Difference between revisions of "Viruses"

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This article deals with '''viruses'''.  The more general topic of infective things is dealt with in [[microorganisms]].
This article deals with '''viruses'''.  The more general topic of infective things is dealt with in [[microorganisms]].
Many viruses afflict humans.  Only a few of them can be diagnosed histologically.
Many viruses afflict humans.  Only a few of them can be diagnosed histologically. 
 
[[cancer viruses|Several viruses cause cancer]] and seen directly or indirectly by pathologists frequently.


==Viral inclusions - types==
==Viral inclusions - types==
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==Human papillomavirus==
==Human papillomavirus==
*Abbreviated ''HPV''.
*Abbreviated ''HPV''.
 
{{Main|Human papillomavirus}}
===General===
*Sexually transmitted.
 
Note:
*Some tests can be done on formalin-fixed, paraffin-embedded tissue.<ref name=pmid21128780>{{Cite journal  | last1 = Black | first1 = CC. | last2 = Bentley | first2 = HA. | last3 = Davis | first3 = TH. | last4 = Tsongalis | first4 = GJ. | title = Use of a linear array for the detection of human papillomavirus genotypes in head and neck cancer. | journal = Arch Pathol Lab Med | volume = 134 | issue = 12 | pages = 1813-7 | month = Dec | year = 2010 | doi = 10.1043/2009-0592-OAR.1 | PMID = 21128780 }}</ref>
 
====Associated pathology====
*Benign:
**[[Verruca vulgaris]].
**[[Condyloma acuminatum]].
**[[Esophagus#Human_papilloma_virus_esophagitis|HPV esophagitis]].
*Malignant:
*#[[Uterine cervix|Cervical cancer]] and precursors ([[LSIL]], [[HSIL]]).
*#Anal cancer and precursors ([[Anus#Anal_intraepithelial_neoplasia|AIN]]).<ref name=pmid21616117>{{Cite journal  | last1 = Borget | first1 = I. | last2 = Abramowitz | first2 = L. | last3 = Mathevet | first3 = P. | title = Economic burden of HPV-related cancers in France. | journal = Vaccine | volume = 29 | issue = 32 | pages = 5245-9 | month = Jul | year = 2011 | doi = 10.1016/j.vaccine.2011.05.018 | PMID = 21616117 }}</ref>
*#[[Vulva|Vulvar cancer]].<ref name=pmid21616117/>
*#[[Vagina|Vaginal cancer]].<ref name=pmid21616117/>
*#[[Penis|Penile cancer]].<ref name=pmid21616117/>
*#[[HPV-associated head and neck squamous cell carcinoma]] - oropharynx (specifically - tonsils, base of tongue).
*#[[Human papillomavirus-related carcinoma with adenoid cystic-like features]].
**Possibly esophageal carcinoma<ref name=pmid21130683>{{Cite journal  | last1 = Zhang | first1 = QY. | last2 = Zhang | first2 = DH. | last3 = Shen | first3 = ZY. | last4 = Xu | first4 = LY. | last5 = Li | first5 = EM. | last6 = Au | first6 = WW. | title = Infection and integration of human papillomavirus in esophageal carcinoma. | journal = Int J Hyg Environ Health | volume = 214 | issue = 2 | pages = 156-61 | month = Mar | year = 2011 | doi = 10.1016/j.ijheh.2010.11.001 | PMID = 21130683 }}</ref> - disputed.<ref name=pmid21169053>{{Cite journal  | last1 = Iyer | first1 = A. | last2 = Rajendran | first2 = V. | last3 = Adamson | first3 = CS. | last4 = Peng | first4 = Z. | last5 = Cooper | first5 = K. | last6 = Evans | first6 = MF. | title = Human papillomavirus is detectable in Barrett's esophagus and esophageal carcinoma but is unlikely to be of any etiologic significance. | journal = J Clin Virol | volume = 50 | issue = 3 | pages = 205-8 | month = Mar | year = 2011 | doi = 10.1016/j.jcv.2010.11.015 | PMID = 21169053 }}</ref>
 
