Neuroendocrine carcinoma

Last author update: 1 July 2013
Last staff update: 12 March 2024 (update in progress)

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PubMed Search: Neuroendocrine (tumor OR carcinoma) esophagus

Feriyl Bhaijee, M.D.
Israh Akhtar, M.D.
Page views in 2024 to date: 984
Cite this page: Bhaijee F, Akhtar I. Neuroendocrine carcinoma. website. Accessed April 14th, 2024.
Definition / general
  • Epithelial neoplasm with prominent neuroendocrine differentiation
  • Pathologic spectrum from low grade neuroendocrine tumors (carcinoid, atypical carcinoid) to high grade neuroendocrine carcinoma (small cell or large cell neuroendocrine carcinoma)

Small cell neuroendocrine carcinoma:
  • Small cell neuroendocrine carcinoma is analogous to pulmonary small cell carcinoma
  • WHO definition
    • Malignant epithelial tumor consisting or small cells with scant cytoplasm, ill defined cell borders, finely granular nuclear chromatin and absent or inconspicuous nucleoi
    • Cells are round, oval and spindle shaped
    • Nuclear molding is prominent
    • Necrosis is typically extensive and the mitotic count is high
  • Synonyms
    • Neuroendocrine tumor (low grade) = carcinoid tumor, atypical carcinoid tumor
    • Neuroendocrine carcinoma (high grade) = small cell carcinoma, large cell carcinoma
  • Extremely rare in esophagus: about 100 reported cases (mostly high grade / small cell carcinomas)
  • M:F ratio = 3:1 (Am J Surg Pathol 2013;37:467)
  • Mean age: 62 years
Clinical features
  • Usually incidental / unexpected finding on radiologic studies or upper GI endoscopy
  • Dysphagia, weight loss, chest pain with high grade carcinoma (Int J Clin Exp Pathol 2013;6:485)
  • Typically diagnosed via biopsy or (less commonly) surgical resection

Small cell neuroendocrine carcinoma:
Prognostic factors
  • Mitotic rate and Ki67 index determine grade
  • Low grade lesions have favorable prognosis
  • High grade carcinomas are very aggressive, as in other body sites
Case reports

Small cell neuroendocrine carcinoma:
Gross description
  • Polypoid or ulcerated mass on upper endoscopy
Gross images

AFIP images

Bulky, ulcerated, infiltrative lesion

Images hosted on other servers:

Small cell
carcinoma (upper),
squamous cell
carcinoma (lower)

Microscopic (histologic) description
  • Well differentiated (low grade) tumors
    • Uniform, small, bland tumor cells in solid, trabecular, gyriform or glandular patterns
    • May have Paneth cell differentiation
  • Poorly differentiated (high grade) carcinomas
    • Large cell type: nests of pleomorphic, large cells with prominent nucleoli and a moderate amount of cytoplasm
    • Small cell type: sheets and nests of small cells with hyperchromatic nuclei and a minimal to moderate amount of cytoplasm; prominent crush artifact and Azzopardi phenomenon, as in small cell carcinomas at other sites
    • Necrosis
    • Increased mitotic activity
    • Angiolymphatic invasion common
  • Solid to cribriform growth
  • Usually in lamina propria
  • May be associated with heterotopic oxyntic mucosa or Barrett esophagus (large cell carcinoma)
  • Neuroendocrine carcinoma may have small component(s) of adenocarcinoma or squamous cell carcinoma differentiation
Microscopic (histologic) images

Contributed by Mark R. Wick, M.D. and AFIP images

Small cell carcinoma of esophagus

In muscularis

Small cell neuroendocrine carcinoma:

Diffusely infiltrating sheets of small cells

In situ component

Squamous cell differentiation

Cytology description
  • Low grade tumors
    • Flat sheets or loosely cohesive groups / cords of monotonously uniform plasmacytoid cells
    • Eccentric nuclei, coarsely stippled (salt and pepper) chromatin, finely granular cytoplasm
  • High grade carcinomas
    • Obvious pleomorphism, marked nuclear molding, hyperchromatic nuclei, inconspicuous nucleoli
    • Numerous mitoses, crush artifact, necrosis
    • Apoptotic figures, blue bodies
Cytology images

Contributed by Mark R. Wick, M.D.

Neuroendocrine tumor

Images hosted on other servers:

Carcinoid tumor

Small cell carcinoma

Positive stains
Negative stains
Electron microscopy images

Images hosted on other servers:

Neurosecretory granules

Differential diagnosis
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