Neuroendocrine tumors

Neuroendocrine tumor

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Carolina Martinez Ciarpaglini, M.D., Ph.D.

Topic Completed: 6 February 2020

Minor changes: 7 May 2021

Copyright: 2020-2021,, Inc.

PubMed Search: Neuroendocrine tumor [title] colon

Carolina Martinez Ciarpaglini, M.D., Ph.D.
Page views in 2020: 6,845
Page views in 2021 to date: 14,103
Cite this page: Martinez-Ciarpaglini C. Neuroendocrine tumor. website. Accessed October 23rd, 2021.
Definition / general
  • Well differentiated tumors demonstrating morphological and immunohistochemical neuroendocrine differentiation
Essential features
  • Well differentiated neuroendocrine tumors arising in the rectum or rarely the colon
  • May be indolent and incidental or may be large with high risk of metastasis at presentation and aggressive clinical course
  • The term comprises WHO G1, G2 and rare G3 lesions (depending on the proliferative activity)
ICD coding
  • ICD-O: 8240/3 - Neuroendocrine tumor, grade 1
  • ICD-O: 8249/3 - Neuroendocrine tumor, grade 2
  • The incidence of colorectal neuroendocrine tumors has been continuously increasing in the past few decades (incidence: 1.04 per 100,000 persons) (JAMA Oncol 2017;3:1335)
  • Colorectal neuroendocrine tumors comprise roughly 30% of carcinoid tumors in the digestive system (Cancer 2003;97:934)
  • 55% of colonic neuroendocrine tumors occur in women (J Cancer 2012;3:292)
  • Mean age of presentation 58 years (Front Oncol 2016;6:173)
  • Most frequent in rectum (94.5%), followed by colon (3.9%) (Front Oncol 2016;6:173)
  • In the colon, neuroendocrine tumors are more frequent in the cecum (69.6%), followed by sigmoid (13.0%), ascending colon (13.0%) and transverse colon (4.3%) (Arq Gastroenterol 2009;46:288)
  • Colon proper is the least common site for intestinal WD-NET
Clinical features
Prognostic factors
Case reports
Clinical images

Images hosted on other servers:

Small rectal carcinoids on colonoscopy

Gross description
  • Most colorectal neuroendocrine tumors appear as yellow or pale polypoid lesions or submucosal nodules
Microscopic (histologic) description
  • Well differentiated neuroendocrine pattern:
    • Monotonous regular cells with round or oval nuclei with salt and pepper chromatin and moderate eosinophilic granular cytoplasm
    • Organoid architecture: tumor cells arranged in nests, trabecular or insular pattern (Oncologist 2016;21:1191)
  • In some cases, nuclear pleomorphism may be encountered (endocrine atypia) but is not associated with tumor aggressiveness (Oncologist 2016;21:1191)
  • Rarely mucin secretion
  • The grading scheme is based on the proliferative rate (mitoses and Ki67 index) as follows:
    • Low grade or grade 1 (G1): mitoses ≤ 2/2 mm2 and Ki67 index < 3%
    • Intermediate grade or grade 2 (G2): mitoses 2 - 20/2 mm2 or Ki67 index 3% - 20%
    • High grade or grade 3 (G3): mitoses > 20/2 mm2 or Ki67 index > 20%
  • The mitotic count should be evaluated in a 2 mm2 hotspot area (roughly equivalent to 10 high power fields with a 40x objective lens) (Arch Pathol Lab Med 2016;140:437)
  • The Ki67 index should be estimated in at least 500 cells in the hotspot regions (Oncologist 2016;21:1191)
  • For Ki67, only strong, dark brown nuclear staining is recommended for counting (Arch Pathol Lab Med 2016;140:437)
Microscopic (histologic) images

Contributed by Carolina Martinez-Ciarpaglini, M.D., Ph.D. and Yuri Tachibana, M.D.

Polypoid neuroendocrine tumor

Organoid pattern

Synaptophysin expression

Proliferative activity

Transverse colon mass

Salt and pepper chromatin

Synaptophysin immunostaining

Rectal WD-NET

Nested pattern


Positive stains
Molecular / cytogenetics description
Sample pathology report
  • Ascending colon mass, endoscopic biopsy:
    • Well differentiated neuroendocrine tumor grade 2 (G2) (see comment)
    • Comment: There are 2 mitotic figures in 2 mm2. The Ki67 index is 5% by immunohistochemistry.
Differential diagnosis
  • Neuroendocrine carcinoma (NEC):
    • High grade tumors with poorly differentiated morphology
    • Atypical small or large cells organized in diffuse sheets with little nesting
    • Apoptotic bodies and necrosis are usually observed
    • They are G3 by definition (mitoses > 20/10 high power fields or Ki67 > 20%), however, the Ki67 index is usually > 50% (Neuroendocrinology 2016;103:139)
    • BCL2, Rb and p53 immunohistochemical staining can be useful for discriminating well differentiated neuroendocrine tumors from poorly differentiated neuroendocrine carcinoma (Arch Pathol Lab Med 2016;140:437)
Board review style question #1

    A 5 mm polyp lesion located in the ascending colon was resected. The microscopic image is shown above. Which statement is true regarding this lesion?

  1. CD56 immunostaining is more specific than synaptophysin for its diagnosis
  2. CDX2 expression may indicate the site of origin of this type of tumor
  3. The proliferative activity is not relevant in these tumors
  4. The presence / absence of necrosis is the main feature in defining the tumor grade
Board review style answer #1
B. CDX2 expression may indicate the site of origin of this type of tumor

Comment Here

Reference: Neuroendocrine tumor
Board review style question #2
    Which is the defining criterion in assessing the tumor grade in neuroendocrine tumors?

  1. Cellular atypia
  2. Organoid architecture
  3. Presence of necrosis
  4. Proliferative activity
Board review style answer #2
D. Proliferative activity

Comment Here

Reference: Neuroendocrine tumor
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