Case Report
Herpes Simplex Viral Cytopathic Effect in Anorectal Cytology of a HIV Positive Homosexual Man Presented with Acute Proctitis
Gazal Alsaati1 and Zahra Maleki2*
1Department of Pathology, Georgetown University, USA
2Department of Cytopathology, The Johns Hopkins Hospital, USA
*Corresponding author: Zahra Maleki, Department of Cytopathology, The Johns Hopkins Hospital, 600 N. Wolfe Street/Carnegie 412C, Baltimore, MD 21287, USA
Published: 16 Mar, 2017
Cite this article as: Alsaati G, Maleki Z. Herpes Simplex
Viral Cytopathic Effect in Anorectal
Cytology of a HIV Positive Homosexual
Man Presented with Acute Proctitis. Ann
Clin Case Rep. 2017; 2: 1304.
Abstract
Objective: Herpes Simplex Virus (HSV) cytopathic effects in anorectal cytology specimens have
rarely been described. Presence of HSV viral cytopathic effect in anorectal pap cytology can confirm
the diagnosis in symptomatic patients. Awareness of herpetic proctitis in HIV positive and/
or homosexual men may initiate prompt diagnosis and treatment. An anorectal cytology is cost
effective, and provides a time efficient diagnosis.
Design: We encountered an anorectal pap smear of a young homosexual man who was newly
diagnosed with HIV and presented with symptomatic acute analproctitis.
Results: The anorectal pap smear cytology demonstrated the classic cytopathic effect of herpessimplex
in infected squamous cells and columnar cells of the anal canal. This was also confirmed
with positive viral culture of the anal canal for HSV-2.
Conclusion: In symptomatic patients the identification of HSV viral cytopathic effect on anorectal
cytology will confirm the diagnosis of herpeticproctitis. Although not commonly seen, the anorectal
cytology in this case demonstrates the classic cytopathic effects of herpes-simplex infection.
Keywords: HIV/AIDS; Anorectal region; Antiviral therapy; Immunodeficiency; Mucosal infection
Introduction
The characteristic viral cytopathic effects of herpes simplex virus (HSV) in anorectal cytology
specimens are rarely encountered. When present, if clinically asymptomatic, this could represent
subclinical shedding of the HSV. Men who have sex with men (MSM) have especially higher rates
of shedding HSV than the general population [1,2]. HSV-2-seropositive MSM has more frequent
subclinical HSV-2 shedding predominantly from the perianal area and more frequent prodromal
HSV-2 shedding [1]. The frequency of viral shedding is comparable in men and women [2]. In
symptomatic patients the identification of HSV viral cytopathic effect on anorectal cytology will
confirm the diagnosis of herpes proctitis.
HSV- 2 is one of the most common sexually transmitted Infections (STIs) in the United States
particularly among young people ages 15-24. In February of 2013, the Center of Disease Control
(CDC) estimated that there are approximately 20 million new cases of STIs diagnosed every year
of which 766,000 are caused by HSV-2 [3]. It is worth noting that the routine screening for HSV-
2 infection is not recommended for the general population. However the CDC does recommend
routine screening for herpeticproctitis in high risk populations for instance MSM and in individuals
who are positive for the human immunodeficiency virus (HIV) as the HIV can be transmitted
through the herpetic vesicles [3]. In immunocompetent individuals HSV can be transmitted
through herpetic vesicles. The viral cytopathic effect can appear as early as four hours after infection
with herpes virus [4]. Reissing and Melnick [5] studied the herpes virus and its effect on the cells
in vitro thoroughly early in the 1950’s using electron microscopy. They described the changes
occurring in infected cells and noted that the earliest sign within four hours of incubation was
coarsening of the nuclear chromatin and margination of the chromatin toward the periphery of the
infected nucleus leaving a central halo. In the late stage 24 to 36 hours there is a marked decrease
or near absence of chromatin material giving rise to a membrane-bound clear glassy vesicle which is now known as the viral inclusion body [5]. It is hypothesized
that the virus disseminates the host nuclear structures and intranuclear
framework thereby remodeling the infected cell nucleus and
providing a structural basis for efficient viral DNA replication and
ultimately enhancing the replication process [6,7]. In 1974 Enlander
et al. [8] further characterized the nuclear features of molding
and multinucleation by the decrease in number of micro-villi in
between infected cells as well as diminished intracellular filaments.
Adjacent infected cells are thought to merge forming a larger
multinucleated cell [9]. Reviewing the literature the authors did not
find any reports describing the histopathologic differences between
asymptomatic viral shedding vs. symptomatic disease. According to
CDC all patients with acute proctitis should be evaluated for HSV N.
gonorrhoeae, Clamydiatrachomatis and T.pallidum. Interestingly
the 2015 sexually transmitted disease treatment guidelines by
CDC do not recognize cytology as a sensitive and specific means
to detect HSV infection of genital lesions [10]. As discussed above
the cytomorphologic features of epithelial cells infected with HSV
are well established and HSV infection is routinely diagnosed on
cytology material by cytopathologists. We have reported HSV viral
cytopathatic effects in urine cytology previousely [11]. Herein we
report HSV viral cytopathic effects in anal cytology.
Case Presentation
A 20-year-old homosexual male who was diagnosed with HIV six
months prior to his current symptoms presented to the emergency
department complaining of severe rectal pain and a sore throat that
developed 3 days after having repetitive unprotected anal and oral
intercourse with a new male partner. He also described a white
creamy foul smelling rectal discharge as well as difficulty speaking
and dysphagia. On examination scant white mucoid discharge
was present around the anus but no anal or penile lesions were
identified. His oropharynx showed unilateral tonsillar erythema and
exudate with a tender enlarged cervical lymph node. The differential
diagnosis at the time was gonorrhea/chlamydia (GC/CT) infection lymphogranulomavenereum (LGV) HSV proctitis and anal trauma
with foreign material. Anal trauma was excluded based on history and
physical examination. A rectal culture was obtained and confirmed
HSV-2 rectal proctitis. Rectal and urine cultures were negative for GC/
CT. Cytological evaluation of the anorectal specimen was expedited.
A cytospin slide was prepared and stained with Papanicolaou stain.
It revealed scattered squamous cells and columnar cells exhibiting
large ground-glass nuclei with chromatin marginating towards the
membrane (Figure 1 and 2). Mono and multinucleated cells contained
nuclei with ground glass appearance and margination of chromatin
on the nuclear membrane. These changes are due to accumulation of
viral particles in the center of the nuclei which causes margination of
chromatin to the periphery. In addition multinucleated cells displayed
nuclear molding. Multinucleation margination of chromatin and
molding which are known as “ three M’s of herpes” were present in
our examined anal cytology material.
These changes were classic for viral cytopathic effect consistent
with Herpes virus. Additional findings were rare atypical squamous
cells of undetermined significance (ASC-US) and scattered acute
inflammatory cells in the background.
Figure 1
Figure 1
A cell infected with HSV displaying mulinucleation; chromatin
margination and nuclear molding Papanicolaou Stain x400).
Figure 2
Figure 2
HSV viral cytopathic effect including a ground glass chromatin;
multinuceation; chromatinmargination and nuclear molding in a columnar cell
(Papanicolaou Stain x400).
Conclusion
Herpeticproctitis is common in MSM with a typical acute presentation. Although not commonly seen the anorectal cytology in this case demonstrates the classic cytopathic effects of herpes-simplex in infected squamous cells and columnar cells of the anal canal.
Author Contributions
Zahra Maleki has contributed in design and acquisition of clinical data for the case report and providing the images and GazalAlsaati has contributed in writing the case and literature research. Both authors have worked equally.
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