Benign Neoplasms of the Small Intestine


Practice Essentials

Benign tumors of the small bowel are rare clinical entities that often remain asymptomatic throughout life. [12345 Despite comprising 75% of the length and 90% of the surface area of the gastrointestinal (GI) tract, the small bowel harbors relatively few primary neoplasms and fewer than 2% of GI malignancies. [6]

Benign small-bowel tumors may develop as a single lesion or as multiple lesions of several subtypes. Subtypes include the following:

  • Hyperplastic polyps
  • Hamartomas
  • Adenomas
  • Gut stromal tumors
  • Lipomas
  • Hemangiomas
  • Those associated with  Peutz-Jeghers syndrome [7]

A multicenter study from Taiwan found hamartomas and adenomas to be the most common benign small-bowel tumors. [8]

Benign small-bowel tumors are generally characterized by slow growth and delayed clinical presentation. They often remain inherently asymptomatic, only to be discovered incidentally at autopsy.

Strict medical management currently has no role in benign small-bowel tumors. Surgical excision remains the recommended therapy for these tumors. (See Treatment.)

Pathophysiology

Benign small-bowel tumors may be found throughout the duodenum, jejunum, and ileum (in order of increasing frequency). Tumors may be single, multiple, or widespread (ie, as part of a polyposis syndrome). The following three growth patterns have been identified:

  • Intraluminal
  • Infiltrative
  • Serosal

Intraluminal lesions are most often associated with the development of secondary bowel obstruction and intussusception, whereas serosal lesions are linked to small-bowel volvulus.

Several factors have been suggested to explain both the scarcity of small-bowel lesions and the infrequency of their malignant transformation, as follows [9:

  • First, rapid intestinal transit through the small bowel limits contact time to the small-bowel mucosa
  • Second, greater fluidity of small-bowel chyme may dilute luminal irritants
  • Third, alkaline pH may play a role, as may the low bacterial colony counts of the small bowel
  • Finally, higher levels of benzyl peroxidase (thought to detoxify potential carcinogens) have been detected in the small bowel

Together, with increased levels of immunoglobulin A and widespread gut lymphoid tissue, these factors may impede the growth and development of tumors and their malignant transformation.

Epidemiology

Benign small-bowel lesions have been documented in persons of all age groups, though the mean age of presentation reportedly is between the fifth and sixth decades of life. Several series have noted a slight predominance in males compared to females. No racial or ethnic predisposition has been discovered.


History

Clinically, benign small-bowel lesions are characterized by a lack of identifying symptoms. A review of published reports reveals that multiple findings can occur sporadically; no hallmark presentation has been described. Possible signs and symptoms are as follows [2345:

  • Abdominal pain - This is generally nonspecific, dull, and epigastric in location; pain is more commonly associated with larger lesions, which may cause symptoms of intermittent bowel obstruction
  • Constipation
  • Melena
  • Perforation
  • Nausea
  • Diarrhea
  • Gastrointestinal (GI) hemorrhage
  • Volvulus
  • Vomiting
  • Palpable mass
  • Obstruction
  • Anorexia
  • Early satiety
  • Anemia
  • Intussusception

The interval from symptom onset to diagnosis reportedly ranges from less than 1 month to more than 1 year, with a mean symptom duration of 6 months. Despite their frequently unobtrusive nature, benign small-bowel tumors may manifest primarily as secondary complications of their growth. The following may be noted:

  • Bowel obstruction - This is associated with as many as 30% of benign small-bowel tumors, and these tumors remain the leading cause of intussusception in adults
  • Volvulus - Volvulus from serosal ependymal lesions has also been reported
  • GI bleeding - This is a more frequent occurrence, occurring in as many as 38% of lesions in one series; blood loss may be occult, detected as only heme-positive stool, or it may be acute and copious, as with larger vascular lesions; such bleeding may ultimately require transfusion, embolization, and/or emergency surgery
  • Perforation - Free perforation of small-bowel tumors into the peritoneal cavity, with resultant development of peritonitis and requirement for emergency laparotomy, has also been documented

Benign small-bowel tumors may develop as a single lesion or as multiple lesions of several subtypes. The types of tumors include the following:

  • Hyperplastic polyps
  • Adenomas
  • Gut stromal tumors
  • Lipomas
  • Hemangiomas
  • Peutz-Jeghers syndrome

Hyperplastic polyps

Hyperplastic polyps are benign mucosal growths frequently observed in the duodenum and proximal ileum. Frequently discovered upon routine upper endoscopy, the polyps may be single or multiple. They are generally asymptomatic with no malignant potential and may be removed endoscopically with biopsy forceps or an Endosnare.

