Small Bowel Neoplasms
Overview/orientation page. See Small Bowel Neuroendocrine Tumors (NETs), Small Bowel Adenocarcinoma, and Gastrointestinal Stromal Tumors (GIST) for the three most significant malignant subtypes in detail. Content below is from a textbook reference chapter (Sabiston Ch50 - Infectious Enteritis & Small Bowel Neoplasms), not primary literature.
General considerations
Despite composing 75% of the length and 90% of the surface area of the GI tract, the small bowel develops relatively few primary neoplasms — less than 2% of GI malignant neoplasms. Incidence of small bowel cancer has increased ~2%/year over the past decade; an estimated 10,470 US adults were diagnosed with small bowel cancer in 2018, with ~1,450 deaths. Five-year survival for localized small bowel cancer is ~85%; for regional or distant disease, 75% and 42% respectively — reflecting the recent rise in NET incidence specifically (NETs carry a better prognosis than adenocarcinoma).
Mean age at presentation is 62 (malignant tumors) vs. ~57 (benign tumors). Geographic distribution exists, with highest cancer rates among the Maori of New Zealand and ethnic Hawaiians; incidence is particularly low in India, Romania, and other parts of Eastern Europe.
Benign neoplasms are more common at autopsy but malignant neoplasms account for 75% of symptomatic lesions leading to surgery — most benign lesions are asymptomatic incidental findings. Stromal tumors and adenomas are the most frequent benign tumors, appearing more common in the distal small bowel (though this may be somewhat misleading given the relatively short length of the duodenum). Adenocarcinoma is the most common malignant neoplasm (30–50% of malignant neoplasms); NETs account for 25–30%. Adenocarcinomas are more prevalent in the proximal small bowel; other malignant lesions are more common distally.
Risk factors and associated conditions: familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (Lynch syndrome), Peutz-Jeghers syndrome, Crohn disease, gluten- sensitive enteropathy (celiac disease), prior peptic ulcer disease, cystic fibrosis, and biliary diversion (previous cholecystectomy). Controversial contributing factors: smoking, heavy alcohol consumption (>80 g/day of ethanol), and consumption of red meat or salt-cured foods.
Molecular genetics: not as fully characterized as colorectal cancer, but KRAS mutations are commonly identified, similar to CRC. Allelic losses involving tumor suppressor genes at 5q (APC), 17p (p53), and 18q (DCC, DPC4/SMAD4) have been noted in some small bowel cancers. Approximately 15% of small intestinal adenocarcinomas show DNA mismatch repair inactivation with high microsatellite instability (MSI-H) — MSI-H is typical of small bowel carcinomas associated with celiac disease, potentially linked by aberrant CpG island methylation. Microarray analyses show a high percentage of small bowel tumors express both EGFR and VEGF, possibly contributing to carcinogenesis.
Clinical manifestations
Symptoms are often vague and nonspecific — dyspepsia, anorexia, malaise, and dull, often intermittent and colicky abdominal pain — and may be present for months to years before diagnosis. Most benign neoplasms remain asymptomatic, discovered at autopsy or as incidental findings. Of symptomatic lesions, pain (most often related to obstruction) is the most frequent complaint; obstruction from benign tumors is usually from intussusception, and benign small tumors are the most common cause of adult intussusception. Hemorrhage is the next most common symptom, usually occult, though life-threatening hemorrhage is uncommon. Malignant neoplasms almost always produce symptoms — most commonly pain and weight loss; obstruction develops in 15–35% (unlike benign-lesion intussusception, this is usually from tumor infiltration and adhesions); diarrhea with tenesmus and mucus passage may occur; GI bleeding (anemia, guaiac-positive or occasionally melena/hematochezia) occurs to varying degrees and is more common with GISTs; a palpable mass in ~10%; perforation in ~10%, usually secondary to lymphomas/sarcomas.
Diagnosis
Because of the insidious nature of many small bowel neoplasms, a high index of suspicion is required — correct preoperative diagnosis is made in only 50% of symptomatic patients in most series. Plain films may confirm obstruction but are otherwise not generally helpful. Upper GI tract follow-through yields accurate diagnosis in 53–83% of patients with malignant neoplasms. Ultrasonography has not proven effective for preoperative diagnosis. CT is particularly useful for extraluminal tumors (e.g., malignant GISTs) and cancer staging. CT enterolysis is more sensitive (~95% diagnostic accuracy); MRI enterolysis has sensitivity/specificity of 98%/97%. Flexible endoscopy may be useful, particularly for duodenal lesions, and colonoscopy can be advanced into the terminal ileum for ileal lesions. Push enteroscopy is not used routinely (may take up to 8 hours, may not visualize the entire small bowel). Double-balloon enteroscopy can be a helpful adjunct but carries perforation risk and should be reserved for cases requiring biopsy or preoperative tattoo. Capsule endoscopy may have a role, particularly for obscure bleeding (sensitivity 89–95%, specificity 75–95%). Angiography is useful for diagnosing/localizing tumors of vascular origin. Despite this range of modalities, diagnosis of a small bowel tumor is often achieved only at surgical exploration.
