Pancreas
Neuroendocrine neoplasms
Neuroendocrine carcinoma

Author: Sabrina Sopha, M.D. (see Authors page)
Editorial Board Member Review: Raul S. Gonzalez, M.D.

Revised: 29 January 2018, last major update October 2017

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

PubMed Search: Pancreas neuroendocrine carcinoma [title]
Cite this page: Sopha, S. Neuroendocrine carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pancreasneuroendocrinecarcinoma.html. Accessed May 27th, 2018.
Definition / general
  • Poorly differentiated neoplasms with high grade morphology that convincingly express neuroendocrine markers (synaptophysin, chromogranin A, NCAM / CD56, protein gene product [PGP])
    • Synaptophysin is strongly and diffusely expressed in most lesions; chromogranin A is focal / patchy
    • CD56 and PGP are considered less specific
  • Site specific markers include PDX1 and ISL1
Terminology
  • "Neuroendocrine carcinoma" is now reserved for poorly differentiated, obviously malignant neoplasms; "neuroendocrine tumor" refers to well differentiated lesions with a "carcinoid" morphology, regardless of grade
  • Neoplasms with both neuroendocrine and nonneuroendocrine components, formerly known as MANEC (mixed adenocarcinoma and neuroendocrine carcinoma), have a WHO 2018 classification of MENEN (mixed endocrine and nonendocrine neoplasm); the neuroendocrine component may be a tumor or a carcinoma
Essential features
  • Immature or finely speckled chromatin (as seen in pulmonary small cell carcinoma or acute myeloid leukemia [AML]), nuclear molding
  • High rate of cellular turnover: high mitotic rate, high apoptotic rate
  • Small cell variant of poorly differentiated neuroendocrine carcinoma, WHO grade 3: high nucleus to cytoplasm ratio (Am J Surg Pathol 2014;38:437)
  • Large cell variant of poorly differentiated neuroendocrine carcinoma, WHO grade 3: prominent nucleoli or vesicular chromatin (Am J Surg Pathol 2014;38:437)
Epidemiology
  • Average patient age 59 years
  • Male: female ratio 1.4
  • Most poorly differentiated neuroendocrine carcinomas, WHO grade 3 are of the large cell variant (Am J Surg Pathol 2014;38:437)
Sites
Etiology
  • No known environmental factors
  • Poorly differentiated neuroendocrine carcinomas of WHO grade 3 are thought to arise from squamous carcinoma or adenocarcinoma
Diagrams / tables

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Missing Image

Survival curves for
well differentiated
tumors and carcinomas

Grading
Prognostic factors
  • Much worse prognosis than well differentiated neuroendocrine tumors
  • Ki67 index and mitotic count, as described above under WHO grading
  • Retention of neuroendocrine morphology
  • Response to chemotherapy
Treatment
  • Surgical resection is the mainstay
  • Chemotherapy (no established protocol)
Gross description
  • Tan yellow, fleshy, areas of necrosis
  • Indications of aggressive behavior: invasion of fibroadipose tissue (as satellite nodules), invasion of adjacent organs, invasion of large vessels
Gross images

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Small cell carcinoma

Microscopic (histologic) description
  • Poorly differentiated neuroendocrine carcinoma, WHO grade 3, small cell variant: immature or finely speckled chromatin (as seen in pulmonary small cell carcinoma or AML), nuclear molding, high nucleus to cytoplasm ratio in the (Am J Surg Pathol 2014;38:437)
  • Poorly differentiated neuroendocrine carcinoma, WHO grade 3, large cell variant: prominent nucleoli or vesicular chromatin (Am J Surg Pathol 2014;38:437)
  • High rate of cellular turnover (high mitotic rate and high apoptotic rate)
Microscopic (histologic) images

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AFIP images:

Focal necrosis

Small cell carcinoma



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Various images

Cytology description
  • Two patterns (small and large cell variants):
    • Small cell variant: small cells with large nuclei (high N/C ratio), nuclear molding, dark chromatin with inconspicuous nucleoli; prominent background degeneration and crush artifact with nuclear streaming
    • Large cell variant: large undifferentiated cells with bizarre forms or syncytial aggregates, irregular overlapping nuclei with prominent nucleoli, variable chromatin (fine or coarse) and abundant cytoplasm (delicate, dense or granular)
Cytology images

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Metastatic pulmonary small cell carcinoma to pancreas

Positive stains
Negative stains
Molecular / cytogenetics description
Differential diagnosis
  • High grade neuroendocrine carcinomas of other sites
    • TTF1+ in lung, TTF1+ / NKX3.1+ in prostate, CDX2+ / SATB2+ in lower GI tract, CDX2- / SATB2+ in upper GI tract, both pancreas and small bowel primaries can be PAX8+
  • Leukemia / lymphoma
    • Often positive for CD3, CD20, CD45, CD79a
Board review question #1
Which of the following statements concerning neuroendocrine neoplasms of the pancreas and GI tract is false?

  1. Apoptosis is a feature not considered in the WHO classification.
  2. Molecular features of poorly differentiated neuroendocrine tumors, WHO grade 3 are similar to those of poorly differentiated neuroendocrine carcinomas, WHO grade 3 (inactivation of p53, Rb / p16 or SMAD4).
  3. Molecular features of poorly differentiated neuroendocrine tumors, WHO grade 3 are similar to those of well differentiated neuroendocrine tumors, WHO grades 1 - 2 (loss of DAXX or ATRX).
  4. Neuroendocrine neoplasms which retain neuroendocrine morphology and show a Ki67 proliferation index of 20 - 50% are now classified as poorly differentiated neuroendocrine tumors, WHO grade 3.
  5. Similar to the lung, both large and small cell variants exist.
Board review answer #1
B. Molecular features of poorly differentiated neuroendocrine tumors, WHO grade 3 are similar to those of poorly differentiated neuroendocrine carcinomas, WHO grade 3 (inactivation of p53, Rb / p16 or SMAD4).