• C, In other areas, the tumor has spread extensively within mucosal lymphatic channels.
• D, High magnification shows the bland cytology of carcinoid tumors. The chromatin texture, with fine and coarse clumps, is frequently described as a “salt and pepper” pattern. Despite their innocuous appearance, carcinoids can be extremely aggressive clinically.
• E, Electron microscopy reveals cytoplasmic dense
• core neurosecretory granules.

Question 87

What is the peak incidence of carcinoid tumors?

Answer 87

sixth decade, but they may appear at any age.

Question 88

What are the symptoms of Carcinoid Tumors?

Answer 88

Symptoms are determined by the hormones produced.

• For example, tumors that produce gastrin may cause Zollinger-Ellison syndrome,
• while ileal tumors may cause carcinoid syndrome, which is characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis.

Question 89

Carcinoid syndrome occurs in fewer than 10% of patients and is caused by what?

Answer 89

vasoactive substances secreted by the tumor into the systemic circulation.

When tumors are confined to the intestine, the vasoactive substances released are metabolized to inactive forms by the liver, a “first-pass” effect similar to that exerted on oral drugs.

Carcinoid syndrome generally requires tumors to secrete hormones into a non-portal venous circulation and therefore is strongly associated with metastatic
disease.

Question 90

The most important prognostic factor for GI carcinoid tumors is location

Answer 90

• Foregut carcinoid tumors
• Midgut carcinoid tumors
• Hindgut carcinoids

Question 91

What are foregut carcinoid tumors?

Answer 91

Foregut carcinoid tumors, those found within the stomach, duodenum proximal to the ligament of Treitz, and esophagus, rarely metastasize and are generally cured by resection.

This is particularly true for gastric carcinoid tumors that arise in association with atrophic gastritis, while gastric carcinoid tumors without predisposing factors are
more aggressive

Question 92

What are midgut carcinoid tumors?

Answer 92

Midgut carcinoid tumors that arise in the jejunum and ileum are often multiple and tend to be aggressive.

In these tumors, greater depth of local invasion, increased size, and presence of necrosis and mitosis are associated with poor outcome.

Question 93

Where do hindgut carcinoids arise?

Answer 93

Hindgut carcinoids arising in the appendix and colorectum are typically discovered incidentally.

Those in the appendix occur at any age and are generally located at the tip.
These tumors are rarely more than 2 cm in diameter and are almost uniformly benign.

Rectal carcinoid tumors tend to produce polypeptide hormones and, when symptomatic,
present with abdominal pain and weight loss.

Metastasis of rectal carcinoid tumors is
uncommon. In contrast, tumors of the proximal colon are uncommon but may grow to
large size and metastasize.

Question 94

A wide variety of mesenchymal neoplasms may arise in the stomach.

Many are named according to the cell type they most resemble; for example, smooth muscle tumors are called leiomyomas or leiomyosarcomas, nerve sheath tumors are termed schwannomas, and those resembling glomus bodies in the nailbeds and at other sites are termed glomus tumors.

These
are all rare and are discussed in greater detail in Chapter 26 . GI stromal tumor (GIST) is the
most common mesenchymal tumor of the abdomen, and more than half of these tumors occur
in the stomach. As will be discussed below, the term stromal reflects historical confusion about
the origin of this tumor

Question 95

What is the epidemiology of GISTs?

Answer 95

Overall, GISTs are slightly more common in males.

Question 96

What is the peak age of GIST diagnosis in the
stomach?

Answer 96

approximately 60 years, with fewer than 10% occurring in individuals under 40 years of age.

Question 97

Of the uncommon GISTs in children, some are related to the Carney triad , what is this triad?

Answer 97

a nonhereditary syndrome seen primarily in young females that includes gastric GIST,
paraganglioma, and pulmonary chondroma.

Question 98

There is also an increased incidence of GIST in
individuals with neurofibromatosis type 1. [40]

Question 99

Approximately 75% to 80% of all GISTs have oncogenic, gain-of-function mutations of which gene?

Answer 99

gene
encoding the tyrosine kinase c-KIT , which is the receptor for stem cell factor.

Question 100

Approximately 8%
of GISTs have mutations that activate a related what? [41]

Answer 100

tyrosine kinase, platelet-derived growth factor
receptor α (PDGFRA).

Question 101

In sporadic GISTs, what gene mutations are mutually exclusive. [21]

Answer 101

c-KIT and PDGFRA

Question 102

GISTs appear to arise from, or share a common stem cell with, what?

Answer 102

the interstitial cells of Cajal, which are located in the muscularis propria and serve as pacemaker cells for gut peristalsis.

Like GISTs, Cajal cells express c-KIT (also known as CD117) and CD34.
Interestingly, familial GIST, which is rare, is associated with germline c-KIT or PDGFRA mutations; these patients, who develop multiple GISTs, may also have diffuse hyperplasia of Cajal cells. [42]

Mutation of c-KIT or PDGFRA is an early event in sporadic GISTs and is detectable in lesions as small as 3 mm.

The constitutively active c-KIT and PDGFRA receptor
tyrosine kinases produce intracellular signals that activate the RAS and PI3K/AKT pathways
and thereby promote tumor cell proliferation and survival. [21]

Question 103

What are is the size of Primary gastriic GISTs?

Answer 103

Primary gastric GISTs can be quite large, as much as 30 cm in diameter.

They usually form a solitary, well-circumscribed, fleshy mass ( Fig. 17-21A ) covered by ulcerated or intact mucosa ( Fig. 17-21B ), but can also project outward toward the serosa.

Metastases may take the form of multiple serosal nodules throughout the peritoneal cavity or as one or
more nodules in the liver; spread outside of the abdomen is uncommon.

Question 104

GISTs are composed of what

Answer 104

GISTs composed of thin elongated cells are classified as spindle cell type ( Fig. 17-21C ), whereas tumors
dominated by epithelial-appearing cells are termed epithelioid type; mixtures of the two patterns also occur.

Question 105

What is The most useful diagnostic marke rdetectable in 95% of gastric GISTs?

Answer 105

is c-KIT, which is
immunohistochemically

Question 106

Answer 106

FIGURE 17-21 GI stromal tumor.

• A, On cross-section a whorled texture is evident within the white, fleshy tumor.
• B, The mass is covered by intact mucosa.
• C, Histologically the
• tumor is primarily composed of bundles, or fascicles, of spindle-shaped tumor cells.

Question 107

What are the symptoms of GISTs?

Answer 107

Symptoms of GISTs at presentation may be related to mass effects.

Mucosal ulceration can cause blood loss, and approximately half of individuals with GIST present with anemia or related symptoms.

GISTs may also be discovered as an incidental finding during radiologic imaging, endoscopy, or abdominal surgery performed for other reasons.

Question 108

What is the primary treatment for localized gastric GIST?

Answer 108

Complete surgical resection is the primary treatment for localized gastric GIST.

Question 109

What is the prognosis of GIST?

Answer 109

The prognosis correlates with tumor size,
mitotic index, and location, with gastric GISTs being somewhat less aggressive than those arising in the small intestine.

Recurrence or metastasis is rare for gastric GISTs under 5 cm but
common for mitotically active tumors larger than 10 cm.