Benign neoplasms
Most common: benign stromal tumors, adenomas, and lipomas. When a benign tumor is identified at operation, resection is indicated since symptoms are likely to develop over time; a thorough search of the remainder of the small bowel is warranted since multiple tumors are not uncommon.
- Stromal tumors (benign GISTs): see Gastrointestinal Stromal Tumors (GIST) for full detail — GISTs are the most common benign lesions to produce symptoms (bleeding, obstruction) even though adenomas are more common in autopsy series.
- Adenomas: ~15% of all benign small bowel tumors; three primary types — true adenomas, villous
adenomas, and Brunner gland adenomas. Twenty percent of true adenomas are found in the duodenum,
30% jejunum, 50% ileum; most are asymptomatic, found incidentally. Most common presenting symptoms
are bleeding and obstruction. Villous adenomas are rare, most commonly duodenal, may be
associated with familial polyposis syndrome; both true and villous adenomas follow an
adenoma-carcinoma sequence analogous to colorectal adenomas and are considered premalignant.
Villous adenomas have a particular propensity for malignant degeneration and may be large (>5 cm);
usually noted secondary to bleeding or obstruction; malignant potential 35–55%. Treatment is
endoscopic or surgical, determined by location and adenoma type — segmental resection is the
treatment of choice in the jejunum and ileum. Duodenal adenomas occur in only 5% but frequently
cause symptoms; management planning must weigh the morbidity (20–30%) of duodenal resection by
pancreaticoduodenectomy or pancreas-preserving duodenectomy. Endoscopic ultrasound helps guide
preintervention evaluation/management planning. Endoscopic resection is a safe alternative that may
delay a more aggressive procedure, though lifelong recurrence risk after endoscopic treatment
(snare excision, argon plasma coagulation, photodynamic therapy) is ~50%. Endoscopic mucosal
resection is gaining acceptance for duodenal adenomas/Brunner gland tumors, with high success rates
even for large (>2 cm) sessile lesions, though delayed bleeding risk is ~17%. Invasive cancer or
recurrence after polypectomy necessitates a more definitive approach (e.g.,
pancreaticoduodenectomy).
- FAP-associated duodenal adenomas: occur in 50–90% of FAP patients; increasing age is an independent risk factor for adenoma development. Although neoplasms grow slowly, FAP patients carry a 5% lifetime risk of duodenal adenocarcinoma, the leading cause of cancer-related mortality in these patients — routine lifelong surveillance is a priority. Screening endoscopy (forward- and side-viewing) with biopsy of all suspicious, villous, or large (>3 cm) adenomas is performed at regular intervals, directed by the Spigelman classification (Table 50.8: points for number of polyps, polyp size, histology, degree of dysplasia; stage 0–IV). Surveillance interval by Spigelman stage (Box 50.6): stage 0 → 4 years, I → 5 years, II → 2–3 years, III → 0.5–1 year, IV → consider surgery. Endoscopic mucosal resection or surgical polypectomy for large adenomas; ablative therapy (argon beam coagulation, photodynamic therapy) has had disappointing results. High-grade dysplasia, carcinoma in situ, or Spigelman stage IV necessitates pancreaticoduodenectomy or pancreas-preserving duodenectomy.
- Brunner gland adenomas: benign hyperplastic lesions from the Brunner glands of the proximal duodenum, may mimic peptic ulcer disease symptoms; diagnosed by endoscopy/biopsy; symptomatic lesions resected (endoscopically or surgically) in an accessible region. No malignant potential — radical resection should not be used.
- Lipomas: also stromal tumors; most common in the ileum, manifest as single intramural lesions in the submucosa; occur in the 6th–7th decades, more frequent in men. Less than a third are symptomatic; the most common manifestations are obstruction and bleeding from superficial ulcerations. Treatment of choice for symptomatic lesions is excision; no malignant potential — remove only if incidentally found and resection is simple.
- Peutz-Jeghers hamartomas: occur as part of Peutz-Jeghers syndrome (see also Hamartomatous Polyposis Syndromes) — an autosomal dominant inherited syndrome of mucocutaneous melanotic pigmentation and GI polyps. Classic pigmented lesions are small (1–2 mm), brown/black spots in the circumoral face, buccal mucosa, forearms, palms, soles, digits, and perianal area. Hamartomas most commonly found in jejunum and ileum; 50% of patients also have rectal/colonic lesions, 25% gastric lesions. Most common symptom is recurrent colicky abdominal pain, usually from intermittent intussusception. Lower abdominal pain with a palpable mass reported in a third of patients. Hemorrhage from autoamputation of polyps occurs but infrequently, most commonly manifest as anemia; acute life-threatening hemorrhage is uncommon but can occur. Although once considered a purely benign disease, adenomatous changes (3–6%) and extracolonic cancers (50–90% of hamartoma patients — small intestine, stomach, pancreas, ovary, lung, uterus, breast, with small intestine the most frequent site among these sites compared to other cancer sites) have been reported. Treatment for complications is directed at bowel obstruction or persistent GI bleeding — resection limited to the segment producing complications; because of the widespread nature of intestinal involvement, cure is not possible, so extensive resection is not indicated.
