Epidemiology, clinical features, and types of small bowel neoplasms

Authors
James C Cusack, Jr, MD
Michael J Overman, MD
Robert A Wolff, MD Section Editor
Kenneth K Tanabe, MD Deputy Editor
Diane MF Savarese, MD

Last literature review version 17.1: January 2009 | This topic last updated: January 18,
2009 (More)

INTRODUCTION The diagnosis of small bowel tumors is often difficult due to the rarity
of these lesions, and the nonspecific and variable nature of the presenting signs and
symptoms. Thus, delay in diagnosis is common, which may result in the discovery of
disease at a late stage and a poor treatment outcome.
Several tumors can arise within the small bowel, both malignant (adenocarcinoma,
carcinoid, lymphoma, and sarcomas) and benign (adenoma, leiomyoma, lipoma).
Epidemiology, clinical manifestations, and specific tumor types will be reviewed here.
Diagnosis, staging, and management of small bowel tumors are discussed separately. (See
"Diagnosis and staging of small bowel neoplasms" and see "Treatment of small bowel
neoplasms").

TYPES OF TUMORS A variety of tumors, both malignant and benign, may arise within
the small intestine.

Malignant tumors The distribution of histologic types of small bowel malignant tumors
is changing, largely because of the increasing incidence of carcinoids. In 1987, the most
common histologic types of malignant tumors of the small intestine in population-based
registry data from the Surveillance, Epidemiology and End Results (SEER) program of the
National Cancer Institute were adenocarcinoma, 45 percent; carcinoid, 29 percent;
lymphoma, 16 percent; and sarcoma,10 percent [1]
In the year 2000, carcinoid tumors surpassed adenocarcinomas as the most common small
bowel tumor reported to the National Cancer Data Base (NCDB) [2] . Between 1985 and
2005, the proportion of patients with carcinoids increased from 28 to 44 percent, while the
proportion of adenocarcinoma decreased from 42 to 33 percent. The proportion of patients
with stromal tumors and lymphoma remained essentially stable (17 and 8 percent,
respectively).

Although these malignancies may be found throughout the different regions of the intestine,
certain subtypes have a predilection for specific regions (show table 1) [1] .
Adenocarcinoma is the most common malignancy affecting the duodenum, carcinoid is the
most common tumor in the ileum, while sarcomas and lymphomas can develop throughout
the entire small bowel [2,3] . In a registry-based series of 67,843 cases of small bowel
malignancy reported to the NCDB between 1985 and 2005, the distribution of tumor type
according to small bowel location was [2] : Duodenum - adenocarcinoma 64 percent,
carcinoid 21 percent, lymphoma 10 percent, sarcoma 4 percent Jejunum - adenocarcinoma
46 percent, lymphoma 21 percent, sarcoma 17 percent, and carcinoid 17 percent Ileum carcinoid 63 percent, adenocarcinoma 19 percent, lymphoma 14 percent, and sarcoma 5
percent
Largely as a result of these differences in distribution, the reported relative incidence of
each histology varies considerably with the patient population under study [4-6] .

Benign lesions Benign lesions that may arise in the small bowel include adenomas,
leiomyomas, fibromas, and lipomas.

