Gerald Hurowitz, M.D.·Published 20 January 2008·7 min read
Key points
That malignant tumors of the small intestine are quite uncommon is surprising considering the much higher frequency of malignancies originating in the large intestine and stomach.
Several conditions and diseases are associated with an increased incidence of small bowel adenocarcinoma or lymphoma.
Patients with small intestinal tumors may be anemic and have occult blood in their stools.
Any of the small intestinal malignancies may ulcerate and bleed into the bowel lumen.
Relevant Physiology and Pathophysiology
That malignant tumors of the small intestine are quite uncommon is surprising considering the much higher frequency of malignancies originating in the large intestine and stomach. Liquidity of its contents, low bacterial population, rapid transit, rapid cell turnover, local immune responses, and active detoxifying enzyme systems, alone or in combination, have been suggested as contributing to the infrequency of small intestinal malignant tumors.
There are about 2000 new cases of small bowel cancer per year in the United States. The majority are adenocarcinomas. The disease is rare before age 30, when incidence gradually begins to rise steadily, peaking in the sixth decade. There is a slight preponderance of incidence in males, but no marked social differential. The incidence of small bowel cancer in different geographic regions seems to parallel the incidence of colonic carcinoma. In the Middle East the incidence of primary small intestinal lymphoma appears to exceed the incidence of other small intestinal malignancies.
Adenocarcinomas arise from the crypts of the mucosa of the small intestine.
They develop most commonly in the proximal small bowel and least commonly toward the ileum. Clustering of duodenal adenocarcinomas in the periampullary region has implicated bile in the pathophysiology of these neoplasms. Histologically, adenocarcinomas of the small intestine most often resemble colonic rather than gastric adenocarcinomas. Metastases to local lymphatics are common; hematogenous spread and peritoneal seeding also occur.
Lymphomas originate in lymphoid cells within and beneath the mucosa of the small intestine and are more common in the distal small intestine. Hodgkin's disease is the least common primary lymphoid malignancy of the small bowel. Small bowel lymphomas are often multifocal and may infiltrate beneath the mucosa over a wide area.
The "Mediterranean lymphoma" prevalent in the Middle East appears to be a distinctive pathologic entity. The small intestinal lesion is usually diffuse, and the cells that characterize this neoplasm often have features of plasma cells, histiocytes, and atypical lymphocytes. Mediterranean lymphoma (immunoproliferative small intestine disease) affects the duodenum and proximal jejunum more commonly than the ileum. It may be associated with the production of an abnormal circulating immunoglobulin A (IgA) that contains only alpha chains (alpha chain disease), although not all diffuse mucosal lymphomas of the small intestine produce this immunoglobulin.
The smooth muscle layer of the muscularis externa of the small intestine may give rise to leiomyosarcomas. These are slightly more common in the proximal than in the distal small intestine. They metastasize by hematogenous spread to liver and lung and only rarely to regional lymph nodes.
Written and revised by
Gerald Hurowitz, M.D.
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Several conditions and diseases are associated with an increased incidence of small bowel adenocarcinoma or lymphoma.
Regional Enteritis (Crohn's Disease). Adenocarcinoma of the small bowel occurs more often in patients with regional enteritis than in age-matched controls and affects the ileum more often than the proximal bowel. Patients who have had segments of intestine bypassed surgically may be at higher risk.
Inherited Polyposis Syndromes. Several inherited intestinal polyposis syndromes are associated with an increased incidence of small intestinal adenocarcinoma. In familial adenomatous polyposis and Gardner's syndrome, adenomas and adenocarcinomas of the duodenum occur with increased frequency, particularly in the periampullary region. Small intestinal (especially duodenal) adenocarcinoma has been reported in patients with Peutz-Jeghers syndrome, although the incidence is not high.
Celiac Sprue. An increased incidence of malignancy, especially lymphoma of the small intestine, has been reported in patients with celiac sprue. These lymphomas, derived from intestinal T cells, occur most frequently in the proximal small intestine. The association of celiac sprue with lymphoma has been questioned, because a diffuse intestinal lymphoma can also cause malabsorption, but evidence for this association is increasing. One study indicates that strict adherence to a gluten-free diet decreases the incidence of lymphoma.
Immune Deficiency States. An increased incidence of lymphoma of the small intestine has been suggested in hereditary syndromes of decreased humoral or cellular immunity and also in acquired immunodeficiency. The latter group includes patients with acquired immunodeficiency syndrome and those treated with intensive radiation, chemotherapy, and immunosuppressives.
