Cytomegalovirus (CMV)

Infection: Characteristics
and Diagnosis
Cytomegalovirus (CMV) is a member of the Herpesviridae family, a group
of double-stranded DNA viruses known for their ability to establish
lifelong latent infections. This virus is characterized by its large genome,
enveloped virion, and preference for replicating in human fibroblasts.
Understanding the unique features and cytomorphological changes
associated with CMV infection is crucial for accurate diagnosis and
management.

DBL 21603 - CYTOLOGY AND CYTOPATHOLOGY

GROUP MEMBERS:

1. NURFITRAH BALQIS BINTI MOHD LIKI (068962)

2. NUR AIN AISYAH BINTI MOHD JAFRI (069938)

3. WONG PUI YAN (069503)

CASE 6:
Sarah, a 32-year-old woman is pregnant and has a history of systemic
lupus erythematosus (SLE), for which she takes immunosuppressive
medication. Sarah presents to her obstetrician for a routine prenatal
check-up. She denies any specific symptoms related to genital tract
infections. As part of routine prenatal care, Sarah's obstetrician decides
to perform a pap smear to assess the cervical cytology and screen for any
potential abnormalities or infections that could impact her pregnancy.
During the pap smear procedure, a sample of cells is collected from
Sarah's cervix using a spatula and cytobrush. The cytotechnologist may
incidentally observe characteristic cellular changes suggestive of viral
infection, prompting further investigation.
Features of cytomegalovirus (CMV)
Under Herpesviridae family

Double stranded DNA virus

Proteolytic virus

Enveloped virion
Presence of tegument or outer protein

Icosahedron shape capsid

diameter of whole capsid = 180 nm

Largest genome among herpes virus

replicates best in human fibroblasts

 Cytomorphological Hallmarks of
CMV Infection
1 Enlarged Cells 2 Nuclear Inclusions 3 Cytoplasmic
CMV-infected cells are The infected cells display
Inclusions
dramatically enlarged prominent, eosinophilic Numerous small
compared to uninfected intranuclear inclusions cytoplasmic inclusions
cells, a hallmark of the with a characteristic are also present in CMV-
infection. "owl's eye" appearance, infected cells.
surrounded by a clear
halo due to marginated
chromatin.
 Clinical Manifestations and
Transmission of CMV
Clinical Presentation
CMV infections are relatively
rare in the cervix and are
often asymptomatic.
However, they can cause fever
of unknown origin (FUO) in
some cases. The virus can be
transmitted through contact
with infected body fluids,
including placental, organ
transplant, blood transfusion,
breast milk, and sexual
contact.
Congenital CMV Lifelong Latency
Infection
Once acquired, CMV remains
Congenital CMV infection can latent in the body throughout
have serious consequences life and can reactivate when
for infants, including the immune system is
sensorineural hearing loss weakened, such as in HIV
and neurodevelopmental infection or during
delays. The transplacental immunosuppressive therapy.
transmission rate for primary
CMV infection in pregnant
women is around 32%, and
while most cases are
asymptomatic, some infants
may develop
thrombocytopenia, petechiae,
hepatomegaly, splenomegaly,
white matter changes with
seizures, and ophthalmologic
abnormalities.
Interpreting Cytological Findings
Bethesda System 2014
According to the Bethesda System 2014, the cytological findings consistent with CMV infection
should be reported as "Cellular changes consistent with cytomegalovirus".

Serological Testing
Serological tests, such as ELISA, can be used to detect the presence of anti-CMV antibodies (IgG
and IgM) in the patient's blood, providing additional information about the stage of infection.

Comprehensive Evaluation
A comprehensive evaluation, including clinical history, cytological findings, and appropriate
laboratory tests, is necessary to confirm the diagnosis of CMV infection and guide appropriate
management.

Importance of Accurate Diagnosis

Accurate diagnosis of CMV infection is crucial, as it can have significant implications for patient
care, particularly in immunocompromised individuals or during pregnancy.
 Additional tests to confirm
cytomegalovirus

Immunohistochemistry
(IHC)
detect cells affected by CMV
intranuclear inclusion in affected cell is
considered as hallmark feature
Histology
Stain with H & E staining
Hematoxylin-eosin–stained lung section
showing typical owl-eye inclusions (480X).

In-situ hybridization, direct or indirect

staining of intranuclear inclusion is done
by using CMV-specific antibodies linked to
indicator such as horseradish peroxidase

Polymerase chain reaction CMV Antigenemia

(PCR)
Polymerase chain reaction (PCR) can be used
to detect and quantify CMV DNA in blood and
tissue samples, providing a sensitive and
specific method for diagnosis.
The CMV antigenemia assay detects the
presence of the pp65 viral matrix protein in
leukocytes, indicating active CMV infection or
reactivation.
 Histological Features of CMV
Infection
1 2 3

Intranuclear Marginated Hematoxylin and

Inclusions
The hallmark histological
feature of CMV infection is
the presence of prominent,
eosinophilic intranuclear
inclusions within the affected
cells.
Chromatin
The intranuclear inclusions
are typically surrounded by a
clear halo due to the
margination of the
chromatin, creating the
characteristic "owl's eye"
appearance.
Eosin Staining
Histological examination
using hematoxylin and eosin
(H&E) staining can help
identify the distinctive
cytomorphological changes
associated with CMV
infection.
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ATTENTION !!!