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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
EPSTEIN-BARR VIRUS (HHV-4) INFECTION
Large, atypical lymphoid cells are shown within a diffuse
large B-cell lymphoma, which was positive for EBV by in
situ hybridization. Transformation by EBV leads to a large
number of malignant lesions.
Viral Infections: Morphological Diagnosis of Viral Infections
TERMINOLOGY
Abbreviations
Epstein-Barr virus (EBV)
Synonyms
Infectious mononucleosis
Human herpesvirus-4 (HHV-4)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Ubiquitous virus
Infects B-lineage lymphocytes
CD21 (complement receptor 2) bound by viral
gp350 and MHC class II bound by gp42
Fusion and entry into cell
Infects epithelial cells
-1 integrins bound by viral BMRF-2 and V--6/-8 integrins bound by viral gH/gL
Fusion and entry into cell
Initial infection (asymptomatic in most patients)
Infectious mononucleosis: Flu-like systemic
disease
Chronic infection
Latency: Asymptomatic
Reactivation: Flu-like systemic disease
Transformation: Malignancies
CLINICAL ISSUES
Site
Infectious mononucleosis &/or reactivation
Lymph nodes, liver, skin
Transformation = malignancies
I
B-lineage malignancies of any body sites
Nasopharyngeal carcinoma
Large atypical lymphocytes are shown in a peripheral
blood smear from a patient with acute EBV infection. The
dark open chromatin and nuclear morphology confirm
the lymphocyte identity.
Presentation
Infectious mononucleosis
Fatigue
Lymphadenopathy
Acute pharyngitis
Hepatosplenomegaly jaundice (adults)
Frank hepatitis (rare)
Rash (less common)
Maculopapular
Palatal petechiae
Erythema nodosum/multiforme (very rare)
Periorbital edema (rare)
Incubation period: 4-6 weeks
Viral prodrome: 1-2 weeks
Laboratory Tests
Lymphocyte + monocyte count > 50%
Heterophil agglutination antibody test positive
EBV viral capsid antigen IgM positive
Transaminitis (with liver involvement)
Natural History
Rare complications of primary infection (< 5%)
Guillain-Barr syndrome
Fulminant hepatitis
Splenic rupture
Hemophagocytic lymphohistiocytosis
Treatment
Supportive (complication management is specific to
symptom &/or manifestation)
Prognosis
95% of primary infections resolve without
complications
Lifelong viral infection with latency
Risk of EBV-related malignancies
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EPSTEIN-BARR VIRUS (HHV-4) INFECTION
Viral Infections: Morphological Diagnosis of Viral Infections
Etiology
Infects B-lineage lymphocytes
Infectious mononucleosis: Flu-like systemic disease
Clinical Issues
50% of children at 5 years of age are seropositive
95% of adults are seropositive
Infectious mononucleosis &/or reactivation
Lymphadenopathy
Hepatosplenomegaly jaundice
MICROBIOLOGY
Virus Features
Enveloped, lytic/latent, double-stranded DNA virus
120-180 nm
192,000 bp genome (85 genes)
MACROSCOPIC FEATURES
Lymphadenopathy
Large reactive lymph nodes may be biopsied in
nonclassical cases
Primary EBV in children may histologically mimic
lymphoma
Key Facts
Lymphocyte + monocyte count > 50%
EBV VCA IgM positive
Microscopic Pathology
Reactive lymph nodes with prominent germinal
centers
Large, reactive lymphocytes with abundant
cytoplasm
ANCILLARY TESTS
In Situ Hybridization
Direct probe for EBV nuclear antigen (EBNA)
Serologic Testing
IgM for VCA is present in acute, recurrent, or
reactivated disease
IgG for VCA peaks 2-4 months after acute infection
(persists for life of patient)
IgG for EBNA or early antigen (EA) peaks 2-8 months
after acute infection
Immunosuppressed patients may respond abnormally
and present incomplete patterns
Rash (less common)
Positive IgM for VCA in presence of any other
pattern of antibodies suggests active disease
MICROSCOPIC PATHOLOGY
Histologic Features
Reactive lymph nodes with prominent germinal
centers
Hepatitis with increased lymphoid cells, nonaggregate,
in sinusoids
Cytologic Features
Large, reactive lymphocytes with abundant cytoplasm
Commonly seen in peripheral blood during acute
infection
IMAGE GALLERY
DIFFERENTIAL DIAGNOSIS
Cytomegalovirus Primary Infection
May present with mono-like syndrome identical to
EBV
Primary HIV Infection
May present with mono-like syndrome identical to
EBV
SELECTED REFERENCES
1. Usmani GN et al: Advances in understanding the
pathogenesis of HLH. Br J Haematol. 161(5):609-22, 2013
(Left) A peripheral blood smear demonstrates acute EBV infection with 3 large reactive lymphocytes ; a normal lymphocyte for comparison
is shown
hybridization for EBER
. (Center) EBV hepatitis shows linear filing of lymphocytes within the sinusoids. (Right) EBV hepatitis is shown with in situ
.
