Neuroendocrine neoplasms
Neuroendocrine neoplasms, also neuroendocrine tumours, are a group of tumours whose behaviour varies from benign to malignant and are found in may different sites.
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.
- May have a trabecular architecture.
- Stippled chromatin AKA salt-and-pepper chromatin, coarse chromatin.
- Classically subepithelial/mural.
DDx:
Images:
IHC - generic
Key stains:[7]
- Chromogranin A +ve.
- Considered the most specific neuroendocrine stain.[8]
- Synaptophysin +ve.
Others:
- NSE +ve.
- CD56 +ve.
- Ki-67 - useful for grading.
- PGP9.5.[8]
Hormone products:
- Glucagon +ve/-ve.
- Gastrin +ve/-ve.
- Somatostatin +ve/-ve.
Site specific
Lung
Main article: Lung_tumours#Neuroendocrine_tumours
Gastrointestinal tract
WHO classification for digestive NET
Subtypes:[9]
- Neuroendocrine tumour G1.
- Neuroendocrine tumour G2.
- Neuroendocrine carcinoma, small cell type.
- Neuroendocrine carcinoma, large cell type.
- Mixed adenoneuroendocrine carcinoma.
Grading
Grading of NETs:[10]
- 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
Divided into four types:[11]
| Tumour type | Relative prevalence | Multifocality | Tumour size | Typical location | Clinical | Other | Histology |
|---|---|---|---|---|---|---|---|
| Type 1 | ~75% | yes | small (5-10 mm) | body | benign typically, female:male ~ 4:1, 50-60 years | chronic atrophic gastritis - usu. autoimmune | WDNET, WDNEC |
| Type 2 | rare | yes | small ~15 mm | body | aggressive, ~50 years old | assoc. MEN I, hyperchlorhydia | WDNEC, WDNET |
| Type 3 | 10-15% | no | small and large | variable location | aggressive if >2.0 cm, males > females | normal gastrin levels | WDNET |
| Type 4 | extremely rare | no | large | variable location | aggressive (mets usu. at time of Dx), males > females | elevated gastrin d/t parietal cell dysfunction | PDNEC |
Notes:
- WDNET = well-differentiated neuroendocrine tumour.
- WDNEC = well-differentiated neuroendocrine carcinoma.
- PDNEC = poorly-differentiated neuroendocrine carinoma.
Duodenum
Main article: Duodenal neuroendocrine tumour
Pancreatic
Main article: Pancreatic neuroendocrine tumour
Vermiform appendix
Main article: Appendiceal neuroendocrine tumour
See also
References
- ↑ Chetty, R. (Apr 2008). "Requiem for the term 'carcinoid tumour' in the gastrointestinal tract?". Can J Gastroenterol 22 (4): 357-8. PMID 18414708.
- ↑ 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.
- ↑ 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.
- ↑ 4.0 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.
- ↑ 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.
- ↑ URL: [http://path.upmc.edu/cases/case7.html http://path.upmc.edu/cases/case7.html}. Accessed on: 17 December 2011.
- ↑ 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.
- ↑ 8.0 8.1 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.
- ↑ 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.
- ↑ 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.
- ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/StomachNET_11protocol.pdf. Accessed on: 29 March 2012.