The small intestine represents 75% of the length and 90% of the surface area of the gastrointestinal tract, yet neoplasms of the small intestine are rare, accounting for only 1% to 2% of all gastrointestinal neoplasms and less than 1% of all cancers in the United States. Four major types of primary neoplasms arise in the small intestine. They are, in order of descending frequency, adenocarcinomas, carcinoid tumors, lymphomas, and sarcomas. The small intestine is also the most common tubular gastrointestinal site for involvement by secondary tumors, which are more than twice as common as primary small intestinal tumors. In this chapter, we discuss primary adenocarcinomas, carcinoids, and common secondary tumors of the small intestine. Lymphomas and sarcomas are discussed elsewhere.
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Adenocarcinomas of the small intestine
Clinical features
Adenocarcinomas are the most common primary malignancies of the small intestine, comprising from 30% to 50% of all small bowel malignancies. Primary adenocarcinomas are still rare lesions, however, and account for only 2% of gastrointestinal tract tumors and 1% of all gastrointestinal tract cancer deaths. They present in older adults (median 67 years), with a male predominance, and are more common in African-Americans than whites. Like colorectal adenocarcinomas, the vast majority of small intestinal adenocarcinomas are sporadic and arise from adenomatous polyps. Risk factors for small intestinal adenocarcinoma are similar to those for colorectal adenocarcinoma, and their incidence rates correlate highly worldwide. Risk factors for sporadic adenocarcinoma reportedly include smoking and consumption of alcohol, red meat, and fats. Increased body mass index may also be a risk factor. The remaining adenocarcinomas arise in the background of certain predisposing conditions, including certain polyposis syndromes, Crohn’s disease, gluten-sensitive enteropathy (GSE), ileostomy, and ileal conduit. Familial adenomatous polyposis (FAP) carries the greatest increase in risk for small intestinal adenocarcinoma (100- to 200-fold), followed by Crohn’s disease and GSE, each of which is increased 80-fold. Other polyposis syndromes with increased risk include hereditary nonpolyposis colon cancer syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome.
The majority of small intestinal adenomas are located in the duodenum, and, like their colonic counterparts, exhibit three major histologic types: tubular, tubulovillous, and villous ( Fig. 6-1 ). Most adenomas occur singly, and the presence of multiple adenomas in the small intestine is unusual in the absence of FAP. Because of their potential to undergo malignant transformation, adenomas should be removed. Endoscopic polypectomy is appropriated for pedunculated tumors, while large sessile lesions require endoscopic mucosal resection or surgical resection.
Adenocarcinomas arising sporadically and in the setting of most predisposing conditions occur most frequently in the duodenum, where 65% are periampullary. The incidence decreases progressively through the rest of the small intestine. Adenocarcinoma arising in Crohn’s disease is a notable exception to this rule. In Crohn’s disease, 70% of adenocarcinomas are found in the ileum, the primary site of the inflammatory process ( Figs. 6-2 and 6-3 ).
The most common presenting symptoms of small intestinal adenocarcinoma are abdominal pain, obstruction, and occult gastrointestinal bleeding. Patients with duodenal adenocarcinomas may present with gastric outlet obstruction, while the combination of obstructive jaundice with occult gastrointestinal bleeding is characteristic of ampullary tumors. More distal lesions tend to result in severe, cramping abdominal pain. Intestinal obstruction can be caused by progression of an apple core lesion or by a large intraluminal polypoid mass. Distal adenocarcinomas tend to present with advanced disease (stage III or IV).
Duodenal lesions can typically be detected on routine endoscopy, whereas more distal lesions may require push or capsule enteroscopy, intraoperative endoscopy, or radiographic imaging modalities. Endoscopic ultrasound (EUS) may be of use to assess depth of invasion and local lymph node metastasis.