====Oncocytic types====
Known as "high risk" types; this grouping includes:<ref name=pmid22312235>{{Cite journal  | last1 = Ntova | first1 = CK. | last2 = Kottaridi | first2 = C. | last3 = Chranioti | first3 = A. | last4 = Spathis | first4 = A. | last5 = Kassanos | first5 = D. | last6 = Paraskevaidis | first6 = E. | last7 = Karakitsos | first7 = P. | title = Genetic Variability and Phylogeny of High Risk HPV Type 16, 18, 31, 33 and 45 L1 Gene in Greek Women. | journal = Int J Mol Sci | volume = 13 | issue = 1 | pages = 1-17 | month =  | year = 2012 | doi = 10.3390/ijms13010001 | PMID = 22312235 }}</ref>
*HPV 18 - predominantly adenocarcinoma.<ref name=pmid15551313>{{Cite journal  | last1 = De Boer | first1 = MA. | last2 = Peters | first2 = LA. | last3 = Aziz | first3 = MF. | last4 = Siregar | first4 = B. | last5 = Cornain | first5 = S. | last6 = Vrede | first6 = MA. | last7 = Jordanova | first7 = ES. | last8 = Fleuren | first8 = GJ. | title = Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries. | journal = Int J Cancer | volume = 114 | issue = 3 | pages = 422-5 | month = Apr | year = 2005 | doi = 10.1002/ijc.20727 | PMID = 15551313 }}</ref>
**'''Eigh'''teen = '''a'''denocarcinoma.
*HPV 16 - predominantly squamous cell carcinoma.<ref name=pmid15551313/>
**'''S'''ixteen = '''s'''quamous.
*HPV 31.
*HPV 33.
*HPV 45.
 
====Oncogenesis====
Quick & dirty explanation of pathogenesis:<ref name=pmid12445661>{{Cite journal  | last1 = Münger | first1 = K. | last2 = Howley | first2 = PM. | title = Human papillomavirus immortalization and transformation functions. | journal = Virus Res | volume = 89 | issue = 2 | pages = 213-28 | month = Nov | year = 2002 | doi =  | PMID = 12445661 }}</ref><ref name=Ref_PCPBoD8_169>{{Ref PCPBoD8|169}}</ref>
*Virus integrates into host genome.
**This is accompanied by loss of ''viral gene E2'' (which suppresses function of E6 & E7).
*''Viral gene E6'' dysregulates ''p53''.
*''Viral gene E7'' dysregulates ''RB''.
 
====Vaccine====
Recombinant vaccine (Gardasil, Silgard) - covers:<ref name=pmid21942919>{{Cite journal  | last1 = McCormack | first1 = PL. | last2 = Joura | first2 = EA. | title = Spotlight on Quadrivalent Human Papillomavirus(Types 6, 11, 16, 18) Recombinant Vaccine(Gardasil®) in the Prevention of PremalignantGenital Lesions, Genital Cancer, and Genital Warts in Women†. | journal = BioDrugs | volume = 25 | issue = 5 | pages = 339-43 | month = Oct | year = 2011 | doi = 10.2165/11205060-000000000-00000 | PMID = 21942919 }}</ref>
*HPV 6.
*HPV 11.
*HPV 16.
*HPV 18.
 
===Microscopic===
Features:
*Koilocytes:
** Perinuclear clearing.
** Nuclear changes.
*** Size similar (or larger) to those in the basal layer of the epithelium.
*** Nuclear enlargement should be evident on low power, i.e. 25x.
*** Central location - nucleus should be smack in the middle of the cell.
 
Images:
*[http://commons.wikimedia.org/w/index.php?title=File:Low-grade_squamous_intraepithelial_lesion.jpg LSIL (WC)].
*[http://commons.wikimedia.org/wiki/File:Low-grade_sil_and_endocx.jpg LSIL & endocervix (WC)].
 
