Difference between pages "Neuroendocrine neoplasms" and "Epstein-Barr virus"

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[[Image:Small intestine neuroendocrine tumour high mag.jpg|thumb|right|200px|Micrograph of a neuroendocrine tumour of the small bowel. [[H&E stain]].]]
[[Image:Nasopharyngeal carcinoma - EBER -- very low mag.jpg |thumb|right|Micrograph showing an EBER ('''E'''pstein-'''B'''arr virus (EBV)-'''e'''ncoded small '''R'''NAs) positive [[nasopharyngeal carcinoma]]. (WC)]]
'''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'''.  
The '''Epstein-Barr virus''', abbreviated '''EBV''', is [[virus]] implicated in several types of [[cancer]].


These tumours arise from epithelium; thus, malignant tumours in this group are referred to as '''neuroendocrine carcinomas'''.
==General==
*Cases [[mononucleosis]].
*Part of the herpes group of viruses.<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/herpes.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/herpes.htm]. Accessed on: 14 April 2011.</ref>


=Use of the term ''carcinoid''=
Note:
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 }}
*The virus is ''Epstein''... the tricuspid abnormality is ''[[Ebstein anomaly|Ebstein]]''.
</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>


The term is still used for neuroendocrine tumours of the lung - see [[carcinoid tumours]].
===Associations===
Cancer:<ref name=Ref_PCPBoD8_169>{{Ref PCPBoD8|169}}</ref>
*Classical [[Hodgkin lymphoma]].
*[[Burkitt lymphoma]].
*[[Nasopharyngeal carcinoma]].
*B cell lymphomas -- in immunosuppressed individuals.
**[[Post-transplant lymphoproliferative disorder]].
*[[Leiomyoma]] and [[leiomyosarcoma]] in the context of [[HIV]].<ref name=pmid8880205>{{Cite journal  | last1 = McClain | first1 = KL. | last2 = Joshi | first2 = VV. | last3 = Murphy | first3 = SB. | title = Cancers in children with HIV infection. | journal = Hematol Oncol Clin North Am | volume = 10 | issue = 5 | pages = 1189-201 | month = Oct | year = 1996 | doi =  | PMID = 8880205 }}</ref>
*[[Extranodal NK/T-cell lymphoma, nasal type]].


=Carcinoid syndrome=
Other:
===Pathophysiology===  
*[[Hemophagocytic syndrome]].<ref name=pmid20819601>{{cite journal |author=Jin YK, Xie ZD, Yang S, Lu G, Shen KL |title=Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: a retrospective study of 78 pediatric cases in mainland of China |journal=Chin. Med. J. |volume=123 |issue=11 |pages=1426–30 |year=2010 |month=June |pmid=20819601 |doi= |url=}}</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>
*[[Epstein-Barr virus-associated smooth muscle tumour]] - very uncommon, in immunoincompetent individuals.<ref name=pmid16330945>{{Cite journal  | last1 = Deyrup | first1 = AT. | last2 = Lee | first2 = VK. | last3 = Hill | first3 = CE. | last4 = Cheuk | first4 = W. | last5 = Toh | first5 = HC. | last6 = Kesavan | first6 = S. | last7 = Chan | first7 = EW. | last8 = Weiss | first8 = SW. | title = Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients. | journal = Am J Surg Pathol | volume = 30 | issue = 1 | pages = 75-82 | month = Jan | year = 2006 | doi =  | PMID = 16330945 }}</ref>
*In GI NETs ''carcinoid syndrome'' usually only arises in the context of liver metastases.
*EBV-associated [[colitis]]<ref name=pmid19279175>{{Cite journal  | last1 = Weinberg | first1 = I. | last2 = Neuman | first2 = T. | last3 = Margalit | first3 = M. | last4 = Ayman | first4 = F. | last5 = Wolf | first5 = DG. | last6 = Ben-Yehuda | first6 = A. | title = Epstein-barr virus-related diarrhea or exacerbation of inflammatory bowel disease: diagnostic dilemma. | journal = J Clin Microbiol | volume = 47 | issue = 5 | pages = 1588-90 | month = May | year = 2009 | doi = 10.1128/JCM.02477-08 | PMID = 19279175 | url = http://jcm.asm.org/content/47/5/1588.full }}</ref> - may mimic [[IBD]].<ref name=pmid21119609>{{Cite journal  | last1 = Karlitz | first1 = JJ. | last2 = Li | first2 = ST. | last3 = Holman | first3 = RP. | last4 = Rice | first4 = MC. | title = EBV-associated colitis mimicking IBD in an immunocompetent individual. | journal = Nat Rev Gastroenterol Hepatol | volume = 8 | issue = 1 | pages = 50-4 | month = Jan | year = 2011 | doi = 10.1038/nrgastro.2010.192 | PMID = 21119609 }}</ref>
**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=
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:
*[[Paraganglioma]].
*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>).
==Images==
<gallery>
<gallery>
Image:Small_intestine_neuroendocrine_tumour_low_mag.jpg | Neuroendocrine tumour - low mag. (WC/Nephron)
File:EBV infection cycle in healthy humans.png | EBV infection cycle. (WC)
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>
</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=
==Microscopic==
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>
Features:
*Chromogranin A +ve.
*Variable - see specific pathologies in ''Associations'' section.
**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>
**+/-Atypical lymphocytes.
*Synaptophysin +ve.
**+/-Hemophagocytosis (uncommon).
 