Definition
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Primary malignant epithelial tumor of the small intestine
Incidence and location
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Most common malignancy of the small intestine (30% to 50% of small bowel malignancies)
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Overall rare lesions, 2% of GI tumors, and 1% of GI cancer deaths
Gender, race, and age distribution
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Presents in older adults (median 67 years)
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Male predominance
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More common in African-Americans than whites
Clinical features
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Vast majority of cases are sporadic
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Similar to colorectal adenocarcinomas in risk factors and development from sporadic adenomatous polyps
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Minority arise in the background of predisposing condition: most commonly FAP, GSE, and Crohn’s disease
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Common symptoms: abdominal pain, obstruction, occult GI bleeding
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Combination of obstructive jaundice with occult GI bleeding characteristic of ampullary tumors
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Most patients present with advanced disease (stage III or IV)
Prognosis and therapy
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Poor outcome in all locations
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5-year disease-free survival rate approximately 30%
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Most deeply invasive and metastatic at time of diagnosis
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Proximal lesions: pancreaticoduodenectomy or endoscopic polypectomy or mucosectomy (polypoid or superficial tumors)
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Distal lesions: segmental resection with accompanying mesentery
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Chemotherapy and radiation appear to have little proven role
Pathologic features
Gross findings
The macroscopic appearance depends largely on the site of the adenocarcinoma. The majority of the duodenal and ampullary tumors are small exophytic masses at the time of presentation. Distal tumors tend to be large, annular, constricting (“apple core”) lesions with circumferential involvement of the bowel wall. Rarely, tumors can have a linitis plastica-like appearance. Macroscopic evaluation and tissue sampling should capture the data necessary for TNM staging ( Table 6-1 ). As in the colon, depth of invasion and serosal involvement must be documented. Duodenal adenocarcinomas requires additional sampling to evaluate the depth of retroperitoneal extension and involvement of the pancreas.
| T—Primary Tumor | N—Regional Lymph Nodes | M—Distant Metastasis | Stage Grouping | |||
|---|---|---|---|---|---|---|
| TX—Primary tumor cannot be assessed | NX—Regional lymph nodes cannot be assessed | M0—No distant metastasis | Stage 0 | Tis | N0 | M0 |
| T0—No evidence of primary tumor | N0—No regional lymph node metastasis | M1—Distant metastasis | Stage I | T1, T2 | N0 | M0 |
| Tis—Carcinoma in situ | N1—Metastasis in 1 to 3 regional lymph nodes | Stage IIA | T3 | N0 | M0 | |
| T1—Tumor invades lamina propria, muscularis mucosa or submucosa | N2—Metastasis in 4 or more regional lymph nodes | Stage IIB | T4 | N0 | M0 | |
| T1a—Tumor invades lamina propria or muscularis mucosa | Stage IIIA | Any T | N1 | M0 | ||
| T1b—Tumor invades submucosa | Stage IIIB | Any T | N2 | M0 | ||
| T2—Tumor invades muscularis propria | Stage IV | Any T | Any N | M1 | ||
| T3—Tumor invades subserosa or nonperitonealized perimuscular tissue (mesentery or retroperitoneum * ) with extension 2 cm or less | ||||||
| T4—Tumor perforates visceral peritoneum or directly invades other organs or structures (includes other loops of small intestine, mesentery, or retroperitoneum more than 2 cm and abdominal wall by way of serosa; for duodenum only, invasion of pancreas) | ||||||
* The nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, part of the retroperitoneum.
Microscopic findings
Small bowel adenocarcinomas are histologically similar to colorectal adenocarcinomas (see Figs. 6-2 and 6-3 ). They are characterized by cellular pleomorphism, complex glandular architecture, luminal necrosis (so-called dirty necrosis), and invasion of the lamina propria and bowel wall. Most adenocarcinomas are moderately differentiated, and one third are poorly differentiated. Histologic grading and classification (e.g., mucinous, adenosquamous) have little bearing on prognosis, though, which is primarily a product of anatomic extent, resectability, and lymph node status. The majority of small bowel adenocarcinomas have invaded through the bowel wall by the time of diagnosis. Notably, intramucosal carcinomas of the small bowel are staged as T1 tumors (rather than Tis). This is caused by the rich mucosal lymphatics that confer metastatic potential to these lesions.
Residual adenomatous epithelium from a preexisting adenoma is present in the majority of proximal tumors but often cannot be demonstrated in large, distal small intestinal adenocarcinomas, presumably resulting from tumor overgrowth. Adenomatous epithelium can be mimicked by tumors metastatic to the gastrointestinal mucosa, and a sharp transition from normal to overtly malignant epithelium is highly suggestive of secondary involvement of the mucosa.