EPIDEMIOLOGY The following sections will discuss general aspects of the

epidemiology of small bowel tumors. Specific epidemiologic aspects of the individual tumor
types are discussed below.
Malignancies involving the small intestine are rare. There are approximately 6110 new
cases and 1110 patient deaths annually in the United States [7] . Although the small
intestine represents approximately 75 percent of the length and over 90 percent of the
surface area of the alimentary tract, small bowel malignancies account for only 2 percent of
all gastrointestinal (GI) neoplasms and less than 0.4 percent of all cancers in the United
States [7,8] .
By contrast, approximately 148,810 new cases of large bowel cancer are diagnosed each
year in the United States. Several theories, based upon the unique microenvironment of the
small intestine, have been proposed to explain the low rate of small bowel neoplasms
relative to large bowel cancer [1,9] : The more dilute and liquid contents of the small bowel
may cause less mucosal irritation than the more solid contents of the colon. The relatively
rapid transit of intestinal contents through the small bowel may provide for a shorter
exposure to carcinogens. The much lower bacterial load (particularly anaerobic bacteria) in
the small bowel may result in less conversion of bile acids into potential carcinogens by
anaerobic organisms. Benzpyrene, a known carcinogen present in food, is converted to
less toxic metabolites by benzpyrene hydroxylase, which is present in higher
concentrations in the small intestine compared to the stomach and colon. The increased
lymphoid tissue and secretory IgA, found in large quantities in the small bowel, may be
protective.
While rates of large bowel cancer have been stable or decreasing over time, the incidence
of small bowel cancer appears to be increasing, at least in the United States [2,5,10-13] . In
older studies, reported age-adjusted incidence rates of small bowel cancer ranged from 1
to 3 per 100,000 population [4,11,14] . However, in a study analyzing the Connecticut
Tumor Registry, a marked rise in the incidence of small bowel tumors over time was noted

with incidence in the most recent time interval (1994 to 2000) of 14.8 cases per 100,000
population [5]
The degree to which the increased incidence is related to advances in diagnostic imaging is
not known. However, much of the increase appears to be driven by a rising incidence of
small bowel carcinoid tumors [2] . (See "Types of tumors" above).
The mean age at diagnosis
lymphoma presenting at a
carcinoid (67 to 68) [5,15] .
1.5:1 [11] ), and a number
[1,11] .

of a small bowel neoplasm is 65 years old, with sarcoma and

slightly younger age (60 to 62) than adenocarcinoma and
There is a slight male predominance (male to female ratio of
of studies report a higher incidence in blacks than in whites

As a general rule, patients with small bowel adenocarcinoma have a higher incidence of
secondary malignancies involving the colon, rectum, ampulla of Vater, endometrium, and
ovary [16,17] . Conversely, patients with colon adenocarcinoma have an increased risk of
small bowel adenocarcinoma [18] . These findings suggest that similar underlying genetic
or environmental factors are involved in the carcinogenesis of adenocarcinomas arising in
both the small and large intestine. A number of known heritable cancer syndromes are
associated with adenocarcinoma of both the large and small bowel, including hereditary
non-polyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and
Peutz-Jeghers syndrome. (See "Pathogenesis, risk factors, and predisposing conditions"
below).

PATHOGENESIS, RISK FACTORS, AND PREDISPOSING CONDITIONS The etiology

of most small bowel cancers is unknown, although a number of risk factors and
predisposing conditions have been described.
Most small bowel adenocarcinomas arise from adenomas, and the available data suggest
an adenoma-carcinoma sequence driven by a multistep process of specific genetic
changes similar to that described for colorectal cancers, but less well documented or
understood [19] . Single, specific germline mutations underlie some common inherited
syndromes (eg, FAP, HNPCC), while sporadic cancers result from the stepwise
accumulation of multiple somatic mutations, possibly acquired as a result of exposure to
carcinogens within the intestinal lumen. (See "Molecular genetics of colorectal cancer").
As is seen in colon cancer, increasing size of adenomas and the presence of villous
features are both risk factors for the development of invasive carcinoma within an adenoma
[20] (See "Approach to the patient with colonic polyps").
Hereditary cancer syndromes and adenocarcinoma An increased risk of
adenocarcinoma is seen in a number of familial cancer syndromes, many of which are
linked to specific inherited genetic abnormalities: HNPCC is an inherited condition
characterized by loss of DNA mismatch repair, which is caused by a germline mutation in
one allele of a mismatch repair (MMR) gene and inactivation of the second allele by
mutation, loss of heterozygosity, or epigenetic silencing by promoter hypermethylation.
Affected individuals are at risk for colorectal cancer and for several extracolonic cancers,
including adenocarcinomas of the small bowel and endometrium. As with colorectal cancer,
HNPCC is thought to be responsible for approximately 5 to 10 percent of small bowel
adenocarcinomas [21,22] . (See "Clinical features and diagnosis of Lynch syndrome

