Residents' Section
Structured Review
Primary Malignant Diseases of the Small Intestine
Audio Available | 
Share
Keywords: adenocarcinoma, carcinoid tumors, neoplasms, oncologic imaging, small intestine
- Key Points
Histologic subtypes of neoplasms of the small intestine (SI) have a predilection for different regions along the SI tract: Adenocarcinoma most commonly involves the duodenum and jejunum while carcinoid tumors are more commonly found in the ileum.
Carcinoid tumors are the most common malignant neoplasms of the SI. The primary lesion may be seen as a relatively small and avidly enhancing nodule, but metastatic spread to the mesentery and resulting desmoplastic response creates more conspicuous imaging changes such as local fat stranding, spiculation, and punctate calcification.
More than half of SI adenocarcinomas occur in the duodenum, most of which are polypoid and arise in the periampullary region. In contrast, adenocarcinomas arising beyond the duodenum are often annular, constricting lesions with shouldered borders.
Imaging appearances of SI lymphoma are protean, ranging from a solitary polypoid mass to pronounced segmental mural thickening accompanied by aneurysmal luminal dilatation.
In day-to-day practice, the radiologist encounters secondary neoplasms more frequently than primary neoplasms of the SI; hematogenous spread of melanoma, lung and breast primaries, and peritoneal dissemination of ovarian, gastric, and colonic neoplasms are commonly recognized.
In this article we outline the important pathophysiologic characteristics of primary neoplasms of the small intestine (SI) including their changing epidemiology, risk factors for development, and relative frequency in each individual SI segment. We discuss lesser-known “hot spots” of SI malignant disease, and for each histologic subtype we describe the key imaging findings and provide examples of these findings on barium, CT, and MRI studies. We should state that primary malignant diseases of the SI are rare and that in day-to-day practice the radiologist may, in fact, be more likely to encounter secondary neoplasms of the SI, which are also briefly discussed in this article.
| Pathophysiology |  |
|---|
The epidemiology of primary SI malignancy is changing. In comparison with the incidence rates of colorectal neoplasms, which have been stable or decreasing over time, the incidence of SI malignancies in developed countries has increased significantly over the past 30 years. This change is primarily driven by the rising incidence of SI carcinoid tumors [1, 2].
In 1987, the most common histologic types of primary SI malignancies in the United States were adenocarcinoma (45%), carcinoid tumor (29%), lymphoma (16%), and sarcoma (10%) [3]. By the year 2000, the incidence of carcinoid tumor exceeded that of adenocarcinoma, rising to represent 44% of all SI neoplasms in 2005. This change reflects a fourfold increase in the incidence of SI carcinoid tumors over a 30-year period [1]. It should be noted however similar changes in incidence in Sweden and the United Kingdom have been ascribed to changes in disease classification and to improvements in endos-copy and imaging techniques [2, 4].
Primary neoplasms of the SI have a slight male predominance, and the incidence rates of SI carcinomas and carcinoid tumors are higher in black patients compared with white patients in the United States [5]. In contrast, white men are found to have the highest rates of lymphomas and sarcomas [5]. Despite many improvements in medical and surgical treatments over the past 20 years, the 5-year survival for malignant neoplasms of the SI, in general, remains unaltered for all histologic subtypes [1]. Primary SI neoplasms often present at an advanced stage which can be explained, at least partially, by the nonspecific nature of the clinical manifestations of these tumors [6]. When patients present with these nonspecific symptoms at an early stage of disease suboptimal imaging techniques have been shown to contribute significantly to delays in patient diagnosis and subsequent management [7].
Careful fluoroscopy with palpation and rotation tailored to the individual patient is known to result in improved detection of small SI lesions and advanced cross-sectional imaging techniques offer great promise although diagnostic pathways still vary according to local availability and expertise [8]. Sustained knowledge of the pathophysiologic characteristics of SI neoplasms and of the technical challenges in imaging SI neoplasms is therefore vital to making the correct diagnosis of this rare disease.