Gross findings
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Duodenum (most in the periampullary region) >> jejunum (first 30 cm) > ileum (Crohn’s disease)
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Duodenal and ampullary lesions: smaller exophytic masses
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Distal tumors: large annular, constricting lesions with circumferential bowel wall involvement
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Rarely tumors can have a linitis plastica appearance
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Gross sampling should include data important for TNM staging (see Table 6-1 )
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Sampling background mucosa and assessing for adenoma are important
Microscopic findings
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Similar histologically to colorectal adenocarcinomas
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Adenocarcinoma is characterized by pleomorphism, complex glandular architecture, luminal necrosis, and invasion into the lamina propria and bowel wall
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Most are moderately differentiated, and one third are poorly differentiated
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Degree of differentiation and special histologic subsets (e.g., mucinous, adenosquamous) have little bearing on prognosis
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Majority of small bowel adenocarcinomas have invaded through the bowel wall
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Preexisting adenoma is present in the majority of proximal tumors but often cannot be demonstrated in large distal small intestinal adenocarcinomas
Immunohistochemistry
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Immunohistochemistry is primarily used to exclude metastatic disease, specifically, metastatic adenocarcinomas (e.g., colon, breast, lung) or other mimickers of poorly differentiated tumor (melanoma and lymphoma)
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Coordinate labeling for CK7/CK20 or CK7+, CK20—might be helpful to rule out metastatic colon adenocarcinomas
Differential diagnosis
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Metastatic adenocarcinomas (e.g., colon, breast, ovary, lung)
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Poorly differentiated malignancies (e.g., lymphoma, melanoma)
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Endometriosis
Differential diagnosis
The main differential diagnostic consideration is metastatic disease, because the small intestine is the most common gastrointestinal site for metastatic disease. Immunohistochemistry is primarily used to exclude metastatic disease, specifically, metastatic adenocarcinomas (e.g., colon, breast, lung) or other mimickers of poorly differentiated carcinoma (e.g., melanoma, lymphoma). Secondary tumors of the small intestine are discussed in more detail later in this chapter.
Prognosis and therapy
Small bowel adenocarcinomas are lethal tumors, with a 5-year survival rate of approximately 30%. Survival is diminished in duodenal tumors and in patients older than 75 years of age. Surgery is the treatment of choice and the only modality with curative potential. Small polypoid or superficial tumors may be amenable to endoscopic polypectomy, mucosectomy, or, in the duodenum, a transduodenal resection. Larger proximal lesions may require pancreaticoduodenectomy, and distal tumors require segmental resection with accompanying mesentery. Chemotherapy and radiation have little role in small bowel adenocarcinomas.
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Adenocarcinomas of the ampulla of vater
The ampulla of Vater is the usual site for convergence of the common bile duct, main pancreatic duct (duct of Wirsung), and duodenum. The ampulla opens through the duodenal papilla and acts as a conduit for bile and pancreatic juices. This unique microenvironment may account for the disproportionate incidence of periampullary adenocarcinomas in the small intestine. Ampullary adenocarcinoma accounts for approximately 7% of carcinomas in the periampullary region and 0.2% to 0.5% of all gastrointestinal malignancies.
Clinical features
Adenocarcinoma of the ampulla of Vater is associated with adenomas in 80% to 90% of cases. The average age of presentation for ampullary adenomas is the middle-50s, whereas adenocarcinoma typicaly presents in the middle-60s. Adenocarcinoma is more common in whites than African-Americans and more common in men than women. Ampullary adenomas and adenocarcinomas are far more likely to become symptomatic at an earlier stage than other small intestinal adenocarcinomas. Obstruction of the ampulla frequently produces jaundice and bile duct dilatation and occasionally results in pancreatitis, cholelithiasis, or choledocholithiasis. Other findings are nonspecific and include weight loss, abdominal pain, and occult bleeding. Typical laboratory abnormalities include increased bilirubin, ALT, AST, and alkaline phosphatase. Ampullary adenomas and adenocarcinomas are visualized endoscopically or, if large enough, by CT. Endoscopic ultrasound (EUS) can also be used to evaluate for invasion.
Definition
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Primary malignant epithelial tumor of the ampulla of Vater
Incidence and location
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7% of all carcinomas in the periampullary region
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Overall rare lesions, 0.2% to 0.5% of GI tumors, and approximately 0.2% of GI cancer deaths
Gender, race, and age distribution
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Presents in older adults (mid-60s)
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Male predominance
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Asian-Pacific Islander > whites > African-Americans
Clinical features
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Vast majority of cases are sporadic
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Minority arise in the background of predisposing condition, most commonly FAP
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Common symptoms: obstructive jaundice, occult GI bleeding, abdominal pain
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Most patients present with regional disease (stage I or II)
Prognosis and therapy
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Pancreaticoduodenectomy
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5-year disease-free survival rate approximately 40%
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Intestinal type has a better prognosis than pancreatobiliary type
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Chemotherapy and radiation appear to have little proven role
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