Pancreas
Neuroendocrine neoplasms
Neuroendocrine carcinoma

Author: Sabrina Sopha, M.D. (see Authors page)

Revised: 21 October 2017, last major update October 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Pancreas neuroendocrine carcinoma [title]
Cite this page: Sopha, S. Neuroendocrine carcinoma, NOS. PathologyOutlines.com website. http://pathologyoutlines.com/topic/pancreasneuroendocrinecarcinoma.html. Accessed November 24th, 2017.
Definition / general
  • Neoplasms which express neuroendocrine markers (synaptophysin, chromogranin A, NCAM / CD56, Protein Gene Product [PGP])
    • Synaptophysin is strongly and diffusely expressed in the majority of tumors; chromogranin A is focal / patchy
    • CD56 and PGP are considered less specific
  • Site specific markers: PDX1 and ISL1
Terminology
  • Mixed adenoneuroendocrine carcinoma (MANEC) expresses both exocrine and endocrine components, each > 30%
  • Nonfunctional tumors which are < 0.5 cm are termed "pancreatic neuroendocrine microadenomas"
  • Nonfunctional tumors are not associated with a clinical hormonal syndrome but may still be associated with elevated serum hormone levels or tissue hormone expression on immunohistochemistry
    • Neoplasms which secrete pancreatic polypeptide (PP), neurotensin or ghrelin are considered nonfunctional as there is no distinct clinical hormonal syndrome
  • Functional tumors are associated with elevated serum hormone levels and a clinical hormonal syndrome
Essential features
  • Immature or finely speckled chromatin (as seen in pulmonary small cell carcinoma or AML), nuclear molding, high nucleus to cytoplasm ratio in the small cell variant of poorly differentiated neuroendocrine carcinoma, WHO Grade 3 (Am J Surg Pathol 2014;38:437)
  • Prominent nucleoli or vesicular chromatin in the large cell variant of poorly differentiated neuroendocrine carcinoma, WHO Grade 3 (Am J Surg Pathol 2014;38:437)
  • High rate of cellular turnover: high mitotic rate, high apoptotic rate
  • Retention of neuroendocrine morphology in well differentiated neuroendocrine tumor, WHO Grade 3
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
  • Well differentiated neuroendocrine tumors of WHO Grade 3 are thought to arise from lower grade neuroendocrine tumors, while neuroendocrine carcinomas of WHO Grade 3 are thought to arise from squamous carcinomas or adenocarcinomas
Diagrams / tables

Images hosted on other servers:
Missing Image

Survival curves for well differentiated PanNET G2

Grading
Prognostic factors
  • 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)
    • Well differentiated neuroendocrine tumors of WHO Grade 3 should be treated with same chemotherapy regimen as well differentiated neuroendocrine tumors of Grades 1 - 2
    • Poorly differentiated neuroendocrine carcinomas of WHO Grade 3 should be treated with more aggressive chemotherapy (platinum based) similar to pulmonary small cell carcinoma (Oncologist 2016;21:1191, Cancer Treat Rev 2016;50:61, Ann Chir Plast Esthet 1987;32:124)
Gross description
  • Tan yellow, fleshy, areas of necrosis
  • Features of malignancy: invasion of fibroadipose tissue (as satellite nodules), invasion of adjacent organs, invasion of large vessels
Gross images

Images hosted on other servers:

Small cell carcinoma

Microscopic (histologic) description
  • Well differentiated neuroendocrine tumors, WHO Grade 3: organoid architecture in solid nests, trabeculae, gyri, cords, festoons, ribbons, glandular, acinar, cribriform; retention of neuroendocrine morphology
  • 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, high apoptotic rate
Microscopic (histologic) images

Images hosted on PathOut server:

AFIP Images

Focal necrosis

Small cell carcinoma



Images hosted on other servers:

Various images

Cytology description
Cytology images

Images hosted on other servers:

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+ / SATB+ in lower GI tract, CDX2- / SATB+ in upper GI tract, both pancreas and small bowel primaries can be PAX8+
  • Leukemia / lymphoma
    • Often positive for CD3, CD20, CD45, CD79a