Difference between revisions of "Neuroendocrine neoplasms"

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'''Neuroendocrine neoplasms''', also '''neuroendocrine tumours''', are a group of tumours whose behaviour varies from benign to malignant and are found in may different sites.
[[Image:Small intestine neuroendocrine tumour high mag.jpg|thumb|right|200px|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''=
Use of the term ''carcinoid'' is discouraged.<ref name=pmid18414708>{{Cite journal  | last1 = Chetty | first1 = R. | title = Requiem for the term 'carcinoid tumour' in the gastrointestinal tract? | journal = Can J Gastroenterol | volume = 22 | issue = 4 | pages = 357-8 | month = Apr | year = 2008 | doi =  | PMID = 18414708 }}
Use of the term ''carcinoid'' is discouraged (in pathology reports), in the context of ''[[gastrointestinal pathology]]''.<ref name=pmid18414708>{{Cite journal  | last1 = Chetty | first1 = R. | title = Requiem for the term 'carcinoid tumour' in the gastrointestinal tract? | journal = Can J Gastroenterol | volume = 22 | issue = 4 | pages = 357-8 | month = Apr | year = 2008 | doi =  | PMID = 18414708 }}
</ref><ref name=pmid15153416>{{Cite journal  | last1 = Klöppel | first1 = G. | last2 = Perren | first2 = A. | last3 = Heitz | first3 = PU. | title = The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. | journal = Ann N Y Acad Sci | volume = 1014 | issue =  | pages = 13-27 | month = Apr | year = 2004 | doi =  | PMID = 15153416 }}
</ref><ref name=pmid15153416>{{Cite journal  | last1 = Klöppel | first1 = G. | last2 = Perren | first2 = A. | last3 = Heitz | first3 = PU. | title = The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. | journal = Ann N Y Acad Sci | volume = 1014 | issue =  | pages = 13-27 | month = Apr | year = 2004 | doi =  | PMID = 15153416 }}
</ref><ref name=pmid14513276>{{cite journal |author=Klöppel G |title=[Neuroendocrine tumors of the gastrointestinal tract] |language=German |journal=Pathologe |volume=24 |issue=4 |pages=287–96 |year=2003 |month=July |pmid=14513276 |doi=10.1007/s00292-003-0636-7 |url=}}</ref>
</ref><ref name=pmid14513276>{{cite journal |author=Klöppel G |title=[Neuroendocrine tumors of the gastrointestinal tract] |language=German |journal=Pathologe |volume=24 |issue=4 |pages=287–96 |year=2003 |month=July |pmid=14513276 |doi=10.1007/s00292-003-0636-7 |url=}}</ref>
The term is still used for neuroendocrine tumours of the lung - see [[carcinoid tumours]].
=Carcinoid syndrome=
===Pathophysiology===
*Neuroendocrine tumour -> hormone secretion (5-hydroxytryptamine + others).<ref name=pmid19444261>{{Cite journal  | last1 = Druce | first1 = M. | last2 = Rockall | first2 = A. | last3 = Grossman | first3 = AB. | title = Fibrosis and carcinoid syndrome: from causation to future therapy. | journal = Nat Rev Endocrinol | volume = 5 | issue = 5 | pages = 276-83 | month = May | year = 2009 | doi = 10.1038/nrendo.2009.51 | PMID = 19444261 }}</ref>
*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.<ref name=pmid1574032>{{Cite journal  | last1 = Haq | first1 = AU. | last2 = Yook | first2 = CR. | last3 = Hiremath | first3 = V. | last4 = Kasimis | first4 = BS. | title = Carcinoid syndrome in the absence of liver metastasis: a case report and review of literature. | journal = Med Pediatr Oncol | volume = 20 | issue = 3 | pages = 221-3 | month =  | year = 1992 | doi =  | PMID = 1574032 }}</ref>
===Clinical===
Features:<ref name=pmid19444261/>
*Diarrhea, flushing and wheezing.
===Pathologic findings===
Classic pathologic finding:<ref name=pmid19444261/>
*Fibrosis of cardiac valves (tricuspid and pulmonary).
**Result ''TIPS'' = '''t'''ricuspid '''i'''nsufficiency '''p'''ulmonary '''s'''tenosis.


=Microscopic - generic=
=Microscopic - generic=
Features:
Features:
*Nests of cells.
*Nests of cells - with fibrous stroma in between.
**May have a [[trabecular]] architecture.
*Stippled chromatin [[AKA]] salt-and-pepper chromatin, coarse chromatin.
*Stippled chromatin [[AKA]] salt-and-pepper chromatin, coarse chromatin.
*Classically subepithelial/mural.
*Classically subepithelial/mural.


Images:
DDx:
*[http://commons.wikimedia.org/wiki/File:Small_intestine_neuroendocrine_tumour_low_mag.jpg Neuroendocrine tumour - low mag. (WC)].
*[[Paraganglioma]].
*[http://commons.wikimedia.org/wiki/File:Small_intestine_neuroendocrine_tumour_intermed_mag.jpg Neuroendocrine tumour - intermed. mag. (WC)].
*Neoplasm with neuroendocrine differentiation (<30% neuroendocrine component<ref name=pmid26556999>{{Cite journal  | last1 = Kleist | first1 = B. | last2 = Poetsch | first2 = M. | title = Neuroendocrine differentiation: The mysterious fellow of colorectal cancer. | journal = World J Gastroenterol | volume = 21 | issue = 41 | pages = 11740-7 | month = Nov | year = 2015 | doi = 10.3748/wjg.v21.i41.11740 | PMID = 26556999 }}</ref>).
*[http://commons.wikimedia.org/wiki/File:Small_intestine_neuroendocrine_tumour_high_mag.jpg Neuroendocrine tumour - high mag. (WC)].
 
