Chapter 17: GIT- Gastric Polyps and Tumors Flashcards

Question

What is the most common malignancy of the stomach?

Answer 1

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

Answer 2

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.**

Answer 3

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.

Answer 4

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

Answer 5

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

Answer 6

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.

Answer 7

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]

Answer 8

While the majority of gastric cancers are not hereditary, the **mutations identified in familial gastric cancer**have 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.

Answer 9

**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

Answer 10

This implies an i**nteraction 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.

Answer 11

* **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**

Answer 12

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

Answer 13

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

Answer 14

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

Answer 15

* 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 ).

Answer 16

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 tumo**r.

Answer 17

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

Answer 18

**generally composed of discohesive cells** that **do not form glands** but **instead have large mucin vacuoles**that**expand 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.

Answer 19

mucin lakes

Answer 20

**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.

Answer 21

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.

Answer 22

**Breast and lung cancers**.

Answer 23

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.

Answer 24

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

Answer 25

**Intestinal-type gastric cancer**

Answer 26

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

Answer 27

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

Answer 28

**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

Answer 29

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]

Answer 30

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

Answer 31

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.

Answer 32

When possible, surgical resection . After surgical resection, the **5-year survival rate of early** gastric cancer **can exceed 90%,** **even if lymph node metastases**are 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%

Answer 33

GI tract, particularly the stomach.

Answer 34

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

Answer 35

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

Answer 36

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**.

Answer 37

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 lymphoma**s

Answer 38

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

Answer 39

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

Answer 40

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.

Answer 41

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.

Answer 42

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._***

Answer 43

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

Answer 44

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

Answer 45

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.

Answer 46

* 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 ).

Answer 47

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

Answer 48

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.

Answer 49

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

Answer 50

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.

Answer 51

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

Answer 52

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

Answer 53

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

Answer 54

* 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)**

Answer 55

* 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

Answer 56

* 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

Answer 57

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

Answer 58

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

Answer 59

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.

Answer 60

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.**

Answer 61

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**

Answer 62

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.

Answer 63

**sixth decade, but they may appear at any age.**

Answer 64

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**.

Answer 65

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.

Answer 66

* Foregut carcinoid tumors * Midgut carcinoid tumors * Hindgut carcinoids

Answer 67

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**

Answer 68

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.

Answer 69

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.

Answer 70

Overall, GISTs are **slightly more common in males.**

Answer 71

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

Answer 72

a nonhereditary syndrome seen **primarily in young female**s that **includes gastric GIST**, **paraganglioma, and pulmonary chondrom**a.

Answer 73

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

Answer 74

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

Answer 75

c-KIT and PDGFRA

Answer 76

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]

Answer 77

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.

Answer 78

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.

Answer 79

is c-KIT, which is immunohistochemically

Answer 80

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.

Answer 81

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.

Answer 82

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

Answer 83

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.