Larynx, hypopharynx & trachea

Other malignancies

Neuroendocrine carcinoma

Topic Completed: 1 November 2013

Minor changes: 3 March 2021

Copyright: 2002-2021,, Inc.

PubMed Search: Neuroendocrine carcinoma [title] larynx

Nat Pernick, M.D.
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Cite this page: Pernick N. Neuroendocrine carcinoma. website. Accessed December 8th, 2021.
Definition / general
  • Difficult to distinguish paraganglioma, carcinoid and small cell carcinoma in small biopsies without stains
  • Neuroendocrine carcinomas are most common nonsquamous carcinoma of larynx
  • Preferred terminology: well differentiated, moderately differentiated and poorly differentiated (small or large cell type) neuroendocrine carcinoma for carcinoid, atypical carcinoid, small cell undifferentiated and large cell undifferentiated carcinoma (Mod Pathol 2002;15:264)
  • Usually men ages 50 - 70 years, 2/3 are heavy smokers
  • Usually supraglottic
  • 43% have lymph nodal metastases
  • Moderately differentiated neuroendocrine carcinoma (atypical carcinoid):
    • May be most common nonsquamous malignancy of larynx
    • Usually elderly male cigarette smokers
    • Clearly malignant and more aggressive than atypical carcinoids at other sites, so term "atypical carcinoid" may mislead clinicians
    • 5 year survival 48%; 10 year survival 30%; after follow up, 43% have nodal metastases, 22% have metastases to skin or subcutaneous tissue and 44% have distant spread
    • Usually supraglottic, often on arytenoid cartilage
  • Well differentiated neuroendocrine carcinoma (carcinoid tumor):
    • Rare; < 20 cases described
    • Usually supraglottic larynx, often near arytenoid or aryepiglottic fold
    • In one study, 1 of 13 died of disease, although may have metastases to liver, bone, lymph node and skin with prolonged survival
Prognostic factors
  • Poor prognostic factors: cervical nodal metastases, positive margins and vascular invasion
Case reports
  • Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) in 2 patients causing death 13 and 33 months after diagnosis (Arch Pathol Lab Med 1992;116:253)
  • Moderately differentiated neuroendocrine carcinoma (atypical carcinoid): surgical resection; not radiation sensitive
Gross description
  • Polypoid lesions 2 mm to 4 cm, arising in submucosa
Microscopic (histologic) description
  • Large polyhedral cells with hyperchromatic nuclei
  • Also anaplastic cells, areas of necrosis and mitotic figures
  • Moderately differentiated neuroendocrine carcinoma (atypical carcinoid):
    • Usually nests or sheets of epithelioid cells with round / oval nuclei (often with peripheral palisading), stippled chromatin, occasional nucleoli and variable hyperchromasia
    • More pleomorphism, mitotic figures and infiltration than well differentiated neuroendocrine tumors
    • Often mixed with other forms of carcinoma
  • Well differentiated neuroendocrine carcinoma (carcinoid tumor):
    • Nests and cords of relatively uniform cells with salt and pepper chromatin
    • May have oncocytic cells, clear cells, spindle cells
Positive stains
Negative stains
  • Moderately differentiated neuroendocrine carcinoma (atypical carcinoid): TTF1 (positive in only 13%)
Electron microscopy description
  • Dense core neurosecretory granules
Additional references
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