==Images==
<gallery>
Image:Small_intestine_neuroendocrine_tumour_low_mag.jpg | Neuroendocrine tumour - low mag. (WC/Nephron)
Image:Small_intestine_neuroendocrine_tumour_intermed_mag.jpg | Neuroendocrine tumour - intermed. mag. (WC/Nephron)
Image:Small_intestine_neuroendocrine_tumour_high_mag.jpg | Neuroendocrine tumour - high mag. (WC/Nephron)
</gallery>
www:
*[http://path.upmc.edu/cases/case7/images/micro3.jpg NET met to liver (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case7.html http://path.upmc.edu/cases/case7.html}. Accessed on: 17 December 2011.</ref>
 
=IHC - generic=
Key stains:<ref name=pmid17204019>{{Cite journal  | last1 = Williams | first1 = GT. | title = Endocrine tumours of the gastrointestinal tract-selected topics. | journal = Histopathology | volume = 50 | issue = 1 | pages = 30-41 | month = Jan | year = 2007 | doi = 10.1111/j.1365-2559.2006.02570.x | PMID = 17204019 }}</ref>
*Chromogranin A +ve.
**Considered the most specific neuroendocrine stain.<ref name=pmid20182342>{{Cite journal  | last1 = McCluggage | first1 = WG. | last2 = Kennedy | first2 = K. | last3 = Busam | first3 = KJ. | title = An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. | journal = Am J Surg Pathol | volume = 34 | issue = 4 | pages = 525-32 | month = Apr | year = 2010 | doi = 10.1097/PAS.0b013e3181d1d457 | PMID = 20182342 }}</ref>
*Synaptophysin +ve.
 
Others:
*NSE +ve.
*[[CD56]] +ve.
*[[Ki-67]] - useful for grading.
*PGP9.5.<ref name=pmid20182342/>
*[[CDX2]] -ve/+ve.
**+ve suggests ileum, appendix or colon origin.<ref name=pmid22180832>{{Cite journal  | last1 = Saad | first1 = RS. | last2 = Ghorab | first2 = Z. | last3 = Khalifa | first3 = MA. | last4 = Xu | first4 = M. | title = CDX2 as a marker for intestinal differentiation: Its utility and limitations. | journal = World J Gastrointest Surg | volume = 3 | issue = 11 | pages = 159-66 | month = Nov | year = 2011 | doi = 10.4240/wjgs.v3.i11.159 | PMID = 22180832 }}</ref>
*Serotonin -ve/+ve.
**+ve suggests jejuno-ileal origin.{{fact}}
 
Hormone products:
*Glucagon +ve/-ve.
*Gastrin +ve/-ve.
*Somatostatin +ve/-ve.


=Site specific=
=Site specific=
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{{Main|Lung_tumours#Neuroendocrine_tumours}}
{{Main|Lung_tumours#Neuroendocrine_tumours}}


==GI tract===
==Genitourinary pathology==
{{Main|Duodenum#Neuroendocrine_tumours}}
{{Main|Small cell carcinoma of the prostate gland}}
{{Main|Small cell carcinoma of the urinary bladder}}
 
==Gastrointestinal tract==
===WHO classification for digestive NET===
Subtypes:<ref name=pmid21601112>{{Cite journal  | last1 = Scoazec | first1 = JY. | last2 = Couvelard | first2 = A. | title = [The new WHO classification of digestive neuroendocrine tumors]. | journal = Ann Pathol | volume = 31 | issue = 2 | pages = 88-92 | month = Apr | year = 2011 | doi = 10.1016/j.annpat.2011.01.001 | PMID = 21601112 }}</ref>
#Neuroendocrine tumour G1.
#Neuroendocrine tumour G2.
#Neuroendocrine carcinoma, small cell type.
#Neuroendocrine carcinoma, large cell type.
#Mixed adenoneuroendocrine carcinoma.
 
====Grading====
Grading of NETs:<ref name=pmid21344263>{{Cite journal  | last1 = Volante | first1 = M. | last2 = Righi | first2 = L. | last3 = Berruti | first3 = A. | last4 = Rindi | first4 = G. | last5 = Papotti | first5 = M. | title = The pathological diagnosis of neuroendocrine tumors: common questions and tentative answers. | journal = Virchows Arch | volume = 458 | issue = 4 | pages = 393-402 | month = Apr | year = 2011 | doi = 10.1007/s00428-011-1060-7 | PMID = 21344263 }}</ref>
*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===
{{Main|Gastric neuroendocrine tumour}}
 
===Duodenum===
{{Main|Duodenal neuroendocrine tumour}}
 
===Pancreatic===
{{Main|Pancreatic neuroendocrine tumour}}
 
===Vermiform appendix===
{{Main|Appendiceal neuroendocrine tumour}}


=See also=
=See also=
*[[Basics]].
*[[Basics]].
*[[Goblet cell carcinoid]].
*[[Goblet cell carcinoid]].
*[[Mixed neuroendocrine-nonneuroendocrine neoplasm]] (MiNEN).


=References=
=References=
Michael
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