===IHC===
*p16 +ve -- stains most cells infected by HPV.


==Adenovirus==
==Adenovirus==
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==Epstein-Barr virus==
==Epstein-Barr virus==
*Abbreviated ''EBV''
{{Main|Epstein-Barr virus}}
===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>
 
Note:
*The virus is ''Epstein''... the tricuspid abnormality is ''[[Ebstein anomaly|Ebstein]]''.
 
====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]].
 
Other:
*[[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>
*[[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>
*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>
 
<gallery>
File:EBV infection cycle in healthy humans.png | EBV infection cycle. (WC)
</gallery>
 
===Microscopic===
Features:
*Variable - see specific pathologies in ''Associations'' section.
**+/-Atypical lymphocytes.
**+/-Hemophagocytosis (uncommon).
 
Images:
*[http://path.upmc.edu/cases/case526.html EBV-associated gastritis (upmc.edu)].
 
===IHC===
*Mixed population of CD3 & CD20 -- in benign.
 
===Molecular===
*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>


==Polyomavirus==
==Polyomavirus==
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==Human herpesvirus-8==
==Human herpesvirus-8==
*Commonly abbreviated ''HHV-8''.
{{Main|Human herpesvirus-8}}
 
===General===
Associated with a number of cancers:
*[[Kaposi sarcoma]].
*Primary effusion lymphoma.
*Body cavity lymphoma.
*[[DLBCL|LBCL]] arising in HHV-8 associated multicentric [[Castleman disease]].
 
Other:
*[[Castleman disease]], plasma cell variant.
 
===Microscopic===
*No light microscopic changes.
 
===IHC===
*Usually HHV-8 +ve.


==West Nile virus==
==West Nile virus==
Line 275: Line 161:
*Causes ''Measles''.
*Causes ''Measles''.
**Should '''not''' be confused with ''Rubella'' ([[AKA]] ''German measles'').   
**Should '''not''' be confused with ''Rubella'' ([[AKA]] ''German measles'').   
*Uncommon due to widespread MMR vaccine.  
*Uncommon due to widespread MMR vaccine.
**However increasing in the last years most likely due to insufficient vaccination.
*May develop weeks to years after infection.  
*Illness may be complicated by ''subacute sclerosing panencephalitis'' (SSPE) - a chronic neurodegenerative condition.<ref>URL: [http://path.upmc.edu/cases/case595/dx.html http://path.upmc.edu/cases/case595/dx.html]. Accessed on: 26 January 2012.</ref>
*Illness may be complicated by ''subacute sclerosing panencephalitis'' (SSPE) - a chronic neurodegenerative condition.<ref>URL: [http://path.upmc.edu/cases/case595/dx.html http://path.upmc.edu/cases/case595/dx.html]. Accessed on: 26 January 2012.</ref>


Line 283: Line 171:
**Glassy (pink) nucleus.
**Glassy (pink) nucleus.
*Lymphocytes and macrophages (microglial cells).
*Lymphocytes and macrophages (microglial cells).
**May be mild in in measles inclusion body encephalitis.
*Multinucleated cells.
*Microglial nodules.
*Demyelination.
*Demyelination.
*Gliosis.


Notes:
Notes:

Latest revision as of 15:43, 9 December 2021

This article deals with viruses. The more general topic of infective things is dealt with in microorganisms. Many viruses afflict humans. Only a few of them can be diagnosed histologically.

Several viruses cause cancer and seen directly or indirectly by pathologists frequently.

Viral inclusions - types

Cowdry types:[1]

  • Cowdry type A inclusion:[2]
    • Round eosinophilic material surrounded by a clear halo.
  • Cowdry type B inclusion:[3]
    • Neuropathology thingy. (???)

Images:

Viruses

Herpes simplex virus

In the context of gynecologic cytopathology see: Gynecologic_cytopathology#Herpes_simplex_virus.
  • Abbreviated HSV.