It has long been recognized that subtypes of SI neoplasms have a predilection for specific regions along the SI tract [3]. Adeno-carcinoma is the malignancy most commonly affecting the duodenum and jejunum, representing approximately two thirds of duodenal neoplasms [9] and approximately half of all jejunal neoplasms. The incidence of adenocarcinoma decreases progressively along the remainder of the SI [1]. Midgut carcinoid tumors are seen most commonly in the ileum, representing approximately two thirds of ileal neoplasms. SI lymphoma is more homogeneously distributed along the SI tract according to the pathologic data from the U.S. National Cancer Data Base (1985–2005) [1, 10], but other studies involving smaller numbers of patients show an increased predilection for the distal ileum [11, 12]. The percentages of SI neoplasms by histologic subtype encountered in each individual segment are presented in Table 1.
Although malignancy is reported to account for only 0.5–3.2% of all complications of Meckel diverticulum (MD), this region has been designated a “hot spot” for SI neoplasia because of the high incidence of malignancy per unit length when compared with the remainder of the SI [13]. In one recent study, investigators examining 163 cases of MD cancer and 6214 cases of non-MD ileal cancer between 1973 and 2006 from the Surveillance, Epidemiology, and End Results (SEER) database found the risk of MD cancer to be 70 times higher per unit length of bowel than non-MD ileal cancer [10]. In that study, 77% of MD neoplasms were carcinoid tumors and 11% were adenocarcinomas. Sarcomas constituted 10% and lymphomas, 1%.
Data from the largest and most recent epidemiologic series to date show that SI neoplasm size at presentation varies by histo-logic subtype; sarcomas were, on average, larger than adenocarcinomas, which in turn were typically larger than carcinoid tumors [1]. The mean tumor size for sarcomas was 7.5 cm; adenocarcinomas, 4.0 cm; and carcinoid tumors, 1.6 cm. Distal metastases were seen more frequently in cases of adenocarcinoma than carcinoid tumor (24% vs 15%, respectively) [1]. Nodal involvement was observed more frequently with carcinoid tumors than with adenocarcinomas or stromal tumors (40.7% vs 31.4% and 5.7%, respectively) [1]. Lymphadenopathy is typically bulky in cases of SI lymphoma; this finding has been described in the literature as a useful distinguishing sign [14].
In day-to-day practice, the radiologist will encounter secondary SI neoplasms more frequently than primary SI neoplasms; transcoelomic spread may be related to ovarian, gastric, or colonic primaries [15]. Hematogenous spread is recognized from primary lesions such as melanoma; lung, breast, and cervix tumors; and squamous carcinomas of the head and neck [16].
| Imaging Technique |  |
|---|
Because of the nonspecific and in some cases delayed clinical manifestations, malignant SI neoplasms commonly present with advanced-stage disease; CT abnormalities are readily detectable in up to 90% of cases [17]. Identification of late-stage disease presents little challenge to the radiologist; however, in the case of early-stage tumors presenting with findings such as occult gastrointestinal bleeding, the choice of the appropriate imaging technique may significantly increase diagnostic sensitivity [18]. Capsule endoscopy has been shown, in most comparative studies, to be superior to conventional abdominopelvic CT in the diagnosis of occult gastrointestinal bleeding [18, 19], but the use of neutral or negative contrast agents that distend the small-bowel lumen in addition to multi-phasic contrast-enhanced protocols results in greatly improved lesion visualization [14, 20] (Fig. 1). We believe that CT enterography and enteroclysis should be performed in patients with clinically suspected SI neoplasia who have normal findings on conventional abdominopelvic CT.
