Small Intestinal Neoplasms

Essentials of Diagnosis

• Acute gastrointestinal (GI) bleeding with hematochezia or melena

• Chronic GI blood loss resulting in fatigue and iron deficiency anemia

• Obstruction resulting in vomiting

General Considerations

• Adenocarcinoma occurs most commonly in the duodenum

• Ampullary carcinoma incidence is increased > 200-fold in patients with familial adenomatous polyposis

• Nonampullary adenocarcinoma of the small intestine: majority have metastasized at the time of diagnosis

• Lymphoma may arise primarily in the GI tract or involve it secondarily in disseminated disease

  • In the United States, primary GI lymphoma accounts for 5% of all lymphomas and 20% of small bowel malignancies

  • Most common histologic subtype is non-Hodgkin extranodal marginal zone (MALT) B cell lymphoma

  • Enteropathy-associated T cell lymphoma (EATL)

    • Appears to be increasing in incidence in the United States

    • Is associated with the diagnosis of celiac disease

  • In the Middle East, lymphoma occurs in immunoproliferative small intestinal disease

• Carcinoid tumors account for one-third of small intestinal tumors

  • Carcinoid tumors derive from neuroendocrine cells and may or may not secrete a number of hormones, including serotonin or its precursors

  • Most are malignant, though many behave in an indolent fashion

  • Even small carcinoid tumors may metastasize, usually by extension to the local lymph nodes and to the liver

  • Carcinoid syndrome occurs in < 10% of patients, usually in patients with hepatic metastasis; caused by tumor secretion of hormonal mediators

• Most malignant sarcomas arise from stromal tumors that stain positive for CD117; Kaposi sarcoma is rare except in untreated AIDS

• Most benign small bowel polyps occur singly; multiple polyps suggest a hereditary polyposis syndrome

• Small bowel adenocarcinoma in young patients or those with a family history of gastrointestinal adenocarcinomas should prompt screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome)

Symptoms and Signs

• Most small bowel cancers have already metastasized at the time of diagnosis

• Adenocarcinomas

  • Abdominal pain

  • Nausea

• Nonampullary adenocarcinoma of the small intestine

  • Obstruction

  • Acute or chronic bleeding

  • Weight loss

• Ampullary carcinoma

  • Jaundice due to common bile duct obstruction

  • Bleeding

• Primary lymphoma

  • Abdominal pain

  • Weight loss

  • Nausea and vomiting

  • Abdominal distention

  • Anemia

  • Occult blood in the stool

• Carcinoid tumors

  • Most asymptomatic

  • Carcinoids are generally indolent tumors that spread slowly

  • May present with intermittent abdominal pain, bowel obstruction, or bowel infarction

  • Manifestations of carcinoid syndrome: facial flushing, edema of the head and neck (especially with bronchial carcinoid), abdominal cramps and diarrhea, bronchospasm, cardiac lesions (pulmonary or tricuspid stenosis or regurgitation), and telangiectases

• Neuroendocrine tumors

  • Diarrhea

  • Flushing

  • Wheezing

Differential Diagnosis

• Crohn disease

Benign polyps

• Mucosal polyps: adenoma, hamartoma, hyperplastic

• Lipoma

• Benign stromal tumor (leiomyoma)

Malignant lesions

• Adenocarcinoma

• Lymphoma (primary or secondary)

• Carcinoid

• Malignant stromal tumor (sarcoma)

• Kaposi sarcoma

Laboratory Tests

• Alpha heavy chains in the serum in 70% of patients with lymphoma occurring in immunoproliferative small intestinal disease

• Hypoalbuminemia secondary to protein-losing enteropathy in lymphoma

• Serum chromogranin A is elevated in most neuroendocrine tumors, although its sensitivity for small, localized carcinoid tumors is unknown

• Urinary 5-hydroxyindoleacetic acid > 25 mg/24 h and serum serotonin elevated in advanced (usually metastatic) carcinoid tumors

Imaging Studies

• Video capsule endoscopy, CT or MR enterography or barium small bowel series usually identify small bowel tumors

• Imaging and possibly bone marrow biopsy help determine tumor stage

• Somatostatin receptor scintigraphy (OctreoScan) or gallium Ga-68 DOTATATE PET scan are routinely used in staging and can help identify disease that may benefit from treatment with somatostatin analogs

Diagnostic Procedures

• Enteroscopy to visualize and biopsy small intestinal tumors

• Endoscopic, percutaneous, or laparoscopic biopsy establishes the diagnosis of primary intestinal lymphoma

• Bone marrow biopsy and, in some cases, lymphangiography for staging of primary lymphoma

• Proctoscopy: rectal carcinoids usually detected incidentally as submucosal nodules (most often < 1 cm in size)

• Appendectomy: appendiceal carcinoids < 2 cm in size are identified in 0.3%

Medications

• Role of adjuvant chemotherapy in adenocarcinoma is unclear; if administered, chemotherapy agents active in colorectal cancer are used

• Systemic chemotherapy with or without radiation therapy for primary lymphoma with extensive disease

• Octreotide

  • Inhibits hormone secretion from carcinoid tumors

  • Can be administered subcutaneously three times a day or a long-acting intramuscular depot formulation can be administered once monthly

  • Provides dramatic relief of symptoms in 90% of patients with carcinoid syndrome for a median period of 1 year

• Conventional cytotoxic chemotherapy agents do not achieve significant responses in carcinoid tumors and have not been associated with improved outcomes

• Long-acting somatostatin analog

  • Cornerstone of therapy for patients who are symptomatic either from tumor bulk or carcinoid syndrome

  • In 90% of patients, this results in dramatic relief of symptoms of carcinoid syndrome, including diarrhea or flushing, for a median period of 1 year

  • Thereafter, many patients stop responding to octreotide

  • Options to disease progression include octreotide dose escalation or addition of everolimus

Surgery

• Surgical or endoscopic excision of symptomatic benign tumors is recommended

• Surgical resection of ampullary carcinoma is curative in up to 40%

• Curative or palliative resection of nonampullary adenocarcinoma

• Curative resection of primary intestinal lymphoma for stage IE disease

• Locoregional radiation should be considered if surgical margins are positive

• Excision of carcinoids of small intestine, appendix, rectum if < 2 cm in size and if evidence of lymphatic spread

• Advanced small intestinal carcinoid disease

  • In selected patients with hepatic-dominant disease, resection of hepatic metastases may provide dramatic improvement in carcinoid syndrome symptoms

  • Tumor debulking with liver-directed therapy (chemoembolization or radioembolization) may also provide symptomatic improvement

• More extensive cancer resection operation is warranted for carcinoid tumors > 2 cm in size since they are associated with metastasis in > 20% of appendiceal and ~10% of rectal carcinoids

• Resection of hepatic metastases for refractory carcinoid syndrome, diarrhea

Therapeutic Procedures

• Liver-directed therapy (chemoembolization, radioembolization or surgical debulking) may provide symptomatic improvement in some patients with hepatic metastases

Follow-Up

• Periodic endoscopic surveillance to detect early ampullary neoplasms

Complications

• Cardiac right-sided valvular lesions are a late manifestation of metastatic carcinoid tumors

Prognosis

• Adenocarcinoma

  • Overall, prognosis is slightly worse than for similar stage colon adenocarcinoma

• Carcinoid tumors

  • Five-year survival rates for patients with stage I and II disease are 96% and 87%, respectively

  • For resectable disease with lymph node involvement (stage III), 5-year disease-free survival is 74%

  • However, by 25 years, < 25% of patients are disease-free