General

Several subtypes:

  • Canker sores - usually HSV-1.
  • Genital herpes - usually HSV-2.

Histology/cytology

Features:[4]

  • Clear "ground glass" nuclei.
    • Rim of peripheral chromatin.
  • Nuclear inclusions.
  • Multinucleation with nuclear molding, i.e. multiple nuclei that touch over a large surface area.

Mnemonic - 3 Ms: Margination, Multinucleation, Molding.

Images

www:

  • HSV on a Pap test - showing multinucleation. (WC)

  • HSV esophagitis - very high mag. (WC)

  • HSV esophagitis - intermed. mag. (WC)

IHC

  • HSV-1 +ve (cytoplasmic and strong nuclear).
  • HSV-2 +ve.

Images:

Cytomegalovirus

  • Abbreviated CMV.
For pneumonia caused by CMV - see Cytomegalovirus pneumonia.
For colitis caused by CMV - see Cytomegalovirus colitis.

General

Microscopic

Features:

  • Very large nucleus (as the name implies) with clearing.
    • Classically described as owl's eye-like.
  • Granular cytoplasmic inclusions (red on H&E sections).

Notes:

  • Classically in endothelial cells.
    • In the context of esophageal ulcers, it is therefore useful to biopsy the base of the ulcer - if this is suspected.

Images

www:

IHC

  • IHC for CMV is available - highlights granular cytoplasmic inclusions; increases sensitivity.

Human papillomavirus

  • Abbreviated HPV.
Main article: Human papillomavirus

Adenovirus

General

Microscopic

Features:

  • "Smudge" cells[9] - black/blue blob ~ 10-15 micrometers. (???)

Notes:

  • May be morphologically similar to CMV, HSV, VZV inclusions.

Images:

Parvovirus

  • AKA Parvovirus B19.

General

Trivia:

  • First described in 1975.[12]
    • The "B19" part comes from the label for the specimen.[13]

Microscopic

Features:

  • Glassy (red) nuclear inclusions.[14]
  • Nuclear enlargement.

Images

  • Parvovirus - version 1 - very high mag. (WC)

  • Parvovirus - version 2 - very high mag. (WC)

www:

Epstein-Barr virus

Main article: Epstein-Barr virus

Polyomavirus

Main article: Polyomavirus

Human herpesvirus-8

Main article: Human herpesvirus-8

West Nile virus

  • Abbreviated WNV.

General

  • Uncommon pathologen.

Clinical:

  • Fever.
  • Muscle weakness.

Microscopic

Features:[17]

  • Perivascular clusters in grey and white matter:
    • Mononuclear infiltrates (lymphocytes, plasma cells).
    • Microglial nodules (macrophage clusters).

Measles virus

General

  • Causes Measles.
    • Should not be confused with Rubella (AKA German measles).
  • Uncommon due to widespread MMR vaccine.
    • However increasing in the last years most likely due to insufficient vaccination.
  • May develop weeks to years after infection.
  • Illness may be complicated by subacute sclerosing panencephalitis (SSPE) - a chronic neurodegenerative condition.[18]

Microscopic

Features:

  • +/-Intranuclear Cowdry type A inclusions.
    • Glassy (pink) nucleus.
  • Lymphocytes and macrophages (microglial cells).
    • May be mild in in measles inclusion body encephalitis.
  • Multinucleated cells.
  • Microglial nodules.
  • Demyelination.
  • Gliosis.

Notes:

  • Measles inclusions are intranuclear. RSV inclusions are intracytoplasmic.[citation needed]

Images

  • Measles pneumonia. (WC/CDC)

Rabies virus

General

  • Causes rabies.

Virus affects:[19]

  • Cerebral cortex.
  • Hippocamus pyramidal cells.
  • Purkinje cells.

Microscopic

Features:

  • Negri bodies:
    • Dense-appearing eosinophilic cytoplasmic bodies with a pale halo.