(hereditary nonpolyposis colorectal cancer)"). The Peutz-Jeghers syndrome is an

autosomal dominant polyposis disorder characterized by multiple hamartomatous polyps
throughout the intestinal tract and a marked increase risk for adenocarcinoma of both the
large and small bowel [23] . (See "Peutz-Jeghers syndrome"). FAP is associated with a
germline mutation in the adenomatosis polyposis coli (APC) gene that promotes tumor
formation in primarily the large intestine but also the duodenum. These patients have
multiple duodenal polyps (with a predilection for the ampullary region) which can undergo
malignant transformation into an adenocarcinoma. In addition, patients with FAP are
predisposed to the development of desmoid tumors, which develop within the small bowel
or its mesentery and are often multiple in number (show radiograph 1) [24,25] . (See
"Desmoid tumors" and see "Clinical features and diagnosis of familial adenomatous
polyposis" and see "Clinical manifestations and diagnosis of ampullary adenomas").

Chronic inflammation A role for chronic inflammation in the etiology of both

adenocarcinoma and lymphoma is suggested by the fact that small bowel disorders
characterized by chronic mucosal inflammation predispose to malignancy. Inflammatory
bowel disease, in particular Crohn's disease, predisposes to adenocarcinoma within the
involved area of small intestine. The risk increases with both extent and duration of small
bowel involvement [26-28] . (See "Clinical manifestations, diagnosis and natural history of
Crohn's disease in adults").
An increased risk of small bowel lymphoma is seen in patients with chronic
immunodeficiency states and autoimmune disorders, including celiac disease [29,30] . (See
"Clinical presentation and diagnosis of gastrointestinal lymphomas" and see "Pathogenesis;
epidemiology; and clinical manifestations of celiac disease in adults").

Neuroendocrine tumors The pathogenesis of carcinoids and other neuroendocrine

tumors arising in the small bowel is almost entirely unknown, apart from an association with
multiple endocrine neoplasia type I (MEN-I) in rare cases [31] . (See "Clinical
manifestations and diagnosis of multiple endocrine neoplasia type 1").

Dietary factors, tobacco, and obesity A number of dietary factors have been
associated with an increased risk of a small bowel cancer in case-control studies, including
intake of alcohol, refined sugar, red meat, salt-cured, and smoked foods [9,12,32,33] .
Tobacco use was associated with cancer risk in two studies, while others suggest no
increased risk in smokers [32,34,35] . Studies on the relationship between obesity and
small bowel malignancy are conflicting, with some showing an increased risk in obese
patients [36-38] , some decreased risk [35] , and others no effect [9] .

CLINICAL PRESENTATION The general aspects of the clinical presentation of benign

and malignant small bowel tumors are discussed here. Specific symptoms associated with
individual tumor types are discussed below (see "Types of tumors" below).

The most common presenting symptom of a small bowel tumor is abdominal pain, which is
present in 44 to 90 percent of patients [39-42] . Pain is typically intermittent and crampy in
nature. Weight loss occurs in 24 to 44 percent, nausea and vomiting in 17 to 64 percent,
and gastrointestinal bleeding in 23 to 41 percent. Intestinal obstruction is more common
than perforation, occurring in 22 to 26 percent compared to 6 to 9 percent, respectively [3941]
As compared to benign tumors, patients with malignant small bowel neoplasms are more
often symptomatic, and the majority of symptomatic small bowel tumors are malignant
[39,43] . Furthermore, symptoms at presentation tend to differ between benign and
malignant tumors. As an example, in a report of 49 patients with a small bowel neoplasm
(17 benign and 32 malignant), 47 percent of benign tumors were asymptomatic (versus 6
percent of malignant tumors) and when symptomatic, they more commonly presented with
acute gastrointestinal hemorrhage (29 versus 6 percent of malignant tumors). Malignant
tumors more commonly presented with abdominal pain (63 versus 24 percent) and weight
loss (38 versus 0 percent). Despite these data, clinical presentation alone does not permit
the distinction between a benign versus a malignant lesion.
The often vague and nonspecific nature of the symptoms makes early diagnosis of a
malignant small bowel tumor difficult. There may be a significant delay from onset of
symptoms to diagnosis (in one series, averaging 30 weeks [39] ). As a result, by the time
patient becomes symptomatic, their disease is usually advanced with either involvement of
regional lymph nodes or distant metastatic sites.
The differential diagnosis is broad given the nonspecific symptoms. More common causes
of small bowel stricturing or obstruction include adhesions, hernia entrapment,
inflammatory bowel disease, endometriosis, splenosis, and complications form appendicitis
or diverticulitis.