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HEPATITIS B AND D VIRUS INFECTIONS
Ground-glass hepatocytes have glassy eosinophilic
cytoplasm representing proliferation of smooth ER in
response to hepatitis B surface antigen (HBsAg).
Viral Infections: Morphological Diagnosis of Viral Infections
TERMINOLOGY
Abbreviations
Hepatitis B virus (HBV)
Hepatitis D virus (HDV)
Synonyms
Blood-borne hepatitis
Definitions
Hepadnaviridae family
"Hepa" derived from "of the liver"
"DNA" for DNA viruses in this family
Australia antigen: Hepatitis B surface antigen (HBsAg)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Transmitted parenterally
Vertical transmission: Mothers to newborn infants
Horizontal transmission: Between young children
Sexual contact
Liver injury appears to be immune mediated
HBV-specific T cells play key role in pathogenesis
and viral clearance
Carcinogenesis
Increased risk of hepatocellular carcinoma (HCC)
HCC strongly associated with presence of cirrhosis
HCC occurs in absence of cirrhosis, strongly
associated with high HBV viral loads
CLINICAL ISSUES
Epidemiology
Incidence
I
400 million people worldwide are chronically
infected with HBV
Africa and Asia have carrier rates of as high as 15%
1
Hepatitis B-infected hepatocytes have pale pink, finely
granular intranuclear inclusions (sanded nuclei )
representing nuclear accumulation of HBcAg.
North America has carrier rate of ~ 5%
HDV infection occurs as coinfection or
superinfection of HBV infection
Site
Liver
Presentation
Acute hepatitis B
> 50% are asymptomatic
Symptoms include mild flu-like syndrome, nausea,
vomiting, jaundice
< 1% develop fulminant liver failure leading to
death or liver transplantation
Serum HBsAg and anti-HBc virus IgM Ab positive
Chronic hepatitis B
Serum HBsAg positive and anti-HBc virus IgM Ab
negative
Hepatitis D coinfection or superinfection
Increase chance of liver failure in acute hepatitis B
More rapid progression to cirrhosis in chronic
hepatitis B
Laboratory Tests
Serology for HBV viral antigens
Hepatitis B surface antigen (HBsAg)
Present in natural infection and vaccinated
patients (4-24 weeks after infection)
Hepatitis B core antigen (HBcAg)
Only present in infected patients
Not detected in routine clinical testing
Hepatitis B early antigen (HBeAg)
Only present in infected patients (5-14 weeks after
infection)
Serology for anti-HBV antibodies
Anti-HBs
Present in natural infection late (32 weeks after
infection)
Present in vaccinated patients (1-2 months after
vaccination)
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HEPATITIS B AND D VIRUS INFECTIONS
Etiology
Sexual contact
Vertical transmission: Mothers to newborn infants
Horizontal transmission: Between young children
Clinical Issues
10% of infected individuals become chronically
infected
Lifelong risk of developing cirrhosis &/or HCC in
chronic hepatitis B
Albumin
Low in chronic infection implies cirrhosis
Bilirubin
High in chronic phase implies cirrhosis
Prothrombin time (PT)
Prolonged in chronic disease implies cirrhosis
Key Facts
Macroscopic Pathology
Cirrhosis: Nodularity (macronodular or mixed macroand micronodular) and scarring
Microscopic Pathology
Acute hepatitis B
Chronic hepatitis B
Grading denotes inflammatory activity whereas
staging indicates degree of fibrosis
Viral Infections: Morphological Diagnosis of Viral Infections
Hepatocytic swelling, mononuclear cell infiltrates,