Adenomas

Three types of small-bowel adenomas have been described, as follows:

  • Adenomatous polyps
  • Brunner gland adenomas [10]
  • Villous adenomas

In general, they may develop as single or multiple lesions, both sessile and pedunculated. Histologically, they appear as intraluminal extensions of the mucous membrane and submucosal architecture with multiple acini supported on a central fibrovascular core. Varying degrees of differentiation are encountered across and within tumors. [11]

Complications of continued growth include obstruction, bleeding, intussusception, and, occasionally, malignant degeneration, particularly with larger villous lesions. [12Specifically, Brunner gland adenomas develop most often along the posterior wall of the duodenum at the junction of the first and second portions. Focal, multifocal, or diffuse, they exhibit benign proliferation of the Brunner glands with scattered ductal and stromal elements.

Villous adenomas, though exceedingly rare, have most frequently been described in the duodenum. [13Bleeding and obstruction are their most common complications, though, like their counterparts in the colon and stomach, they may be associated with malignant degeneration. Villous adenomas larger than 4 cm are at particular risk for malignant elements. [13]

Gut stromal tumors

In several reports, gut stromal tumors (formerly known as leiomyomas and leiomyosarcomas) are the most common symptomatic small-bowel lesions. They have been found in all areas of the small bowel, including within the Meckel diverticulum. Featuring nests of spindle-shaped cells located between the muscularis propria and the muscularis mucosa, these intramural lesions may form intraluminal masses, extraluminal masses, or transmural (dumbbell-shaped) lesions. [14]

Histologic features of smooth muscle may or may not be seen with light microscopy; however, this finding has not yet been assigned any prognostic value. [1516Both focal lesions and annular lesions have been described, often with features of surface ulceration or deeper necrosis. Such degeneration may lead to bleeding and marked hemorrhage, which are the most common complications observed with this family of tumors. Minor bleeding from surface erosion may occur because the tumors are continually buffeted and bathed by intestinal contents. Brisk arterial bleeding may result from necrosis involving tumor arterioles occurring deep within the lesion.

Other complications of gut stromal tumors include bowel obstruction, intussusception, tumor perforation, and potential malignant degeneration. In general, size is the defining characteristic for complications from gut stromal tumors. The larger the tumor, the more likely it is to obstruct or twist within the bowel lumen. Similarly, larger tumors are more likely to outgrow their blood supply, necrose, bleed, and degenerate.

Differentiating between benign gut stromal tumors and malignant gut stromal tumors can be difficult. In several published reviews, benign smooth-muscle tumors are generally two to three times more common than the sarcoma variants. Current diagnostic criteria for pathologic examination of malignancy include the following:

  • Tumor cell size
  • Degree of cellular differentiation
  • Number of mitotic figures per high-power field (hpf)

A finding of more than two mitotic figures per 10 hpf is generally considered worrisome for malignancy. [17]

Lipomas

Small-bowel lipomas are benign submucosal tumors of mesenchymal origin. These tumors are often located in the ileum and may frequently develop as pedunculated or submucosal lesions. They may be sessile or ependymal and may grow undetected to a size sufficient to produce symptoms of colicky abdominal pain and intermittent bowel obstruction. [18Intussusception has also been reported.

Histologic features include collections of mature adipose tissue and fibrous tissue strands. Evidence of surface ulceration, central necrosis, and hemorrhage may be present. Collections of adipose tissue may be found near the ileocecal valve. These deposits may clinically mimic other lesions, both radiographically and endoscopically.

