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.