spotty necrosis, apoptotic bodies, confluent and
bridging necrosis, collapse of hepatocytic cords,
hepatocytic regeneration
Portal inflammation, interface hepatitis, lobular
hepatitis, fibrosis
Anti-HBc
IgM present 6-32 weeks after infection
Disappears as Anti-HBs appear
Not present in vaccinated patients
Anti-HBe
Present 14 weeks after infection and persists
indefinitely in naturally infected patients
Not present in vaccinated patients
Serum HBV DNA and viral load
Utilized to monitor response to therapy
Liver function and transaminase levels
Albumin
Variable in acute infection
Low in chronic infection implies cirrhosis
Bilirubin
High in acute infection
Stabilizes during chronic phase
High in chronic phase implies cirrhosis
Prothrombin time (PT)
Prolonged in chronic disease implies cirrhosis
Alanine transaminase (ALT)
High in acute infection
Stabilizes (borderline high) during chronic phase
Aspartate transaminase (AST)
High in acute infection
Stabilizes (borderline high) during chronic phase
Natural History
10% of infected individuals become chronically
infected
Lifelong risk of developing cirrhosis &/or HCC in
chronic hepatitis B
Cirrhosis is not prerequisite for developing HCC
HBV viral genome can act as oncoprotein and
intergrade into host genome
Coinfection with HIV and HCV is common, as they
share common transmission route
Treatment
Drugs
Nucleoside analogue therapy: Lamivudine, adefovir,
entecavir
Interferon
Prognosis
Viral clearance dependent on age when infected
Complete recovery in 95% of adults
Complete recovery in only 5% of infants
Estimated lifetime risk of complications = 40%
Cirrhosis &/or hepatocellular carcinoma
MICROBIOLOGY
Virus Features
Hepatitis B
Partially double-stranded DNA virus
42 nm
3,200 bp genome
Hepatitis D
Incomplete, small, circular, enveloped RNA virus
Can only propagate in presence of HBV
36 nm
1,700 bp genome
Culture
Not a relevant diagnostic for hepatitis B or D diagnosis
MACROSCOPIC FEATURES
Cirrhosis
Nodularity (macronodular or mixed macro- and
micronodular) and scarring
MICROSCOPIC PATHOLOGY
Histologic Features
Acute hepatitis B
Hepatocytic swelling
Mononuclear inflammatory cell infiltrates
Lymphocytes
Plasma cells
Apoptosis abundant with spotty necrosis
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A
Confluent or bridging necrosis
Hepatocytic cord collapse
Best seen on reticulin stain
Regenerative changes in hepatocytes
Chronic hepatitis B
Portal inflammation
Expand portal tracts
Lymphocytes with Kupffer cells and plasma cells
Interface hepatitis
Apoptosis and inflammation beyond limiting
plate
Lobular hepatitis
Fibrosis
Early: Portal regions
Mid: Beyond limiting plate
Late: Bridging (between portal and central regions)
Fibrosis staging in biopsy has clinical treatment
implications
Ground-glass hepatocytes
Sanded nuclei of hepatocytes
Viral Infections: Morphological Diagnosis of Viral Infections
Cytologic Features
Balloon cell degeneration
Pleomorphic hepatocytes, increased mitosis,
binucleate forms
Isolated hepatocyte necrosis
Mononuclear (lymphocyte) infiltrates
Kupffer cell hyperplasia
ANCILLARY TESTS
Immunohistochemistry
Directed at HBV surface and core antigens
DIFFERENTIAL DIAGNOSIS
Hepatitis A (HAV)
Serological discrimination
HBV vs. HAV
Food or travel associated
utoimmune Hepatitis
Serological discrimination
Antinuclear antibodies (ANA)
Anti-smooth muscle antibodies (SMA)
Anti-liver kidney microsome type 1 antibodies
(LKM-1)