Hemangiomas

Hemangiomas of the small bowel are rare vascular tumors of three types, as follows [1920:

  • Capillary
  • Cavernous (the most common type)
  • Mixed

Hemangiomas may be solitary or multiple and may account for up to 10% of small-bowel lesions. [21]

GI bleeding is a frequent complication. The blood loss may be chronic (resulting in longstanding occult anemia) or profound (necessitating massive transfusions, emergency laparotomy, or both for control of acute hemorrhage). [22 Additional uncommon complications include small-bowel obstruction, intussusception, intramural hematoma, and perforation. With light microscopy, hemangiomas appear as blood-filled sinusoidal spaces intermingled with varying amounts of connective tissue. Occasionally, the lesions contain smooth muscle cells.

Diagnosis and localization of symptomatic lesions remain a challenge. Preoperative arteriography or intraoperative maneuvers, such as transillumination of the bowel or intraoperative ultrasonography, may be employed to increase localization success.

Case reports have documented the successful use of capsule endoscopy to aid in the diagnosis of these often difficult-to-detect lesions. [2324]

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is an autosomal dominant disorder featuring mucocutaneous pigmentation (eg, on the face, lips, and buccal mucosa) and benign GI hamartomas. [725 These polyps may be found in the small bowel in up to 90% of affected individuals. The stomach and the colon are frequently involved, and tumors outside the GI tract are also described.

The hereditary defect is associated with mutation on the LKB1 gene (19p2,3). [26 Histologically, the lesions feature a distinctive frondlike appearance with a stromal/smooth muscle core covered by acinar glands and normal mucosa. Nuclear atypia is absent.

Secondary complications are common and are often related to the significant numbers of hamartomas present within the bowel. Colicky abdominal pain, GI bleeding, and obstruction (frequently the result of intussusception) are widely described. [27]

Malignant transformation is reported, and other non-GI cancers may be found concomitantly.

Current surveillance recommendations for the small-bowel lesions include biannual barium upper GI series and flexible endoscopy beginning at age 10 years. [28]

Physical Examination

The physical examination is usually unrevealing, except in the case of larger tumors (>6 cm), which occasionally manifest as a palpable abdominal mass. Abdominal pain may occasionally be elicited upon palpation of the lesion. Most patients exhibit no distinct physical findings upon examination.

Differential Diagnoses



Laboratory Studies

Results from routine laboratory testing do not reveal abnormalities in most patients with small-bowel tumors. Microcytic anemia may be observed in conjunction with vascular or ulcerated bleeding lesions. Electrolyte abnormalities are not commonly identified in patients with small-bowel tumors.

Imaging Studies

Radiography

Findings from plain films of the abdomen are frequently normal. Larger lesions may demonstrate signs of complete or partial small-bowel obstruction (eg, dilated small bowel, air-fluid levels, volvulus).

Barium contrast studies (eg, upper gastrointestinal [GI] series, small-bowel enteroclysis) are the most frequently used diagnostic tools.

Images from upper GI series may demonstrate the lesion in as many as 29% of cases. The radiographic appearance on upper GI series includes the following:

  • Irregular mucosal surfaces
  • Extraluminal barium-filled cavities (showing central lesion necrosis)
  • Dumbbell-shaped lesions (indicating intraluminal and extraluminal growth)

Barium enema helps identify distal ileal lesions with successful reflux of contrast through the ileocecal valve. [29]

Selective arteriography may be used to aid in the diagnosis of possible vascular lesions and potential embolization of active bleeding. Both subserosal tumors and hemangiomas may be identified by a characteristic tumor blush visualized on arteriograms. Additional clues include multiple feeding arteries, irregular draining veins, and venous pooling around the lesion.

Arteriography may assist in differentiating malignant lesions from benign lesions. Benign tumors frequently receive arterial supply from either the gastroduodenal artery or the superior mesenteric artery. Malignant lesions often demonstrate aberrant arterial inflow from renal arteries, lumbar arteries, or both. (See the image below.)

Benign neoplasm of the small intestine. ArteriograBenign neoplasm of the small intestine. Arteriogram demonstrating small bowel gut stromal tumor, indicated by round tumor blush in lower right corner of the image.