 View larger version (340K) | Fig. 1A. —58-year-old man with multiple endocrine neoplasia type 1 who presented with multiple pancreatic and extrapancreatic gastrinomas. A and B, Selected axial contrast-enhanced CT images show multiple small mucosal arterially enhancing nodules (arrow) in second and third portions of duodenum. This case highlights importance of good distention and neutral oral contrast material in detection of small, avidly enhancing neuroendocrine lesions. |
 View larger version (392K) | Fig. 1B. —58-year-old man with multiple endocrine neoplasia type 1 who presented with multiple pancreatic and extrapancreatic gastrinomas. A and B, Selected axial contrast-enhanced CT images show multiple small mucosal arterially enhancing nodules (arrow) in second and third portions of duodenum. This case highlights importance of good distention and neutral oral contrast material in detection of small, avidly enhancing neuroendocrine lesions. |
 View larger version (368K) | Fig. 1C —58-year-old man with multiple endocrine neoplasia type 1 who presented with multiple pancreatic and extrapancreatic gastrinomas. C, Axial contrast-enhanced CT image shows larger arterially enhancing lesion (arrowhead) in head of pancreas. |
MR enterography and enteroclysis are now widely used to assess the extent of inflammatory activity in patients with small-bowel Crohn disease and appear effective in the detection of luminal complications such as secondary neoplasia in this cohort [21] with the major benefit of avoidance of exposure to ionizing radiation. However, the sensitivity of MR enterography appears to be reduced for the detection of polyps smaller than 10 mm [22]. Further improvements in endoscopic technology such as double- or single-balloon enteroscopy are likely to contribute significantly to the diagnosis of SI neoplasms in the future.
| Carcinoid Tumors | |
|---|
Carcinoid tumors are well-differentiated endocrine neoplasms. Their pathogenesis remains almost entirely unknown apart from an association with multiple endocrine neoplasia type 1 [23]. Carcinoid tumors commonly arise in the ileum, with most occurring within 60 cm of the ileocecal valve; however, an increasing proportion of carcinoid tumors are also detected in the duodenum. Often measuring less than 2 cm, carcinoid tumors are the smallest malignant neoplasms of the SI.
Cross-sectional imaging may reveal an endoenteric nodule, which typically enhances avidly on arterial phase CT or MR images (Fig. 2). Carcinoid tumors, because of their production of serotonin and other vasoactive substances such as histamine, dopamine, and kallikrein, result in characteristic changes in the mesentery and induction of a strong desmo-plastic reaction with local fat stranding and spiculated or stellate soft-tissue thickening. Calcification may be present in 70% of cases [24]. There may be kinking of the adjacent bowel loops, sometimes resulting in intestinal obstruction, or there may be vascular encasement resulting in segmental bowel wall and fold thickening secondary to ischemia (Fig. 3).
 View larger version (370K) | Fig. 2A. —77-year-old woman with 8-mm primary carcinoid tumor in ileum. A and B, Axial contrast-enhanced CT images show intestinal obstruction, mesenteric vascular congestion, and submucosal edema of number of ileal loops distal to 2.2-cm mass in mesentery (arrow, B). |
 View larger version (352K) | Fig. 2B. —77-year-old woman with 8-mm primary carcinoid tumor in ileum. A and B, Axial contrast-enhanced CT images show intestinal obstruction, mesenteric vascular congestion, and submucosal edema of number of ileal loops distal to 2.2-cm mass in mesentery (arrow, B). |
 View larger version (336K) | Fig. 2C —77-year-old woman with 8-mm primary carcinoid tumor in ileum. C, Axial contrast-enhanced CT image shows small, avidly enhancing intramural nodule within distal ileum (arrow); this finding is consistent with primary carcinoid tumor. |
 View larger version (472K) | Fig. 3A. —73-year-old man with carcinoid tumor. A, Coronal CT image shows poorly circumscribed, spiculated, and partially calcifi ed mesenteric soft-tissue mass (arrow) that is causing distal vascular insuffi ciency. |
 View larger version (376K) | Fig. 3B. —73-year-old man with carcinoid tumor. B, Axial CT image shows segmental fold thickening and submucosal edema of distal jejunum consistent with ischemia. |
On barium examinations, mural thickening and thickening of the valvulae conniventes are seen in the earlier stages of disease. As submucosal carcinoid tumors grow, they may ulcerate, producing a target or bull's-eye appearance that can also be seen with metastatic melanoma or breast cancer, lymphoma, and Kaposi sarcoma [25]. Metastatic spread to the mesentery may result in a desmoplastic reaction, which can be manifested as crowding of the folds at the edge of the tumor progressing to angulation and kinking of the adjacent small-bowel loops [24]. Hepatic metastases are seen slightly more frequently with carcinoid tumors than with other primary SI neoplasms [1] and may result in carcinoid syndrome; carcinoid syndrome is characterized by flushing, diarrhea, palpitations, and wheezing. Two thirds of patients with carcinoid syndrome may have carcinoid heart disease [26], which results in tricuspid insufficiency; signs on MDCT include a dilated right atrium and thickening of the right ventricular trabeculae and chordae tendineae [27].
