Large cell neuroendocrine carcinoma

Author: Elliot Weisenberg, M.D. (see Authors page)

Revised: 22 January 2018, last major update October 2013

Copyright: (c) 2003-2018,, Inc.

PubMed Search: Large cell neuroendocrine carcinoma esophagus

Cite this page: Weisenberg, E. Large cell neuroendocrine carcinoma. website. Accessed December 16th, 2018.
Definition / general
  • Poorly differentiated neoplasm composed of medium to large cells with neuroendocrine differentiation arising in esophagus
  • Per WHO criteria, at least 70% neuroendocrine tumor
  • Tumors with at least 30% adenocarcinoma (rarely squamous) and 30% neuroendocrine carcinoma are classified as Mixed AdenoNeuroEndocrine Carcinoma (MANEC)
  • Exceedingly rare
  • Strong male predominance
  • Cases reported 3 - 82 years but most 50 - 69 years old
  • Most in lower esophagus
  • MANEC may be associated with Barrett esophagus and adenocarcinoma (very rarely squamous cell carcinoma)
  • However, paucity of cases makes hypothesis of relationship only speculative
  • Arise from endocrine cells in esophagus (more common in distal esophagus)
Clinical features
  • Highly aggressive
  • Usually metastasis on presentation
  • Survival usually months
  • Endoscopic biopsy
Case reports
  • Surgical debulking, radiation, chemotherapy but response poor
Gross description
  • Large, exophytic ulcerated masses, usually > 5 cm
Microscopic (histologic) description
  • Solid nests or acinar structures
  • Cells medium to large size
  • Low N:C ratio, often abundant cytoplasm
  • Vesicular chromatin, visible nucleoli
  • Foci of necrosis
  • Many mitotic figures
Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Dr. Mark R. Wick:

In muscularis

Images hosted on other servers:

Collision tumor

Rosette formation

Synaptophysin, CD57

Cytology description
  • Same as large cell neuroendocrine carcinoma at other sites
Cytology images

Images hosted on PathOut server:

Images contributed by Dr. Mark R. Wick:
Electron microscopy description
  • Membrane bound neurosecretory granules
Electron microscopy images

Images hosted on other servers:

Desmosomal intercellular junctions

Differential diagnosis