Computed tomography

In reports, computed tomography (CT) scans of the abdomen have demonstrated as many as 27% of benign small-bowel tumors. Gut stromal tumors larger than 2 cm are frequently imaged successfully by using CT. Accurate size, evidence of ulceration, and lesion necrosis are often detected. Multidetector CT (MDCT) may be particularly useful for diagnosis and staging of small-bowel neoplasms. [30]

Bowel-wall thickening noted on abdominal CT may be caused by neoplastic, inflammatory, infectious, or ischemic conditions but may also be a normal variant. Conventional or capsule endoscopy may be considered in this setting. [31]

Ultrasonography

Ultrasonographic (US) images of the abdomen may demonstrate larger tumors (>4 cm) and can help differentiate intraluminal, intramural, and extraluminal growth patterns. [32]

Endoscopy

Upper endoscopy/intraoperative enteroscopy

Upper endoscopy has been used successfully in the detection of proximal benign small-bowel lesions in 12-30% of reported cases. For more distal small-bowel lesions, intraoperative enteroscopy is an effective technique that allows simultaneous palpation and visualization of the small bowel in its entirety to increase the possibility of lesion identification. [33]

Endoscopy allows concomitant biopsy of intraluminal lesions. Polypectomy may also be performed for small lesions.

Gut stromal tumors and lipomas frequently cannot be removed via endoscopy because of their deep intramural location and the subsequent elevated risk of bowel perforation during attempted removal. In addition, some authorities caution against endoscopic lesion biopsy because of the increased risk of shedding cells, which could lead to nests of local tumor recurrence. (See the image below.)

Benign neoplasm of the small intestine. IntraoperaBenign neoplasm of the small intestine. Intraoperative view of an ependymal small bowel stromal tumor. Notice the narrow lesion stalk and high degree of vascularity.

Capsule endoscopy

Capsule endoscopy has been successfully used to detect small-bowel lesions that have previously remained undiagnosed by other methods. [2334353637Both color video images and transit time values can be analyzed for regional mucosal abnormalities.

Solid benign tumors, such as leiomyomas, as well as vascular lesions (eg, angiodysplasia and varices), have been identified in patients through the use of capsule endoscopy.



Medical Care

In general, strict medical management currently has no role in benign small-bowel tumors. Patients with suggestive abdominal pain, particularly if associated with evidence of anemia or intermittent obstruction, should be referred for surgical evaluation and management. Asymptomatic evidence of small-bowel mass, stricture, or intermittent obstruction discovered on incidental radiographs should be referred for surgical evaluation. [38]

Surgical Care

Surgical excision remains the recommended therapy for benign small-bowel tumors. Exploratory laparotomy with excision of the lesion provides the safest and most direct method for lesion identification and treatment. Tumors discovered incidentally at laparotomy should be removed to prevent future symptom development and secondary complications.

Both segmental resection and enterotomy/polypectomy have been used for lesion removal. If the pathology cannot be established at the time of resection, full segmental resection with adequate margins is recommended. (See the image below.) The literature confirms an excellent prognosis for tumors resected prior to tumor perforation or onset of massive gastrointestinal (GI) hemorrhage. Laparoscopic, endoscopic, and robotic-assisted approaches have been described. [39404142]

Benign neoplasm of the small intestine. Cross sectBenign neoplasm of the small intestine. Cross section of a gross ependymal small bowel stromal tumor after removal. Mixed stromal elements and a high degree of cellularity are apparent.

Complications

Surgical complications for small-bowel tumor resection should be minimal and limited to the technical aspects of the operation. Intraoperative bleeding, wound infections, anastomotic leakage, and failure to localize the tumor at the time of operation have all been reported.

Postoperative complications include ileus, incisional hernia, and delayed small-bowel obstruction from adhesions. Given the limited amount of bowel commonly resected for these rare tumors, short-bowel syndrome typically is not a concern.

Activity

Activity is generally as tolerated for the patient. If the patient requires operative exploration for a benign small-bowel tumor, the postoperative activity regimen should follow the recommendation of the operative surgeon.

Consultations

Consultations with either gastroenterology or general surgery may be helpful when abdominal pain of unknown origin or suspicion of small-bowel pathology exists so that the patient may benefit from full endoscopy, capsule endoscopy, or intraoperative push enteroscopy.