Primary small intestine neoplasms are relatively rare, representing only 3 % of all gastrointestinal (GI) cancers and 0.5 % of all cancers in the United States [1]. Although there is a small incidence, a variety of histologic types can arise within the small intestine: carcinoid tumors, adenocarcinoma, sarcomas, and lymphomas. Recently, carcinoid tumors surpassed adenocarcinoma as the most frequent histologic type. Data from National Cancer Database between 1985 and 2005 showed that the proportion of carcinoid tumors increased from 28 % to 44 %, while the proportion of adenocarcinoma decreased from 42 % to 33 % [2]. Generally, carcinoid tumors are more frequent in the ileum, while adenocarcinoma affects the duodenum more often. Sarcomas and lymphomas can develop in the entire organ [2].

There are two histologic types of adenocarcinomas that must be differentiated: pancreatobiliary and intestinal. The first seems to have a worse prognosis [3]. Some hypotheses have been proposed to explain the lower incidence of small intestine adenocarcinoma compared to the large intestine [4]: (1) the increased liquid content and the more rapid transit may provide less exposure to carcinogens and less irritation and (2) the higher concentration of benzpyrene hydroxylase and the much lower bacterial load may result in less carcinogen metabolites.

Data from the United States revealed that the incidence of small intestine cancer is rising [5]. This epidemiologic change seems to be caused by an increase of >fourfold of carcinoid tumors [2]. The incidence is slightly higher in men (1.5:1) [6]. The mean age at diagnosis is 60–62 years and 67–68 years for sarcomas and lymphomas and for adenocarcinoma and carcinoid tumors, respectively [5].

As observed in colon cancer, most small intestine adenocarcinomas arise from adenomas; however, unlike the large intestine, there are few data on this issue [7]. Some hereditary cancer syndromes are related to the development of large and small intestine adenocarcinoma: hereditary non-polyposis colorectal cancer [8], familial adenomatous polyposis [9], and Peutz-Jeghers syndrome [10]. Patients with inflammatory bowel disease are at an increased risk for developing adenocarcinoma, according to the extent and duration of small bowel involvement [11]. There is an association between multiple endocrine neoplasia type I with rare cases of carcinoid tumor of the small intestine [12]. Risk factors for other histologic types are not yet completely known.

The main symptoms are abdominal pain, weight loss, nausea, and vomiting, GI bleeding, and intestinal obstruction. In the case of a duodenal primary mass, jaundice is a possible sign of the disease [13]. Since the symptoms are often vague and non-specific, the level of suspicion of small intestine neoplasms are often low, and this can result in the majority of patients being diagnosed with advanced disease (58 %, stage III or IV) [14].

Carcinoid tumors of the small intestine are more frequently well differentiated. This means that these neoplasms usually have a characteristic morphologic aspect, and they can produce biologically active amines. The majority of these tumors are asymptomatic on presentation due to hepatic metabolism of the active amines and its indolent growth. Metastatic disease is present in 90 % of symptomatic patients. The mass effect of the tumor is generally the cause of symptoms such as abdominal pain and obstruction. Carcinoid syndrome occurs when active amines have gained access to the blood circulation, and it is typically in the setting of liver metastasis [15]. Details on this syndrome are discussed in a separate chapter.

Primary GI lymphoma is the most common extranodal form of lymphoma. The stomach and small intestine are the most common sites [16]. More information on this subject can be found in another chapter. Epidemiology and clinical manifestation of GI stromal tumors are also discussed in another chapter.

The vague and non-specific symptoms in combination with the lack of physical findings can delay the diagnosis for up to several months [17]. The stage of diagnosis is a prognostic factor for overall survival. Therefore, a higher suspicion is necessary when evaluating symptomatic patients. There are radiographic and endoscopic tests to help physicians determine the diagnosis and staging of small intestine cancer; however, there is not a consensus on the right sequence of tests.

Upper endoscopy (UE) may provide a direct evaluation of the mucosa, and it can provide a specimen sample and resection of benign lesions [18]. However, only the duodenum can be assessed by UE. Although colonoscopy can also provide a specimen sample and direct evaluation of the mucosa, it can only assess the terminal ileum [19]. Wireless video capsule endoscopy (VCE) is an interesting option for evaluating the entire small intestine. In a meta-analysis of 24 studies, VCE failed to identify tumors in 20 of 106 cancers cases (false negative rate, 19 %) [20]. In a retrospective study at Mount Sinai Medical Center from 2001 to 2003, 562 individuals with non-specific GI symptoms underwent VCE, which detected small intestine tumors in 8.9 % of the patients with only one false-positive result [21]. However, VCE cannot be performed in patients with a high suspicion of GI obstruction, because there is a high risk of capsule retention, which necessitates emergency laparoscopy [22]. In addition, VCE cannot provide a specimen sample, and it is fundamental to determine the diagnosis of small intestine cancer. Alternatively, double balloon enteroscopy is a very good option when available. It can directly evaluate the small intestine and provide tissue sampling. However, it is a difficult technique, and it is not available at the majority of institutions.

CT is very important in staging, especially of adenocarcinomas. It can provide an evaluation of local and distant commitment caused by the disease. CT can detect abnormalities in up to 80 % of patients with small intestine neoplasms [23]. CT enterography is an option when there is suspicion of GI obstruction and enteroscopy cannot be performed. However, similar to VCE, CT enterography cannot provide a specimen sample. In a study on 219 patients with a high index of suspicion and normal endoscopy, CT enterography detected 155 abnormalities with 5 false-positives. Among 164 patients with a normal result, a small bowel tumor was later found in 9 [24]. PET is largely used in cases of lymphomas and stromal tumors; however, PET is not currently indicated for adenocarcinomas. It can be used to evaluate the response to initial treatment (i.e., a decrease in the uptake value) [25]. The Tumor, Node, and Metastasis Staging System of small intestine cancers is presented as follows [26].

The treatment of carcinoid tumors, sarcomas, and lymphomas arising from the small intestine are discussed in separate chapters for each histologic subtype. The treatment of adenocarcinoma is discussed in the following.