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'''.  
'''''[[Carcinoid]]''''' is a term whose use is discouraged.


These tumours arise from epithelium; thus, malignant tumours in this group are referred to as '''neuroendocrine carcinomas'''.
These tumours arise from epithelium; thus, malignant tumours in this group are referred to as '''neuroendocrine carcinomas'''.
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=Carcinoid syndrome=
=Carcinoid syndrome=
Cause:
===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>
*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/>
Classic pathologic finding:<ref name=pmid19444261/>
*Fibrosis of cardiac valves (tricuspid and pulmonary).
*Fibrosis of cardiac valves (tricuspid and pulmonary).
**Result ''TIPS'' = '''t'''ricuspid '''i'''nsufficiency '''p'''ulmonary '''s'''tenosis.
**Result ''TIPS'' = '''t'''ricuspid '''i'''nsufficiency '''p'''ulmonary '''s'''tenosis.
Clinical features:<ref name=pmid19444261/>
*Diarrhea, flushing and wheezing.


=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:
*[[WC]]:
*[[Paraganglioma]].
**[http://commons.wikimedia.org/wiki/File:Small_intestine_neuroendocrine_tumour_low_mag.jpg Neuroendocrine tumour - low 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_intermed_mag.jpg Neuroendocrine tumour - intermed. mag. (WC)].
 
**[http://commons.wikimedia.org/wiki/File:Small_intestine_neuroendocrine_tumour_high_mag.jpg Neuroendocrine tumour - high mag. (WC)].
==Images==
*www:
<gallery>
**[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>
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=
==Lung==
==Lung==
{{Main|Lung_tumours#Neuroendocrine_tumours}}
{{Main|Lung_tumours#Neuroendocrine_tumours}}
==Genitourinary pathology==
{{Main|Small cell carcinoma of the prostate gland}}
{{Main|Small cell carcinoma of the urinary bladder}}


==Gastrointestinal tract==
==Gastrointestinal tract==
{{Main|Duodenum#Neuroendocrine_tumours}}
===WHO classification for digestive NET===
 
===WHO classification===
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>
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 G1.
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Notes:
Notes:
*Neuroendocrine carcinomas are G3 by definition.
*Neuroendocrine carcinomas are G3 by definition.
===Stomach===
{{Main|Gastric neuroendocrine tumour}}
===Duodenum===
{{Main|Duodenal neuroendocrine tumour}}


===Pancreatic===
===Pancreatic===
{{Main|Pancreatic neuroendocrine tumour}}
{{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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