ADENOCARCINOMA Adenocarcinomas represent from 25 to 40 percent of small bowel

cancers [1,2,4-6,42,44] . They usually present between the ages of 50 to 70, and there is a
slight male predominance. Age of onset tends to be lower in patients with predisposing
conditions such as Crohn's disease [21,23,45,46] .
As noted above, the risk of small bowel adenocarcinoma is higher in patients who have had
colorectal cancer, suggesting a possible common etiology [18] . (See "Epidemiology"
above).
Also as noted above, inherited syndromes, such as hereditary nonpolyposis colorectal
cancer (HNPCC) or familial adenomatous polyposis (FAP), are responsible for fewer than
10 percent of small bowel adenocarcinomas [47,48] . Patients with HNPCC are at
increased risk for adenocarcinoma throughout the small bowel while FAP increases the risk
for both adenomas and adenocarcinomas of the duodenum. (See "Hereditary cancer
syndromes and adenocarcinoma" above).

Location The incidence of adenocarcinoma is highest in the duodenum (show

endoscopy 1) and decreases progressively throughout the rest of the small intestine. In one
series of 217 patients with small bowel adenocarcinoma, 65 percent had duodenal
primaries [49] .

Explanations for the predilection to the initial part of the small bowel include the metabolism
or dilution of ingested carcinogens in transit through the small bowel or interactions of
carcinogens with pancreaticobiliary secretions [50] . The possible etiologic role of
pancreaticobiliary secretions is supported by a study evaluating 213 cases of duodenal
adenocarcinoma identified from the Los Angeles County Tumor Registry in which the exact
subsite within the duodenum was identified. Fifty-seven percent of cases occurred in
second portion of the duodenum, consistent with a primarily periampullary distribution [50] .

Crohn's disease An exception to the predominantly proximal location is in patients with

Crohn's disease. Seventy percent of adenocarcinomas that arise in this setting are in the
ileum, the primary site of the inflammatory process. (See "Colorectal cancer surveillance in
inflammatory bowel disease").
The development of an adenocarcinoma in patients with Crohn's disease should be
suspected in those with longstanding disease who develop a change in their clinical status,
such as an obstruction that fails to resolve with usual medical treatments [51] . The risk for
adenocarcinoma is directly related to both the extent of small bowel involvement and the
duration of Crohn's disease. In one report, the cumulative risk of a small bowel
adenocarcinoma in patients with small bowel Crohn's disease was 0.2 percent at 10 years
and 2.2 percent at 25 years [52] . The diagnosis is rarely made preoperatively since the
symptoms are similar to those of Crohn's disease with an inflammatory or fibrous stricture
[45] . (See "Clinical manifestations, diagnosis and natural history of Crohn's disease in
adults").

Presenting symptoms The clinical presentation of adenocarcinoma of the small bowel

is nonspecific, with the most frequent symptom being abdominal pain. In a series of 217
patients with small bowel adenocarcinoma, 66 presented with abdominal pain, while
obstruction or bleeding was present in 40 and 24 percent, respectively [49] .
Patients with obstructed duodenal adenocarcinomas may present with vomiting from a
gastric outlet obstruction, or in those with more distal lesions, severe cramping abdominal
pain. Intestinal obstruction can be caused by progression of an apple core lesion (show
radiograph 2) or by a large intraluminal polypoid mass.
Ulceration of the small bowel mucosa is common. This may result in occult GI bleeding or a
chronic anemia.
Largely because of the vague nature of symptoms, the majority of patients have advanced
disease (stage III or IV, show table 2) at diagnosis. In a large series of patients with small
bowel adenocarcinoma derived from the National Cancer Data Base, the distribution of
stage at diagnosis was as follows [53] : Stage 0 to 3 percent Stage I to 12 percent Stage II
to 27 percent Stage III to 26 percent Stage IV to 32 percent
The diagnostic and staging evaluation and treatment of small bowel adenocarcinoma is
discussed elsewhere. (See "Diagnosis and staging of small bowel neoplasms").

