Anus & perianal area


Neuroendocrine carcinoma

Editorial Board Member: Xiaoyan Liao, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Raul S. Gonzalez, M.D.

Last author update: 22 May 2023
Last staff update: 22 May 2023

Copyright: 2002-2023,, Inc.

PubMed Search: Neuroendocrine carcinoma

Raul S. Gonzalez, M.D.
Page views in 2022: 1,651
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Cite this page: Gonzalez RS. Neuroendocrine carcinoma. website. Accessed June 9th, 2023.
Definition / general
  • Poorly differentiated neuroendocrine carcinoma arising in the anus
Essential features
  • Rare, primary neuroendocrine carcinoma of the anus
  • Very aggressive, with early metastatic spread; 5 year survival is ~10%
  • Similar histology to small cell or large cell neuroendocrine carcinoma at other sites
ICD coding
  • ICD-10: C21.0 - malignant neoplasm of anus, unspecified
Clinical features
  • Tissue sampling
Radiology description
  • Destructive lesion; no features specific to neuroendocrine nature
Radiology images

Images hosted on other servers:


PET scan

PET scan

Metastatic disease

Metastatic disease

Prognostic factors
  • Higher stage confers poor prognosis
Case reports
  • Chemotherapy (often platinum based) and radiation
Microscopic (histologic) description
  • Small cell neuroendocrine carcinoma: poorly differentiated malignancy composed of solid nests of small cells with minimal cytoplasm, hyperchromatic nuclei with molding, central necrosis and high mitotic activity; resembles pulmonary counterpart
  • Large cell neuroendocrine carcinoma: poorly differentiated malignancy composed of solid nests of large cells with abundant cytoplasm, vesicular nuclei with prominent nucleoli, central necrosis and high mitotic activity
  • May have overlying squamous cell carcinoma in situ or a squamous cell carcinoma component (namely, mixed neuroendocrine - nonneuroendocrine neoplasm) (Pathol Int 2012;62:356)
  • No longer graded using WHO criteria, as it is essentially always high grade (mitotic rate > 20/2 square mm; Ki67 index > 20%)
Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.
Small cell carcinoma Small cell carcinoma

Small cell carcinoma

Large cell carcinoma Large cell carcinoma

Large cell carcinoma

Positive stains
Negative stains
  • CDX2 is negative in anal small cell carcinoma but positive in rectal small cell carcinoma
  • Squamous markers (p40, CK5) should be negative but could show focal positivity
Molecular / cytogenetics description
Sample pathology report
  • Anus, mass, biopsy:
    • Small cell neuroendocrine carcinoma (see comment)
    • Comment: The carcinoma is positive for synaptophysin and chromogranin by immunohistochemistry. Neuroendocrine carcinomas are high grade by definition.
Differential diagnosis
  • Basaloid squamous cell carcinoma:
    • Negative for neuroendocrine markers
  • Colorectal small cell carcinoma:
    • May extend into anus
    • Usually CDX2 positive
  • Basal cell carcinoma:
    • No necrosis, lower mitotic activity
    • Arises in perianal skin rather than anus
  • Well differentiated neuroendocrine tumor:
    • Rare in anus
    • Has carcinoid-like appearance, with no necrosis and few mitotic figures
  • Poorly differentiated carcinoma, NOS:
    • May resemble neuroendocrine carcinoma histologically but is negative for neuroendocrine markers
    • Also no compelling evidence of glandular or squamous differentiation
Board review style question #1

This primary anal lesion is positive for pankeratin. What other stain would be expected to be positive?

  1. CD45
  2. CDX2
  3. Napsin A
  4. Synaptophysin
Board review style answer #1
D. Synaptophysin. Anal small cell carcinoma, like all neuroendocrine carcinomas, is positive for synaptophysin. CD45 is positive in hematolymphoid neoplasms, CDX2 is positive in glandular rectal lesions and napsin A is positive in lung adenocarcinoma.

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Reference: Anus & perianal area - Neuroendocrine carcinoma
Board review style question #2
Which of the following is true about neuroendocrine carcinoma of the anus?

  1. It has a good prognosis
  2. It is associated with HPV infection
  3. It is the most common anal malignancy
  4. It shows morphologic features unique to this site
Board review style answer #2
B. It is associated with HPV infection. High risk HPV is usually detectable in anal neuroendocrine carcinoma, though at low copy numbers. This malignancy is rare and aggressive. Morphologically, it is indistinguishable from neuroendocrine carcinoma arising at other sites.

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Reference: Anus & perianal area - Neuroendocrine carcinoma
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