Viruses

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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.

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.

General

  • Sexually transmitted.

Note:

  • Some tests can be done on formalin-fixed, paraffin-embedded tissue.[8]

Associated pathology

Oncocytic types

Known as "high risk" types; this grouping includes:[12]

  • HPV 18 - predominantly adenocarcinoma.[13]
    • Eighteen = adenocarcinoma.
  • HPV 16 - predominantly squamous cell carcinoma.[13]
    • Sixteen = squamous.
  • HPV 31.
  • HPV 33.
  • HPV 45.

Oncogenesis

Quick & dirty explanation of pathogenesis:[14][15]

  • 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:[16]

  • 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:

IHC

  • p16 +ve -- stains most cells infected by HPV.

Adenovirus

General

Microscopic

Features:

  • "Smudge" cells[18] - 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.[21]
    • The "B19" part comes from the label for the specimen.[22]

Microscopic

Features:

  • Glassy (red) nuclear inclusions.[23]
  • Nuclear enlargement.

Images

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

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

www:

Epstein-Barr virus

  • Abbreviated EBV

General

Note:

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

Associations

Cancer:[15]

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

Polyomavirus

Main article: Polyomavirus

Human herpesvirus-8

  • Commonly abbreviated HHV-8.

General

Associated with a number of cancers:

Other:

Microscopic

  • No light microscopic changes.

IHC

  • Usually HHV-8 +ve.

West Nile virus

  • Abbreviated WNV.

General

  • Uncommon pathologen.

Clinical:

  • Fever.
  • Muscle weakness.

Microscopic

Features:[34]

  • 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.
  • Illness may be complicated by subacute sclerosing panencephalitis (SSPE) - a chronic neurodegenerative condition.[35]

Microscopic

Features:

  • +/-Intranuclear Cowdry type A inclusions.
    • Glassy (pink) nucleus.
  • Lymphocytes and macrophages (microglial cells).
  • Demyelination.

Notes:

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

Images

  • Measles pneumonia. (WC/CDC)

Rabies virus

General

  • Causes rabies.

Virus affects:[36]

  • 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. ↑ Black, CC.; Bentley, HA.; Davis, TH.; Tsongalis, GJ. (Dec 2010). "Use of a linear array for the detection of human papillomavirus genotypes in head and neck cancer.". Arch Pathol Lab Med 134 (12): 1813-7. doi:10.1043/2009-0592-OAR.1. PMID 21128780.
  9. ↑ 9.0 9.1 9.2 9.3 Borget, I.; Abramowitz, L.; Mathevet, P. (Jul 2011). "Economic burden of HPV-related cancers in France.". Vaccine 29 (32): 5245-9. doi:10.1016/j.vaccine.2011.05.018. PMID 21616117.
  10. ↑ Zhang, QY.; Zhang, DH.; Shen, ZY.; Xu, LY.; Li, EM.; Au, WW. (Mar 2011). "Infection and integration of human papillomavirus in esophageal carcinoma.". Int J Hyg Environ Health 214 (2): 156-61. doi:10.1016/j.ijheh.2010.11.001. PMID 21130683.
  11. ↑ Iyer, A.; Rajendran, V.; Adamson, CS.; Peng, Z.; Cooper, K.; Evans, MF. (Mar 2011). "Human papillomavirus is detectable in Barrett's esophagus and esophageal carcinoma but is unlikely to be of any etiologic significance.". J Clin Virol 50 (3): 205-8. doi:10.1016/j.jcv.2010.11.015. PMID 21169053.
  12. ↑ Ntova, CK.; Kottaridi, C.; Chranioti, A.; Spathis, A.; Kassanos, D.; Paraskevaidis, E.; Karakitsos, P. (2012). "Genetic Variability and Phylogeny of High Risk HPV Type 16, 18, 31, 33 and 45 L1 Gene in Greek Women.". Int J Mol Sci 13 (1): 1-17. doi:10.3390/ijms13010001. PMID 22312235.
  13. ↑ 13.0 13.1 De Boer, MA.; Peters, LA.; Aziz, MF.; Siregar, B.; Cornain, S.; Vrede, MA.; Jordanova, ES.; Fleuren, GJ. (Apr 2005). "Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries.". Int J Cancer 114 (3): 422-5. doi:10.1002/ijc.20727. PMID 15551313.
  14. ↑ Münger, K.; Howley, PM. (Nov 2002). "Human papillomavirus immortalization and transformation functions.". Virus Res 89 (2): 213-28. PMID 12445661.
  15. ↑ 15.0 15.1 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.
  16. ↑ McCormack, PL.; Joura, EA. (Oct 2011). "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†.". BioDrugs 25 (5): 339-43. doi:10.2165/11205060-000000000-00000. PMID 21942919.
  17. ↑ 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.
  18. ↑ URL: http://www.pathguy.com/lectures/infect.htm. Accessed on: 8 July 2010.
  19. ↑ URL:http://www.medscape.com/viewarticle/438534_2. Accessed on: 8 July 2010.
  20. ↑ 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.
  21. ↑ Cossart, YE.; Field, AM.; Cant, B.; Widdows, D. (Jan 1975). "Parvovirus-like particles in human sera.". Lancet 1 (7898): 72-3. PMID 46024.
  22. ↑ 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.
  23. ↑ URL: http://www.pathguy.com/lectures/infect.htm. Accessed on: 8 July 2010.
  24. ↑ URL:http://info.fujita-hu.ac.jp/~tsutsumi/case/case210.htm. Accessed on: 8 February 2011.
  25. ↑ URL: http://www.scielo.br/scielo.php?pid=S0036-46652007000200007&script=sci_arttext. Accessed on: 18 August 2011.
  26. ↑ URL: http://www.meddean.luc.edu/lumen/MedEd/orfpath/herpes.htm. Accessed on: 14 April 2011.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ "Role of EBERs in the pathogenesis of EBV infection". Adv. Cancer Res. 107: 119–36. 2010. doi:10.1016/S0065-230X(10)07004-1. PMID 20399962.
  34. ↑ 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.
  35. ↑ URL: http://path.upmc.edu/cases/case595/dx.html. Accessed on: 26 January 2012.
  36. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 424 Q36. ISBN 978-1416025887.
  37. ↑ 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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