NEUROENDOCRINE TUMORS Neuroendocrine tumors of the small bowel are in a

class of tumors referred to as gastroenteropancreatic neuroendocrine tumors. These
tumors have a morphologically unique appearance and are characterized by the production
of biologically active amines. Secretion of these products by the tumor cells can result in a
variety of clinical syndromes caused by the secreted product.
The vast majority are well-differentiated neuroendocrine tumors with the histologic
characteristics of a carcinoid tumor. Other neuroendocrine tumors of the small bowel are
rare when compared to carcinoids. The most common is a gastrinoma of the duodenum.
Although the majority of gastrinomas, 85 percent, are localized to the pancreas,
approximately 15 percent will be found in the upper duodenum. (See "Clinical
manifestations and diagnosis of Zollinger-Ellison syndrome (gastrinoma)" and see
"Somatostatinoma").
Other rarely reported tumors are duodenal somatostatinomas, paragangliomas, and highgrade small cell carcinomas [48, 53].

Carcinoid tumors Carcinoid tumors are well-differentiated neuroendocrine tumors that

are characterized by an indolent disease course. Carcinoids represent between 29 and 40
percent of primary small intestinal malignancies [1,2,4-6] . They have been reported in
patients from 20 to 80 years old, with the highest incidence between age 50 and 60.
Grossly, carcinoids appear as firm intramucosal or submucosal nodules, with a yellow cut
surface due to their high lipid content. They tend to infiltrate the bowel wall and may extend
through the serosa, causing shortening and thickening of the mesentery due to an intense
associated desmoplastic reaction (show radiograph 3). Microscopically, solid nests of
uniform small cells with round or oval nuclei are present with a surrounding intense
desmoplastic reaction (show histology 1). These tumors demonstrated little or no cellular
pleomorphism, hyperchromasia, or increased mitotic activity.
Carcinoids are classified according to their embryologic origin into foregut (bronchus,
stomach, duodenum, and pancreas), midgut (jejunum, ileum, and proximal colon), and
hindgut (distal colon, rectum, and genitourinary tract) types. These subdivisions correlate
with their morphologic pattern, staining characteristics, and clinical behavior (show table 3).
(See "Clinical characteristics of primary carcinoid tumors").
Small bowel carcinoids are most commonly found in the ileum, within 60 cm of the ileocecal
valve [54] . The presence of multiple synchronous nodules in 30 percent of patients
mandates careful inspection of the entire small intestine to exclude other sites of disease
[47]
Because of their indolent growth, most small bowel carcinoids are asymptomatic at
presentation and found only incidentally. Symptoms generally relate to mass effects from
the primary or metastatic tumors or from tumor production of bioactive amines (the
carcinoid syndrome). In symptomatic patients, abdominal pain is the most common initial
symptom, occurring in approximately 40 percent [48] . The pain is most often vague and
nonspecific.

Intermittent obstruction occurs in 25 percent of all small intestinal carcinoids [48,55] .

Obstruction may be caused by intraluminal tumor, but often results from mesenteric kinking
and distortion brought on by tumor invasion and a secondary desmoplastic response. The
latter produces a characteristic radiographic abnormality: a combination of abrupt
angulation with a filling defect in the small bowel (show radiograph 4).
Pain may also arise from vascular compromise secondary to large bulky mesenteric nodal
metastasis, mesenteric vascular invasion, and/or microvascular metastasis [55] . Possibly
contributing to the ischemic process is the vasospastic effect of serotonin produced by the
tumor (see below).
Metastatic disease, which is present in 90 percent of symptomatic patients, correlates not
only with the depth of invasion and location, but also the size of the primary lesion. For
carcinoids <1 cm, the risk of metastasis is 2 percent for appendiceal, 15 to 18 percent for
small bowel, and 20 percent for primary rectal lesions. In contrast, once carcinoid tumors
exceed 2 cm, 33 percent of appendiceal, 86 to 95 percent of small bowel, and almost all
rectal primaries will have metastasized to liver or, to a lesser degree, lungs and bone [56] .