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Laboratory and Other Diagnostic Tests
Patients with small intestinal tumors may be anemic and have occult blood in their stools. They may be hypoalbuminemic as a result of protein loss from the tumor and obstruction of lymphatics, especially patients with lymphomas that may infiltrate the mesentery. Malabsorption may produce excess fat in the stool, abnormal Schilling and D-xylose test results, prolonged prothrombin time, and low serum calcium and magnesium concentrations.
Most malignant tumors of the small intestine can be detected in carefully performed barium contrast studies. A common error in evaluating patients with abdominal symptoms is to perform only a barium enema and upper gastrointestinal series. These examinations usually demonstrate only the most proximal and distal small bowel loops; therefore a small intestinal series should be performed. The detection of small lesions in the small intestine by barium radiographic study requires a skilled, interested, and attentive radiologist. The use of enteroclysis, or small bowel enema, can provide increased accuracy. In this more invasive technique, barium is instilled directly into the intestine by passage of a tube through the nose or mouth.
Duodenal tumors may be detected and biopsy specimens obtained by upper gastrointestinal endoscopy. Modern fiberscopes may reach the third portion of the duodenum, and longer enteroscopes have been developed. Most of the jejenum can be examined with "push"-type enteroscopes that allow biopsy, and even the ileum can be seen using "sonde" enteroscopes, which rely on peristalsis for passage but have no biopsy capability. Tumors of the terminal ileum may be revealed in some patients if the ileocecal valve is passed with a colonoscope. Peroral biopsy via tubes passed under fluoroscopic control may obtain a biopsy specimen of small bowel malignancy, particularly in diffuse or multifocal lymphoma. Frequently the diagnosis of small bowel malignancy is made by the surgeon at the time of laparotomy, by palpation, and by biopsy.
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Differential Diagnosis
Any of the small intestinal malignancies may ulcerate and bleed into the bowel lumen. Blood loss is generally not massive and may be occult. Leiomyosarcomas may be particularly vascular and may be a cause of gross bleeding with melena or grossly bloody stools. Tumors proximal to the ligament of Treitz occasionally cause hematemesis if they bleed rapidly.
Small bowel malignancies may narrow the intestinal lumen, creating partial obstruction that may cause cramping abdominal pain accompanied by loud peristaltic rushes and abdominal distention. Small bowel adenocarcinomas tend to create a ringlike constriction similar to that created by colonic adenocarcinomas. Small bowel tumors may also act as a lead point for an intussusception, producing intermittent obstruction. Higher grades of obstruction cause backing up of bowel contents, with nausea and vomiting; the vomiting may be feculent if the obstruction is in the distal small intestine and associated with stasis.
Weight loss may be a prominent feature of small bowel malignancies. Malignant tumors in the abdomen frequently cause anorexia and decreased caloric intake. Abdominal pain caused by partial bowel obstruction may be exacerbated by food intake, contributing to anorexia. Bacterial overgrowth in the obstructed small intestine may be a cause of malabsorption, producing steatorrhea and weight loss. Malabsorption is common with diffusely infiltrating small intestinal lymphomas.
Small bowel malignancies can, on occasion, cause acute abdominal catastrophes such as perforation, massive hemorrhage, or acute intestinal obstruction.
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Management
Surgery is usually the first-line therapeutic modality for small bowel malignancy. A localized neoplasm is resected widely to ensure that resection margins are free of tumor. In the case of adenocarcinoma, surgery is the only possibility for cure; recurrences are more likely if the cancer has penetrated the serosa and invaded regional lymph nodes. Chemotherapy and radiation therapy can provide temporary palliation in a few patients with unresectable disease.
Radiation therapy and chemotherapy are important modalities for small bowel lymphomas as primary treatment and as adjuvant therapy after surgical resection. Perforation of the gastrointestinal tract caused by rapid lysis of lymphomatous areas has been described after radiation therapy or chemotherapy. Thus surgical resection with curative intent is widely held as preferable. Involvement of local lymph nodes is generally an indication for postoperative irradiation or chemotherapy. In widespread, unresectable disease, chemotherapy is indicated. Leiomyosarcomas are best treated with surgery. They are radioresistant, and chemotherapy has been largely ineffective.
Author: Charles J. Lightdale
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