Small intestine & ampulla
Other malignancies
Neuroendocrine tumor

Topic Completed: 1 August 2012

Minor changes: 20 November 2020

Copyright: 2002-2021,, Inc.

PubMed Search: Neuroendocrine[title] tumor small intestine

Hanni Gulwani, M.B.B.S.
Page views in 2020: 10,370
Page views in 2021 to date: 477
Cite this page: Gulwani H. Neuroendocrine tumor. website. Accessed January 20th, 2021.
Definition / general
  • Low grade to aggressive malignancies arising from epithelial stem cells in crypts
  • Neuroendocrine G1 (NET G1) tumor
  • G cell (gastrin) tumors, associated with Zollinger-Ellison syndrome, MEN1 syndrome
  • D cell (somatostatin) tumors, associated with neurofibromatosis 1 in blacks
Clinical features
  • 50% of small bowel tumors
  • Usually adults in 50s, also children
  • Most common in ileum (including Meckel diverticulum); also jejunum and distal duodenum
  • Associated with celiac disease, bowel duplication, von Recklinghausen disease, inflammatory polyps
  • 15 - 35% are multiple
  • Slow growing but can metastasize to regional lymph nodes, liver, bone, skin, thyroid
  • Usually occur as small, dispersed nodules
  • Carcinoid syndrome in 1% (20% with widespread metastases)
  • 5 year survival: 50 - 65% (85% if confined to bowel wall vs 5% if serosal invasion)
Clinical features by site
  • Duodenum:
    • 2/3 express gastrin, 1/3 of these are associated with Zollinger-Ellison syndrome and are almost always metastatic
    • May be associated with MEN1
    • Duodenal carcinoids are less aggressive, usually don't cause death vs ampullary carcinoids (Hum Pathol 2001;32:1252)
  • Ileum:
  • Case reports
    • Surgical excision of tumor and regional lymph nodes, excise solitary liver metastases
    Gross description
    • Tumor protrudes through mucosa as small, polypoid lesion, intact or ulcerated overlying mucosa, buckling of bowel wall
    • Bright yellow after formalin fixation, mean 2 cm
    Gross images

    Contributed by Charles Yee, M.D.

    Multiple carcinoids

    Images hosted on other servers:

    Carcinoid tumors

    Microscopic (histologic) description
    • Submucosal tumor that infiltrates muscularis propria
    • Solid, insular (nesting), trabecular or glandular masses of monotonous small round cells with peripheral pallisading
    • Moderate finely granular cytoplasm, small nucleoli, salt and pepper chromatin
    • Angiolymphatic invasion common, mitotic figures rare
    • Mucin present if glandular pattern
    • Amphicrine cell pattern rare (endocrine and exocrine cells)
    • Adjacent mucosa in ileal tumors shows angiomatous polyposis (mucosal edema, capillary ectasia, muscularis mucosa hypertrophy, fibrosis / smooth muscle proliferation in lamina propria, club shaped villi, intramucosal capillary proliferation; although this is not specific for carcinoid tumors, Mod Pathol 2001;14:821)
    Microscopic (histologic) images

    Contributed by Hanni Gulwani, M.D.

    Ileal biopsy

    Images hosted on other servers:

    Carcinoid tumors

    Positive stains
    Negative stains
    Electron microscopy description
    • Well formed, membrane bound, dense core secretory granules with dense (osmophilic) cores
    Board review style question #1
    A 58 year old man with hypertension, asthma and a long history of "acid reflux" presented (at the request of multiple family members) with "skin turning yellow" and weight loss. He had a long history of noncompliance but his family became alarmed when they noticed his appearance at a recent family gathering. Imaging revealed a 1.5 cm mass obstructing the ampulla of Vater. Subsequent studies reveal elevated gastrin excretion. A mutation in which of the following genes is most likely responsible for this patient's symptoms?

    1. APC
    2. MENIN
    3. MLH1
    4. MSH2
    5. RET
    Board review style answer #1
    B. MENIN: this patient presents with symptoms of obstruction related to a duodenal carcinoid tumor. Additionally, his history of acid reflux indicates oversecretion of gastrin, likely due to a gastrinoma. Gastrinomas are often found as part of multiple endocrine neoplasia type 1 and are caused by a mutation in the MENIN gene. The syndrome is comprised of pituitary, parathyroid and pancreatic islet cell tumors.

    1. Incorrect: the autosomal dominant APC gene mutation is responsible for familial adenomatous polyposis (FAP). This condition causes multiple adenomatous polyps in the colon of affected individuals.
    1. Incorrect: MLH1 is one of the mismatch repair gene mutations that have been implicated in the development of hereditary nonpolyposis colon cancer (Lynch) syndrome. This patient's presentation is not consistent with colon cancer.
    2. Incorrect: MSH2 is one of the mismatch repair gene mutations that have been implicated in the development of hereditary nonpolyposis colon cancer (Lynch) Syndrome. This patient's presentation is not consistent with colon cancer.
    3. Incorrect: the RET proto-oncogene mutations are responsible for multiple endocrine neoplasia (MEN) type 2. Neither MEN2A nor MEN2B include gastrinoma.

    Citation: Carter: Sternberg's Diagnostic Surgical Pathology, 5th Edition, 2009

    Source: BoardVitals, 12/7/2013

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