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:

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

www:

Epstein-Barr virus

  • Abbreviated EBV

General

Note:

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

Associations

Cancer:[15]

Other:

Microscopic

Features:

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

Images:

IHC

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

Molecular

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:[33]

  • 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.[34]

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

Rabies virus

General

  • Causes rabies.

Virus affects:[35]

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

Microscopic

Features:

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

Images

www:

See also

References

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