| Adenocarcinoma | |
|---|
Primary adenocarcinoma of the SI is a chemoresistant tumor with an aggressive clinical nature [28]. Poor prognostic indicators include T3 disease (TNM staging: tumor has penetrated through the mucosa, submucosa, and muscularis propria and into the subserosa but not through the serosa) and T4 disease (tumor has penetrated through the serosa and may have invaded nearby tissues or organs), N1 and N2 lymph node metastasis, and distal location along the SI [29]. More than half of SI adenocarcinomas occur in the duodenum, and most arise in the periampullary region [30]. Early SI adenocarcinomas may be endoenteric; have a polypoid morphology [24]; and may be associated with an intussusception. More advanced lesions become annular and constricting with shouldered borders [24]. Ileal adenocarcinomas are relatively rare apart from a notably increased incidence in patients with Crohn disease [31]. An increased risk of SI adenocarcinomas is also seen in celiac disease and in a number of familial cancer syndromes including Peutz-Jeghers syndrome, familial adenomatous polyposis, and hereditary nonpolyposis colon cancer, which is thought to be responsible for 5–10% of all SI adenocarcinomas [32].
Unlike carcinoid tumors of the SI, adenocarcinomas enhance mildly after administration of IV contrast material on cross-sectional imaging. They are classically short and signs of partial or complete small-bowel obstruction may be evident at presentation because of their predominantly radial growth pattern (Fig. 4). Early adenocarcinomas may be identified on cross-sectional imaging as a focal region of wall thickening (< 1.5 cm thick and 2–4 cm long) without aneurysmal dilatation, a focal mass, a small ulcerating lesion, or an intussusception.
 View larger version (334K) | Fig. 4A. —48-year-old man with adenocarcinoma of jejunum on background of refractory celiac disease. A and B, Axial CT images show high-grade obstruction of stomach and proximal duodenum (arrow, A) immediately proximal to irregularly enhancing, annular, constricting mass lesion (arrow, B) in proximal jejunum. |
 View larger version (355K) | Fig. 4B. —48-year-old man with adenocarcinoma of jejunum on background of refractory celiac disease. A and B, Axial CT images show high-grade obstruction of stomach and proximal duodenum (arrow, A) immediately proximal to irregularly enhancing, annular, constricting mass lesion (arrow, B) in proximal jejunum. |
On barium studies, late-stage SI adenocarcinomas appear as apple-core lesions similar to those found in large-bowel barium examinations. Advanced SI adenocarcinomas are typically rigid, with a fixed appearance during compression, and magnified views may show mucosal ulceration and overhanging borders [24].
| Lymphoma | |
|---|
Lymphoma of the SI may be primary or may relate to secondary involvement from systemic disease. The diagnosis of primary lymphoma of the SI requires that there is no peripheral or mediastinal lymphadenopathy, no evidence of hepatic or splenic involvement, a normal WBC differential, and that tumor involvement is predominantly in the gastrointestinal tract [33]. Secondary gastrointestinal involvement is comparatively frequent, occurring in approximately 10% of patients with limited-stage non-Hodgkin lymphoma at the time of diagnosis and in up to 60% of those dying of advanced non-Hodgkin lymphoma [34]. Primary lymphoma of the SI represents a heterogeneous group of disorders with variable clinical and pathologic features and a recognized east-west contrast in disease distribution [35]: Approximately 10% of primary gastrointestinal lymphomas arise in the SI in westernized countries, whereas 75% of gastrointestinal lymphomas arise in the SI and are typically associated with immunoproliferative small intestinal disease in the Middle East [36]. Gastric lymphoma constitutes the majority of cases (75%) of gastrointestinal lymphoma in western countries [37], but SI lymphomas outnumber gastric lymphomas in the Middle and Far East [38]. Colonic involvement is seen in 7% of primary gastrointestinal lymphomas in westernized countries but is predominantly due to disease spanning the ileocecal region [37]. Conditions predisposing to SI lymphoma in the United States include autoimmune syndromes such as celiac disease, chronic immunosuppression secondary to AIDS or long-standing immunosuppressive therapy, Crohn disease, radiation therapy, and nodular lymphoid hyperplasia [39].