Carcinoid syndrome Carcinoid tumors are characterized by their ability to secrete

serotonin and other bioactive products (show table 4); however, the carcinoid syndrome
occurs in only 10 percent of intestinal tumors, usually in an advanced metastatic stage
[54,56] . Symptoms generally occur when the secretory products of these tumors gain
direct access to the systemic circulation, thus avoiding metabolism in the liver. This
scenario occurs in the following situations: Hepatic metastases Extensive retroperitoneal
disease with venous drainage directly into the paravertebral veins An extraintestinal
primary carcinoid tumor (eg, bronchial, ovarian, or testicular)
Ninety percent of cases of carcinoid syndrome occur in patients with midgut tumors. (See
"Clinical characteristics of primary carcinoid tumors").
The symptoms associated with carcinoid syndrome are watery diarrhea, flushing, sweating,
wheezing, dyspnea, abdominal pain, hypotension, and/or right heart failure due to tricuspid
regurgitation or pulmonic stenosis caused by endocardial fibrosis (show table 5). Facial
edema is often present. The flush is often dramatic and manifests as an intense purplish
color on the upper body and arms; it can be precipitated by consuming alcohol, blue
cheese, chocolate, red wine, or with exercise. Repeated attacks can lead to the
development of telangiectasias and permanent skin discoloration. (See "Clinical features of
the carcinoid syndrome").
A life-threatening form of carcinoid syndrome called carcinoid crisis is usually precipitated
by a specific event such as anesthesia, surgery, or chemotherapy. The manifestations
include an intense flush, diarrhea, tachycardia, hypertension or hypotension,
bronchospasm, and alteration of mental status. The symptoms are usually refractory to fluid
resuscitation and administration of vasopressors.

PRIMARY GASTROINTESTINAL TRACT LYMPHOMA Lymphoma may arise as a

primary neoplasm in the intestinal tract or as a component of systemic disease with
gastrointestinal (GI) involvement. The diagnosis of a primary GI lymphoma requires the
following [57] : No peripheral or mediastinal lymphadenopathy A normal white blood cell

count and differential on the peripheral blood smear Tumor involvement must be
predominantly in the GI tract No evidence of liver or spleen involvement [58,59]
Primary GI tract lymphoma is the most common extranodal form of lymphoma; the stomach
and small bowel are the most common sites. As an example, in a study of 371 patients
registered in a German multicenter treatment study for GI lymphomas, the following sites
were involved [60] (see "Clinical presentation and diagnosis of gastrointestinal
lymphomas"): Stomach - 75 percent Small bowel (including duodenum) - 9 percent
Ileocecal region - 7 percent More than one GI site - 6 percent Rectum - 2 percent Diffuse
colonic involvement - 1 percent
In the Middle East, 75 percent of GI lymphomas originate in the small bowel and are
associated with immunoproliferative small intestinal disease (IPSID); synonyms include
Mediterranean lymphoma and alpha heavy chain disease. By contrast, small intestinal
lymphomas are less common in industrialized nations and are not of the IPSID type. (See
"Classification and pathology of gastrointestinal lymphomas").
In the United States, small bowel lymphoma occurs predominantly in adults, peaking in the
seventh decade, and 60 percent of patients are male [61] . Some of the predisposing
conditions include: Autoimmune diseases Immunodeficiency syndromes (eg, AIDS) Longstanding immunosuppressive therapy (eg, posttransplantation) Crohn's disease Radiation
therapy Nodular lymphoid hyperplasia
The incidence of primary intestinal lymphoma in the United States doubled between 1985
and 1990 [62] . Among the factors implicated in this increase are the increasing number of
immunocompromised patients (eg, AIDS, transplantation recipients) and the increasing
immigration from third world countries.
Lymphomas arise from the lymphoid aggregates in the submucosa. The distribution of
lymphoma in the small intestine parallels the distribution of lymphoid follicles, with the
lymphoid-rich ileum representing the most common location. As with sarcoma, lymphomas
are characteristically bulky tumors; approximately 70 percent are larger than 5 cm in
diameter at presentation.
Most patients present with abdominal pain, anorexia, and weight loss (show table 6). Less
commonly, infiltration of the mucosa can result in ulceration and bleeding, and extension to
the serosa and adjacent tissues may result in a large obstructing mass with or without
intussusception and crampy abdominal pain (show radiograph 5). The risk of perforation
depends on the site of GI tract involvement; perforation is seen in 9 percent of small bowel
lymphomas and only 2 percent of gastric lymphomas [60] . (See "Clinical presentation and
diagnosis of gastrointestinal lymphomas").
Histologically, these non-Hodgkin lymphomas may be low or high-grade, and they may be
of B-cell or T-cell origin. The REAL/WHO classification system, as is used for other nonHodgkin lymphomas, is predominantly used for classification [63,64] , although an
alternative classification system for primary GI lymphomas has been proposed [65] . The Bcell lymphomas that most often involve the GI tract consist of the mucosa associated
lymphoid tissue (MALT) type, diffuse large B-cell, mantle cell, and Burkitt and Burkitt-like
variants. MALT type tumors occur most often in the stomach, while mantle cell lymphoma
has a predilection for the colon and small intestine. The less common T-cell lymphomas are
most often jejunal. Primary or secondary involvement of the GI tract by Hodgkin lymphoma
is extremely rare [66] . (See "Classification and pathology of gastrointestinal lymphomas").