Images

  • Negri bodies. (WC/CDC)

  • Negri bodies - EM. (WC)

  • Negri bodies in cerebellar Purkinje cells. (WC/CDC).

www:

See also

References

  1. ↑ URL: http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675%2806%2970864-6&figureId=fig3&ecomponentId=mmc3. Accessed: 12 January 2010.
  2. ↑ URL: http://www.whonamedit.com/synd.cfm/3495.html. Accessed on: 22 January 2010.
  3. ↑ http://www.whonamedit.com/synd.cfm/3496.html. Accessed on: 22 January 2010.
  4. ↑ SM. 11 January 2010.
  5. ↑ URL: http://path.upmc.edu/cases/case120/dx.html. Accessed on: 28 February 2013.
  6. ↑ URL: http://www.antibodies-online.com/antibody/100405/anti-Herpes+Simplex+Virus+1+HSV1/. Accessed on: 28 February 2013.
  7. ↑ Tongsong, T.; Sukpan, K.; Wanapirak, C.; Phadungkiatwattna, P. (2008). "Fetal cytomegalovirus infection associated with cerebral hemorrhage, hydrops fetalis, and echogenic bowel: case report.". Fetal Diagn Ther 23 (3): 169-72. doi:10.1159/000116737. PMID 18417974.
  8. ↑ Aguerre, V.; Castaños, C.; Pena, HG.; Grenoville, M.; Murtagh, P. (Dec 2010). "Postinfectious bronchiolitis obliterans in children: clinical and pulmonary function findings.". Pediatr Pulmonol 45 (12): 1180-5. doi:10.1002/ppul.21304. PMID 20717912.
  9. ↑ URL: http://www.pathguy.com/lectures/infect.htm. Accessed on: 8 July 2010.
  10. ↑ URL:http://www.medscape.com/viewarticle/438534_2. Accessed on: 8 July 2010.
  11. ↑ Schwimmer, JA.; Markowitz, GS.; Valeri, A.; Appel, GB. (Mar 2003). "Collapsing glomerulopathy.". Semin Nephrol 23 (2): 209-18. doi:10.1053/snep.2003.50019. PMID 12704581.
  12. ↑ Cossart, YE.; Field, AM.; Cant, B.; Widdows, D. (Jan 1975). "Parvovirus-like particles in human sera.". Lancet 1 (7898): 72-3. PMID 46024.
  13. ↑ Servey JT, Reamy BV, Hodge J (February 2007). "Clinical presentations of parvovirus B19 infection". Am Fam Physician 75 (3): 373–6. PMID 17304869. http://www.aafp.org/afp/991001ap/1455.html.
  14. ↑ URL: http://www.pathguy.com/lectures/infect.htm. Accessed on: 8 July 2010.
  15. ↑ URL:http://info.fujita-hu.ac.jp/~tsutsumi/case/case210.htm. Accessed on: 8 February 2011.
  16. ↑ URL: http://www.scielo.br/scielo.php?pid=S0036-46652007000200007&script=sci_arttext. Accessed on: 18 August 2011.
  17. ↑ Sampson, BA.; Ambrosi, C.; Charlot, A.; Reiber, K.; Veress, JF.; Armbrustmacher, V. (May 2000). "The pathology of human West Nile Virus infection.". Hum Pathol 31 (5): 527-31. PMID 10836291.
  18. ↑ URL: http://path.upmc.edu/cases/case595/dx.html. Accessed on: 26 January 2012.
  19. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 424 Q36. ISBN 978-1416025887.
  20. ↑ Nuovo, GJ.; Defaria, DL.; Chanona-Vilchi, JG.; Zhang, Y. (Jan 2005). "Molecular detection of rabies encephalitis and correlation with cytokine expression.". Mod Pathol 18 (1): 62-7. doi:10.1038/modpathol.3800274. PMID 15389258. http://www.nature.com/modpathol/journal/v18/n1/full/3800274a.html.
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