Cross-sectional imaging findings are protean, representing the broad morphology and stage of presentation of the disease. Imaging appearances range from a solitary, endoenteric polypoid mass to multiple nodules to the more infiltrating form, which is associated with mural thickening and with destruction of the muscle wall and myenteric plexus, resulting in luminal dilatation. Obstruction is a less prominent feature of primary lymphoma of the SI and, when present, is usually related to hypomotility of the involved segment [40] in contradistinction to the occlusive intestinal obstruction typical of SI adenocarcinoma. SI lymphomas may also display exophytic, exoenteric growth characteristics with necrosis; cavitation; and, rarely, fistula formation [24]. SI lymphomas usually have a more homogeneous attenuation on CT and typically show less contrast enhancement than other neoplasms of the SI [41] (Fig. 5). As we stated previously, regional lymphadenopathy is typically bulky and this finding may be useful in differentiating lymphoma of the SI from other primary lesions [14].
 View larger version (367K) | Fig. 5A. —65-year-old man with primary non-Hodgkin lymphoma of jejunum. A and B, Axial (A) and coronal (B) reformatted CT images show marked wall thickening with aneurysmal dilatation (arrow) of involved segment and relatively homogeneous wall enhancement. |
 View larger version (366K) | Fig. 5B. —65-year-old man with primary non-Hodgkin lymphoma of jejunum. A and B, Axial (A) and coronal (B) reformatted CT images show marked wall thickening with aneurysmal dilatation (arrow) of involved segment and relatively homogeneous wall enhancement. |
| Gastrointestinal Stromal Tumors | |
|---|
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that arise from the interstitial cells of Cajal in the subepithelial bowel wall. GISTs represent less than 10% of all primary SI neoplasms [42] and may arise in any segment of the alimentary tract. They also may occasionally arise from peritoneal structures such as the omentum or small intestinal mesentery. GISTs are often exoenteric but can result in mucosal ulceration; less commonly, GISTs may grow in an endophytic intraluminal direction (Fig. 6). Exoenteric GISTs are typically larger than other SI neoplasms at the time of diagnosis, sometimes growing to more than 30 cm [1].
 View larger version (389K) | Fig. 6A. —69-year-old woman with gastrointestinal stromal tumor of duodenum. A and B, Selected axial CT images show focal submucosal mass (arrow) arising within second portion of duodenum is causing marked luminal stenosis (arrowheads). |
 View larger version (401K) | Fig. 6B. —69-year-old woman with gastrointestinal stromal tumor of duodenum. A and B, Selected axial CT images show focal submucosal mass (arrow) arising within second portion of duodenum is causing marked luminal stenosis (arrowheads). |
GISTs display highly variable clinical behavior. Their classic smooth, lobulated contour on cross-sectional imaging does not exclude malignancy. GISTs that are large may display central necrosis, dystrophic calcification, and occasionally evidence of hemorrhage. Large GISTs that display signs of direct extension into adjacent organs and vessels are more likely to metastasize [43]. Submucosal GISTs are evident as smooth filling defects with or without mucosal ulceration on barium examinations. Exophytic GISTs may be identified on imaging only by the displacement of adjacent bowel loops [24].
| Conclusion | |
|---|
The epidemiology of primary neoplasms of the SI is rapidly changing primarily because of the rising incidence of carcinoid tumors. The location, size, and morphologic characteristics of a mass visualized on imaging provide the radiologist with a basis for a rational differential diagnosis. Radiologists should be aware of the many risk factors for primary neoplasms of the SI and of the emerging role of cross-sectional enterography and enteroclysis in identifying early-stage disease, thereby increasing the chances of complete surgical resection and improved survival.
WEB
This is a web exclusive article.
| References | |
|---|
