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Herpes simplex virus (HSV)

Reviewer: Farnaz Hasteh, M.D., UCSD Medical Center (see Reviewers page)
Revised: 24 September 2012, last major update November 2010
Copyright: (c) 2006-2012, PathologyOutlines.com, Inc.


● Common disease caused by herpes simplex 1 (HSV1) or herpes virus simplex 2 (HSV2)


● HSV1 antibodies increase with age starting in childhood and correlate with socioeconomic status, race and cultural group; by age 30 years, 50% of individuals of high socioeconomic status and 80% of lower socioeconomic status are seropositive
● HSV2 antibodies correlate with sexual activity, with a lifetime seroprevalence of 20%-80% of population (eMedicine)


● HSV2 was traditionally associated with genital tract infections, but a recent study of college students shows 60% of genital herpes cases due to HSV1 (J Am Coll Health 2009;57:389)

Clinical features

● Either asymptomatic or painful blisters initially; less severe symptoms in subsequent episodes
● Cytology, in-situ hybridization and PCR helpful for rapid diagnosis (Diagn Cytopathol 2003;29:246)
● Liquid based pap tests may be more sensitive (Diagn Cytopathol 2008;36:94)
● Virus can be dormant for long periods
● Dangerous in pregnant women (may cause encephalitis in infants)


● Antiviral medication decreases the duration of disease and prevents outbreaks; goal of pharmacotherapy is to reduce morbidity and prevent complications (eMedicine)

Cytology description

● Early changes can include mononucleated cells (DeMay: The Pap Test: Exfoliative Gynecologic Cytology; 2005)
● Multinucleated cells with dense, intranuclear Cowdry-type viral inclusions
● Nuclei have ground glass appearance due to accumulation of viral particles, which causes peripheral margination of chromatin
● Also nuclear molding
“Three M’s of herpes” - margination of nuclei, molding and multinucleation
Cowdry: intranuclear eosinophilic amorphous or droplet-like bodies surrounded by a clear halo, with (type A, herpes) or without (type B, adenovirus or poliovirus) margination of chromatin on the nuclear membrane
● Cowdry type A are highly characteristic but they are only seen in less than half of cases (Acta Cytol 1994;38:43)

Cytology images

Various images (note: descriptions of images are correct, but heading of "invasive squamous cell carcinoma" on large images is incorrect)


Various images

Differential diagnosis

● Inflammatory cells with multiple nuclei (lack discrete nuclear molding)

End of Cervix-cytology > Inflammation/parasites > Herpes simplex virus (HSV)

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