Neuroendocrine neoplasms

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Micrograph of a neuroendocrine tumour of the small bowel. H&E stain.

Neuroendocrine neoplasms, also neuroendocrine tumours, are a group of tumours whose behaviour varies from benign to malignant and are found in may different sites. Neuroendocrine tumour is commonly abbreviated NET.

These tumours arise from epithelium; thus, malignant tumours in this group are referred to as neuroendocrine carcinomas.

Use of the term carcinoid

Use of the term carcinoid is discouraged (in pathology reports), in the context of gastrointestinal pathology.[1][2][3]

The term is still used for neuroendocrine tumours of the lung - see carcinoid tumours.

Carcinoid syndrome

Pathophysiology

  • Neuroendocrine tumour -> hormone secretion (5-hydroxytryptamine + others).[4]
  • In GI NETs carcinoid syndrome usually only arises in the context of liver metastases.
    • GI NETs without liver mets do not develop the syndrome due to first pass effect of the liver.
    • Exceptions to the rule -- carcinoid syndrome without liver mets: ovarian NETs, testicular NETs, bronchial NETs.[5]

Clinical

Features:[4]

  • Diarrhea, flushing and wheezing.

Pathologic findings

Classic pathologic finding:[4]

  • Fibrosis of cardiac valves (tricuspid and pulmonary).
    • Result TIPS = tricuspid insufficiency pulmonary stenosis.

Microscopic - generic

Features:

  • Nests of cells - with fibrous stroma in between.
  • Stippled chromatin AKA salt-and-pepper chromatin, coarse chromatin.
  • Classically subepithelial/mural.

DDx:

  • Paraganglioma.
  • Neoplasm with neuroendocrine differentiation (<30% neuroendocrine component[6]).

Images

www:

IHC - generic

Key stains:[8]

  • Chromogranin A +ve.
    • Considered the most specific neuroendocrine stain.[9]
  • Synaptophysin +ve.

Others:

  • NSE +ve.
  • CD56 +ve.
  • Ki-67 - useful for grading.
  • PGP9.5.[9]
  • CDX2 -ve/+ve.
    • +ve suggests ileum, appendix or colon origin.[10]

Hormone products:

  • Glucagon +ve/-ve.
  • Gastrin +ve/-ve.
  • Somatostatin +ve/-ve.

Site specific

Lung

Genitourinary pathology

Gastrointestinal tract

WHO classification for digestive NET

Subtypes:[11]

  1. Neuroendocrine tumour G1.
  2. Neuroendocrine tumour G2.
  3. Neuroendocrine carcinoma, small cell type.
  4. Neuroendocrine carcinoma, large cell type.
  5. Mixed adenoneuroendocrine carcinoma.

Grading

Grading of NETs:[12]

  • Grade 1 (G1): < 2 mitoses/2 mm^2 or < 3% Ki-67.
  • Grade 2 (G2): > 2 mitoses/2 mm^2 or > 3% Ki-67 and < 20 mitoses/2 mm^2 or < 20% Ki-67.
  • Grade 3 (G3): > 20 mitoses/2 mm^2 or > 20% Ki-67.

Notes:

  • Neuroendocrine carcinomas are G3 by definition.

Stomach

Duodenum

Pancreatic

Vermiform appendix

See also

References

  1. Chetty, R. (Apr 2008). "Requiem for the term 'carcinoid tumour' in the gastrointestinal tract?". Can J Gastroenterol 22 (4): 357-8. PMID 18414708.
  2. Klöppel, G.; Perren, A.; Heitz, PU. (Apr 2004). "The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification.". Ann N Y Acad Sci 1014: 13-27. PMID 15153416.
  3. Klöppel G (July 2003). "[Neuroendocrine tumors of the gastrointestinal tract]" (in German). Pathologe 24 (4): 287–96. doi:10.1007/s00292-003-0636-7. PMID 14513276.
  4. 4.0 4.1 4.2 Druce, M.; Rockall, A.; Grossman, AB. (May 2009). "Fibrosis and carcinoid syndrome: from causation to future therapy.". Nat Rev Endocrinol 5 (5): 276-83. doi:10.1038/nrendo.2009.51. PMID 19444261.
  5. Haq, AU.; Yook, CR.; Hiremath, V.; Kasimis, BS. (1992). "Carcinoid syndrome in the absence of liver metastasis: a case report and review of literature.". Med Pediatr Oncol 20 (3): 221-3. PMID 1574032.
  6. Kleist, B.; Poetsch, M. (Nov 2015). "Neuroendocrine differentiation: The mysterious fellow of colorectal cancer.". World J Gastroenterol 21 (41): 11740-7. doi:10.3748/wjg.v21.i41.11740. PMID 26556999.
  7. URL: [http://path.upmc.edu/cases/case7.html http://path.upmc.edu/cases/case7.html}. Accessed on: 17 December 2011.
  8. Williams, GT. (Jan 2007). "Endocrine tumours of the gastrointestinal tract-selected topics.". Histopathology 50 (1): 30-41. doi:10.1111/j.1365-2559.2006.02570.x. PMID 17204019.
  9. 9.0 9.1 McCluggage, WG.; Kennedy, K.; Busam, KJ. (Apr 2010). "An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63.". Am J Surg Pathol 34 (4): 525-32. doi:10.1097/PAS.0b013e3181d1d457. PMID 20182342.
  10. Saad, RS.; Ghorab, Z.; Khalifa, MA.; Xu, M. (Nov 2011). "CDX2 as a marker for intestinal differentiation: Its utility and limitations.". World J Gastrointest Surg 3 (11): 159-66. doi:10.4240/wjgs.v3.i11.159. PMID 22180832.
  11. Scoazec, JY.; Couvelard, A. (Apr 2011). "[The new WHO classification of digestive neuroendocrine tumors].". Ann Pathol 31 (2): 88-92. doi:10.1016/j.annpat.2011.01.001. PMID 21601112.
  12. Volante, M.; Righi, L.; Berruti, A.; Rindi, G.; Papotti, M. (Apr 2011). "The pathological diagnosis of neuroendocrine tumors: common questions and tentative answers.". Virchows Arch 458 (4): 393-402. doi:10.1007/s00428-011-1060-7. PMID 21344263.