Esophagus

Carcinoma

Neuroendocrine carcinoma


Editorial Board Member: David J. Escobar, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Gillian L. Hale, M.D., M.P.H.

Last author update: 13 May 2024
Last staff update: 13 May 2024

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Neuroendocrine carcinoma

Gillian L. Hale, M.D., M.P.H.
Cite this page: Hale G. Neuroendocrine carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/esophagusneuroendocrine.html. Accessed December 22nd, 2024.
Definition / general
  • Rare, high grade epithelial tumor with neuroendocrine differentiation divided into small cell or large cell types by morphology; follows an aggressive clinical course and has a poor prognosis
Essential features
  • Rare malignant tumor of the esophagus with poor prognosis and frequent locoregional or distant metastasis at the time of diagnosis
  • Usually involves middle or distal third of the esophagus
  • Positive for either synaptophysin or chromogranin
  • Divided into either small cell or large cell type by morphology, using the same criteria as for other sites in the gastrointestinal tract
    • Small cell: minimal cytoplasm, nuclei with fine chromatin and nuclear molding, inconspicuous nucleoli, frequent mitoses, necrosis
    • Large cell: moderately abundant cytoplasm, nuclei with clumped chromatin and prominent nucleoli, frequent mitoses, necrosis
Terminology
  • Poorly differentiated endocrine carcinoma, small cell carcinoma, large cell carcinoma
ICD coding
  • ICD-10: C7A.1 - malignant poorly differentiated neuroendocrine tumors
  • ICD-11
    • XH0U20 - neuroendocrine carcinoma, NOS
    • 2B70.Y - other specified malignant neoplasms of esophagus
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
Diagnosis
Laboratory
  • Testing for calcium, phosphate, alkaline phosphatase can aid in evaluating for bone metastasis
  • High grade carcinomas are often nonfunctional; therefore, serum marker testing is not recommended (J Med Case Rep 2023;17:144)
Radiology description
Prognostic factors
Case reports
Treatment
  • No standardized treatment
  • Multimodal therapy (surgery, platinum based chemotherapy or radiation) improves survival in patients with locoregional and metastatic disease (Dis Esophagus 2014;27:152)
  • Folinic acid, fluorouracil and irinotecan (FOLFIRI) can be considered for second line therapy after platinum etoposide first line chemotherapy (Lancet Oncol 2023;24:297)
Clinical images

Images hosted on other servers:
Endoscopic findings

Endoscopic findings

Gross description
Gross images

AFIP images
Bulky, ulcerated, infiltrative lesion

Bulky, ulcerated, infiltrative lesion



Images hosted on other servers:
Small cell carcinoma (upper); squamous cell carcinoma (lower)

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

Microscopic (histologic) description
  • Poorly differentiated (high grade) carcinomas
  • Divided into small cell or large cell types according to WHO 2019 classification
    • Small cell carcinoma
      • Small round to oval cells with scant cytoplasm, prominent nuclear molding, fine granular chromatin, absent or inconspicuous nucleoli
      • Solid, rosette or palisading pattern of infiltration
      • Brisk mitotic activity and necrosis
    • Large cell carcinoma
      • Medium to large tumor cells with enlarged nuclei, prominent nucleoli and moderately abundant basophilic cytoplasm
      • Brisk mitotic activity and necrosis
  • Neuroendocrine carcinoma may have small component(s) of adenocarcinoma or squamous cell carcinoma differentiation (Arq Gastroenterol 2017;54:4)
Microscopic (histologic) images

Contributed by Gillian L. Hale, M.D., M.P.H., Mark R. Wick, M.D. and AFIP
Sheets of tumor cells with central necrosis

Sheets of tumor cells with central necrosis

Large cells with prominent nucleoli and numerous mitoses

Large cells with
prominent nucleoli
and numerous
mitoses

Diffusely infiltrating sheets of small cells Diffusely infiltrating sheets of small cells

Diffusely infiltrating sheets of small cells

In muscularis

In muscularis


In situ component

In situ component

Squamous cell differentiation

Squamous cell differentiation

Pancytokeratin immunostain

Pancytokeratin immunostain

Synaptophysin immunostain

Synaptophysin immunostain

Chromogranin immunostain

Chromogranin immunostain

Cytology description
  • Small cell type: obvious pleomorphism, marked nuclear molding, hyperchromatic nuclei, inconspicuous nucleoli
  • Large cell type: pleomorphic, medium to large cells, moderate cytoplasm, coarse chromatin, prominent nucleoli
  • Numerous mitoses, crush artifact, necrosis
  • Apoptotic figures, blue bodies
  • References: Cancer 2000;90:148, Mod Pathol 1992;5:555
Cytology images

Contributed by Yale Rosen, M.D.
Small cell carcinoma

Small cell carcinoma

Positive stains
Negative stains
Electron microscopy description
  • Neurosecretory granules
Electron microscopy images

Images hosted on other servers:
Neurosecretory granules

Neurosecretory granules

Molecular / cytogenetics description
  • Associated with a high rate of inactivating mutations in 5 well known genes (TP53, RB1, NOTCH1, FAT1, FBXW7) and 3 genes not previously associated with esophageal carcinogenesis (PDE3A, PTPRM and CBLN2) (Cell Res 2018;28:771)
Sample pathology report
  • Esophagus, mass, biopsy:
    • Poorly differentiated neuroendocrine carcinoma, small cell type (see comment)
    • Comment: Sections show sheets of crowded tumor cells with round to oval nuclei, inconspicuous nucleoli, prominent nuclear molding and numerous mitoses. There are broad zones of necrosis and necroinflammatory debris within the tumor. The tumor cells are highlighted by stains for pankeratin (strong, diffuse), synaptophysin (strong, diffuse) and chromogranin A (weak, patchy). Ki67 highlights a proliferative index of > 80%. The morphologic features and immunophenotype are those of a poorly differentiated neuroendocrine carcinoma, small cell type.
Differential diagnosis
Board review style question #1

For the lower esophageal tumor depicted in the image above, which of the following statements is true?

  1. Synaptophysin immunohistochemistry has greater sensitivity than chromogranin in detection
  2. There are established consensus guidelines on the treatment of this large cell carcinoma
  3. This tumor has a favorable prognosis with a median survival of 10 years
  4. Tumors with a concomitant adenocarcinoma or squamous cell carcinoma component have a worse prognosis
Board review style answer #1
A. Synaptophysin immunohistochemistry has greater sensitivity than chromogranin in detection. This is an esophageal small cell carcinoma, which expresses synaptophysin or chromogranin, although synaptophysin has greater sensitivity than chromogranin. Answer C is incorrect because this tumor has a poor prognosis. Answer D is incorrect because tumors with an adenocarcinoma or squamous cell carcinoma component tend to have a better prognosis than pure small cell carcinoma. Answer B is incorrect because the image depicts a small cell carcinoma (not large cell carcinoma) and there is no consensus approach to the treatment of neuroendocrine carcinomas given the rarity of the tumor and lack of randomized controlled trials; however, treatment often includes a combination of approaches including surgery, platinum based chemotherapy and radiation.

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Reference: Neuroendocrine carcinoma
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