Histologic and clinical factors associated with prognosis include histological subtype of nonHodgkin lymphoma, histologic grade of differentiation, stage of disease, and International
Prognostic Index (IPI). (See "Management of gastrointestinal lymphomas").

SARCOMA Malignant mesenchymal tumors (sarcomas) represent approximately 10

percent of small bowel neoplasms [1,5,6,42,53,67] and are most common in the jejunum,
ileum, and in a Meckel's diverticulum [68] . The most common type of intestinal sarcoma is
a gastrointestinal stromal tumor (GIST), accounting for 83 to 86 percent of cases [2,69] .
Prior to the identification of GISTs by their molecular characteristics, leiomyosarcomas
represented the most common small bowel sarcoma. However, the majority of these
previously classified leiomyosarcomas in older studies are actually GIST tumors. In a report
of 1091 tumors originally classified as "smooth muscle tumors of the small intestine", 906
(83 percent) were GISTs [69] . Among the 176 non-GISTs, there were 53 sarcomas (mostly
phenotypically undifferentiated), 32 leiomyosarcomas (3 percent of the total), 13
leiomyomas, 14 sarcomatoid epithelial neoplasms, 13 desmoids, 8 schwannomas, and a
variety of other unusual benign and malignant proliferations. (See "Gastrointestinal stromal
tumors, leiomyomas, and leiomyosarcomas of the gastrointestinal tract").
Histologically, GISTs can have a similar morphologic appearance to leiomyosarcomas
(show histology 2) and thus must be differentiated based upon the expression of c-kit (the
CD117 antigen), which represents a component of the KIT tyrosine kinase receptor.
Activating mutations in the KIT oncogene are seen in over 80 percent of all GISTs. A
subset of GISTs lacking KIT mutations have activating mutations in a related receptor
tyrosine kinase, the platelet derived growth factor receptor alpha (PDGFRA). (See
"Diagnosis and staging of small bowel neoplasms", section on Histology and differential
diagnosis).
Common presenting symptoms of small bowel sarcomas include pain, weight loss,
bleeding, perforation, or a palpable mass [70,71] . Because they tend to enlarge
extraluminally, obstruction is rare and typically a late presenting symptom.
The majority of GISTs (60 to 70 percent) are located in the stomach, but the small intestine
is the second most common site (20 percent). Small bowel GISTs are most commonly
located in the jejunum, followed by the ileum and then duodenum. (See "Gastrointestinal
stromal tumors, leiomyomas, and leiomyosarcomas of the gastrointestinal tract", section on
Small intestine).