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>
 
Hormone products:
*Glucagon +ve/-ve.
*Gastrin +ve/-ve.
*Somatostatin +ve/-ve.
 
=Site specific=
==Lung==
{{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==
===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===
Images:
{{Main|Duodenal neuroendocrine tumour}}
*[http://path.upmc.edu/cases/case526.html EBV-associated gastritis (upmc.edu)].


===Pancreatic===
==IHC==
{{Main|Pancreatic neuroendocrine tumour}}
*Mixed population of CD3 & CD20 -- in benign.


===Vermiform appendix===
==Molecular==
{{Main|Appendiceal neuroendocrine tumour}}
*EBER +ve - [[in situ hybridization]] for RNA fragments in EBV.<ref name=pmid9761938>{{Cite journal  | last1 = Tornóczky | first1 = T. | last2 = Kelényi | first2 = G. | last3 = Pajor | first3 = L. | title = EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms. | journal = Pathol Oncol Res | volume = 4 | issue = 3 | pages = 201-5 | month =  | year = 1998 | doi =  | PMID = 9761938 }}</ref>
**EBER = '''E'''pstein-'''B'''arr virus (EBV)-'''e'''ncoded small '''R'''NAs.<ref name=pmid20399962>{{cite journal |authors=Iwakiri D, Takada K |title=Role of EBERs in the pathogenesis of EBV infection |journal=Adv. Cancer Res. |volume=107 |issue= |pages=119–36 |date=2010 |pmid=20399962 |doi=10.1016/S0065-230X(10)07004-1 |url=}}</ref>


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


=References=
==References==
{{Reflist|2}}
{{Reflist|2}}


[[Category:Basics]]
[[Category:Viruses]]

Revision as of 20:28, 24 May 2020

Micrograph showing an EBER (Epstein-Barr virus (EBV)-encoded small RNAs) positive nasopharyngeal carcinoma. (WC)

The Epstein-Barr virus, abbreviated EBV, is virus implicated in several types of cancer.

General

Note:

  • The virus is Epstein... the tricuspid abnormality is Ebstein.

Associations

Cancer:[2]

Other:

  • EBV infection cycle. (WC)

Microscopic

Features:

  • Variable - see specific pathologies in Associations section.
    • +/-Atypical lymphocytes.
    • +/-Hemophagocytosis (uncommon).

Images:

IHC

  • Mixed population of CD3 & CD20 -- in benign.

Molecular

See also

References

  1. ↑ URL: http://www.meddean.luc.edu/lumen/MedEd/orfpath/herpes.htm. Accessed on: 14 April 2011.
  2. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 169. ISBN 978-1416054542.
  3. ↑ McClain, KL.; Joshi, VV.; Murphy, SB. (Oct 1996). "Cancers in children with HIV infection.". Hematol Oncol Clin North Am 10 (5): 1189-201. PMID 8880205.
  4. ↑ Jin YK, Xie ZD, Yang S, Lu G, Shen KL (June 2010). "Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: a retrospective study of 78 pediatric cases in mainland of China". Chin. Med. J. 123 (11): 1426–30. PMID 20819601.
  5. ↑ Deyrup, AT.; Lee, VK.; Hill, CE.; Cheuk, W.; Toh, HC.; Kesavan, S.; Chan, EW.; Weiss, SW. (Jan 2006). "Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients.". Am J Surg Pathol 30 (1): 75-82. PMID 16330945.
  6. ↑ Weinberg, I.; Neuman, T.; Margalit, M.; Ayman, F.; Wolf, DG.; Ben-Yehuda, A. (May 2009). "Epstein-barr virus-related diarrhea or exacerbation of inflammatory bowel disease: diagnostic dilemma.". J Clin Microbiol 47 (5): 1588-90. doi:10.1128/JCM.02477-08. PMID 19279175. http://jcm.asm.org/content/47/5/1588.full.
  7. ↑ Karlitz, JJ.; Li, ST.; Holman, RP.; Rice, MC. (Jan 2011). "EBV-associated colitis mimicking IBD in an immunocompetent individual.". Nat Rev Gastroenterol Hepatol 8 (1): 50-4. doi:10.1038/nrgastro.2010.192. PMID 21119609.
  8. ↑ Tornóczky, T.; Kelényi, G.; Pajor, L. (1998). "EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms.". Pathol Oncol Res 4 (3): 201-5. PMID 9761938.
  9. ↑ Iwakiri D, Takada K (2010). "Role of EBERs in the pathogenesis of EBV infection". Adv. Cancer Res. 107: 119–36. doi:10.1016/S0065-230X(10)07004-1. PMID 20399962.
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