- Hemangiomas: developmental malformations of submucosal proliferation of blood vessels; can occur at any GI level, jejunum most commonly affected in the small bowel. Account for 3–4% of all benign small bowel tumors; multifocal in 60% of patients. May occur as part of an inherited disorder (Osler-Weber-Rendu disease) or in the liver/lung/mucous membranes; Turner syndrome patients likely also have cavernous intestinal hemangiomas. Most common symptom is intestinal bleeding. Angiography and technetium Tc-99m red blood cell scanning are the most useful diagnostic studies. Resection of the involved segment if localized preoperatively; intraoperative transillumination/palpation may help identify a nonlocalized hemangioma.
Malignant neoplasms — overview
Population-based analyses show a steady increase in small intestine malignant neoplasm incidence over the past three decades, mirrored by a more-than-fourfold increase in NET diagnosis (2.1 to 9.3 new cases per million population) while adenocarcinoma/stromal tumor/lymphoma incidence changes were less pronounced. A large SEER/Medicare retrospective study (1992–2010) found small bowel carcinoma 5-year survival of 34.9% vs. 51.5% for colorectal cancer over the same period. Unlike colorectal cancer, chemotherapy for small bowel adenocarcinoma has not improved overall survival when matching for stage — chemotherapy with surgery has not shown an appreciable survival benefit vs. surgery alone in this population, possibly indicating overuse of adjuvant chemotherapy and highlighting the need for more novel/effective treatment strategies.
See dedicated pages: Small Bowel Neuroendocrine Tumors (NETs), Small Bowel Adenocarcinoma, Gastrointestinal Stromal Tumors (GIST).
Lymphoma
Malignant lymphomas involve the small bowel primarily or as a manifestation of systemic disease. Approximately a third of GI lymphomas occur in the small bowel; these account for up to 25% of small bowel malignant tumors in adults, and are the most common intestinal neoplasm in children <10 years. Most common in the ileum, where GALT concentration is greatest. Increased risk of primary small bowel lymphoma reported in patients with celiac disease and immunodeficient states (e.g., AIDS). Gross appearance: usually large (>5 cm), may extend beneath the mucosa; microscopically, diffuse infiltration of the intestinal wall is common. Symptoms: pain, weight loss, nausea, vomiting, change in bowel habits; perforation may occur in up to 25% of patients; fever is uncommon and suggests systemic involvement.
Treatment remains controversial. Traditionally, a combination of surgery, chemotherapy, and radiation was used for all small bowel tumors. However, in the absence of symptoms, small bowel lymphomas are often chemo-responsive and do not require surgery — this can typically be predicted by cell type: B- cell lymphomas are more chemosensitive than T-cell lymphomas and have high remission rates with or without surgery. T-cell lymphomas are traditionally more resistant to therapy and progress to obstruction/perforation symptoms if not resected. Regardless of cell type, resection is indicated at any onset of symptoms because progression to life-threatening hemorrhage or perforation portends a dismal prognosis. Five-year survival of 50–60% can be expected and is dictated by response to systemic therapy rather than by success of surgical resection.
Metastatic neoplasms
Metastatic tumors involving the small bowel are much more common than primary neoplasms. Metastases to the small bowel usually arise from other intraabdominal organs (uterine cervix, ovaries, kidneys, stomach, colon, pancreas), by direct extension or implantation of tumor cells. Metastases from extraabdominal tumors are rare but may be found in patients with breast adenocarcinoma or lung carcinoma. Cutaneous melanoma is the most common extraabdominal source to involve the small intestine, found in more than 50% of patients dying of malignant melanoma (Fig. 50.38). Common symptoms of metastatic disease include anorexia, weight loss, anemia, bleeding, and partial bowel obstruction. Treatment is often palliative to relieve symptoms, or occasionally a bypass if the metastatic tumor is extensive and not amenable to resection. Nonoperative palliation of malignant bowel obstruction includes endoscopic or radiologic placement of self-expandable metal stents, especially in patients with very poor performance status who may not tolerate a surgical procedure; gastrostomy and jejunostomy tubes may also be placed to provide decompression when other palliative methods are not possible.
Open items / gaps
- No primary literature yet in the wiki on any small bowel neoplasm subtype — content here and in the linked NET/adenocarcinoma/GIST pages is entirely textbook-reference-derived.
- Lymphoma treatment above is brief relative to its clinical importance — worth expanding if a dedicated primary-literature source is ingested later, and worth cross-linking once the wiki has a general lymphoma/hematologic malignancy section (currently out of scope for this colorectal-focused wiki).