METASTATIC LESIONS Extraluminal involvement of the small bowel is common in the

setting of widespread peritoneal carcinomatosis. Erosion through the bowel wall into the
lumen can occur, particularly with tumors that have a predilection to involve the peritoneal
cavity, such as ovarian, colon, and gastric cancer.
Hematogenous spread to the bowel is also possible. In studies in which direct extension
from peritoneal metastases was excluded, the most common tumors to hematogenously
spread to the small bowel were melanoma, lung, breast, cervix, sarcoma, and colon [72-74]
. Small bowel is the most common site of gastrointestinal metastases in patients with
metastatic melanoma (show radiograph 6) [75] . (See "Surgical management of metastatic
melanoma", section on Gastrointestinal tract).

BENIGN TUMORS The frequency of benign tumors of the small bowel increases from
the duodenum to the ileum [76] . Of the various histologic types, adenomas, leiomyomas
and lipomas are the most common.

Adenomas There are three major types of benign small bowel adenomas: simple
villous, tubular, and Brunner's gland adenomas.
Villous adenomas carry a significant potential for malignant transformation. Malignant cells
are found in as many as 42 percent of duodenal villous adenomas [77] , with an adenomacarcinoma sequence comparable to that of colorectal cancer [78] . Familial adenomatous
polyposis (FAP) is a risk factor; 80 percent of affected patients develop duodenal
adenomas, which are often multiple [79] . Adenomas in the duodenum have a predilection
for the papilla (Ampulla of Vater). (See "Clinical manifestations and diagnosis of ampullary
adenomas" and see "Screening and management strategies for patients and families with
familial colon cancer syndromes", section on Surveillance for extracolonic tumors).
Coincident colonic adenomas are common in patients who have villous adenomas of the
papilla or duodenum, suggesting that colonoscopy is an important component of the
diagnostic workup. The usual presentation is with bleeding or obstruction of either the small
bowel or biliary tract. On biopsy, the superficial part of the lesion may appear benign with
areas of adenocarcinoma in the deeper parts [77] .
Tubular adenomas have a lower malignant potential. They are most common in the
duodenum, are usually asymptomatic, but may present with bleeding or obstruction.
A Brunner's gland adenoma is a rare small bowel neoplasm. It is caused by hyperplasia of
the exocrine glands within the proximal duodenal mucosa. (See "Clinical manifestations
and diagnosis of ampullary adenomas").

Leiomyomas Leiomyomas are single, firm, gray or white, well-defined masses that arise
in the submucosal layer of the wall of the small intestine (show radiograph 7).
Microscopically, they consist of well differentiated smooth muscle cells (show histology 3).
These tumors usually enlarge extraluminally and therefore are not detected until they
outgrow their blood supply, causing central necrosis, ulceration, and bleeding into the
bowel lumen.
In cases in which the tumor extends intraluminally, obstruction may be the initial symptom
(show picture 1). (See "Clinical manifestations and diagnosis of small bowel obstruction").
Leiomyomas are rare; in the series described above, they accounted for only 13 of the
1091 tumors originally classified as smooth muscle tumors of the small intestine (about 1
percent) [69] .
Lipomas Lipomas are the second most common benign tumor arising in the small bowel,
and they occur mostly in the ileum and duodenum. They arise from either submucosal
adipose tissue or serosal fat and may present with obstruction, obscure GI tract bleeding,
or as an incidental finding. These are submucosal lesions with homogeneous fatty tissue
on a cut surface. They have a diagnostic low attenuation appearance on CT scan (show
radiograph 8) [80]

Other benign lesions Desmoid tumors, which are commonly seen in patients with FAP,
may grow intraluminally, causing obstruction, or extraluminally, presenting as a palpable
abdominal mass (show radiograph 1). (See "Desmoid tumors").
Hemangiomas are rare lesions that usually present with bleeding. Hamartomas of the small
intestine are seen in patients with the Peutz-Jeghers syndrome. (See "Peutz-Jeghers
syndrome").

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