Plasma cells
Chronic Hepatitis C
Serological discrimination
HBV vs. HCV
Portal lymphoid aggregates &/or steatosis
Drug-Associated Hepatitis
Clinical history of recent drug changes
Eosinophils
HEPATITIS B AND D VIRUS INFECTIONS
Other Infectious Hepatitides
CMV hepatitis
EBV hepatitis
Herpes simplex virus hepatitis
Yellow fever
Dengue fever
Syphilitic hepatitis
Primary Biliary Cirrhosis
Florid duct lesion (granuloma) destroying interlobular
bile duct is diagnostic
Other Causes of Ground-Glass Cells
Lafora disease
Cyanamide toxicity
Fibrinogen storage disease
Glycogen pseudo-ground-glass cell change
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Liver biopsy should
Grade and stage HBV disease
Exclude other liver diseases
Coinfections in HBV are common due to transmission
overlap
HCV
HIV
HDV
Appropriate serological work-up must include these
viruses
Unlike hepatitis C, recurrent hepatitis B after liver
transplantation is rare due to advent of antiviral
prophylaxis
In posttransplant biopsies, be cautious in diagnosing
recurrent HBV infection
SELECTED REFERENCES
1. Brechot C et al: Hepatitis B virus (HBV)-related
hepatocellular carcinoma (HCC): molecular mechanisms
and novel paradigms. Pathol Biol (Paris). 58(4):278-87,
2010
2. Liang TJ: Hepatitis B: the virus and disease. Hepatology.
49(5 Suppl):S13-21, 2009
3. Mani H et al: Liver biopsy findings in chronic hepatitis B.
Hepatology. 49(5 Suppl):S61-71, 2009
4. McMahon BJ: The natural history of chronic hepatitis B
virus infection. Hepatology. 49(5 Suppl):S45-55, 2009
5. Goodman ZD: Grading and staging systems for
inflammation and fibrosis in chronic liver diseases. J
Hepatol. 47(4):598-607, 2007
6. Batts KP et al: Chronic hepatitis. An update on
terminology and reporting. Am J Surg Pathol.
19(12):1409-17, 1995
7. Ishak KG: Light microscopic morphology of viral hepatitis.
Am J Clin Pathol. 65(5 Suppl):787-827, 1976
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Hepatitis E
Food or travel associated
HEPATITIS B AND D VIRUS INFECTIONS
p
Gross, Microscopic, and Ancillary Features
Viral Infections: Morphological Diagnosis of Viral Infections
(Left) A gross photograph
of a liver at autopsy
demonstrates end-stage
cirrhosis with a distinctive
nodular liver surface. (Right)
Hematoxylin & eosin section
illustrates chronic hepatitis
B with portal inflammatory
infiltrates and apoptotic
bodies in the lobule.
(Left) Hematoxylin & eosin
section shows interface
hepatitis in chronic hepatitis
B consisting of chronic
inflammatory cells that
extend beyond the limiting
late and replace dead
hepatocytes. (Right) Masson
trichrome stain shows
collagen strands that extend
beyond portal tracts to reach
the central region and form
bridging septa in chronic
hepatitis B.
(Left) Immunohistochemical
stain for anti-HBc
(core antigen) shows
both cytoplasmic and
nuclear staining. (Right)
Immunohistochemical
stain for anti-HBs (surface
antigen) shows cytoplasmic
staining.
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HERPES SIMPLEX VIRUS 1 AND 2 (HSV-1, HSV-2) INFECTIONS
A multinucleated herpesvirus infected cell is shown at
the base of an inflammatory collection in the epithelium
of a perineal skin lesion.
Viral Infections: Morphological Diagnosis of Viral Infections
TERMINOLOGY
Abbreviations
Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)
Synonyms
Genital herpes
Cold sore or fever blister
Herpetic whitlow
Herpes gladiatorum
Ocular herpes
Neonatal herpes
Herpes encephalitis
Mollaret meningitis
Definitions
Greek: "Herpein" (to creep)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Herpesviridae: Ubiquitous enveloped icosahedral
double-stranded DNA viruses present in most
vertebrates
Herpes simplex virus 1 and 2
Common human virus transmitted by contact
HSV-1 and HSV-2 can cause oral/genital lesions
HSV-1 = oral
HSV-2 = genital
Infects mucoepithelial cells
Heparan sulfate bound by viral gB (glycoprotein)
Fusion and entry into cell
Lytic infection
Initial infection
Erythematous-based vesicles filled with viral
I
particles
Progress to
Pustules
1
Immunohistochemistry for herpes simplex 1/2 viral
antigens is shown in squamous epithelium adjacent to
a vesicle. Viral protein present in cells without viral
cytopathic effect can be appreciated.
Crusted lesions
Ulcerations
Fulminant primary infection
HSV encephalitis
HSV hepatitis
Chronic infection
Latency
Permanent infection
No vaccine or cure
Resides in neurons
Reactivation
Immunocompetent: Resurgence in primary sites
Immunosuppressed: Dissemination to any body
site
CLINICAL ISSUES
Epidemiology
Common human virus affecting any age group
Direct human contact for transmission
Oral/genital most common
Incidence increases with age/number of oral
contacts and sex partners
Geographic variability of incidence
Lowest: Japan, Western Europe (30,000 to
300,000/year)
Middle: North America, Eastern Europe (600,000
to 800,000/year)
Highest: Sub-Saharan Africa, Eastern Asia (3 to 3.5
million/year)
Site
Primary HSV infection (most common)
Oral skin/mucosa (HSV-1)
Nongenital skin (HSV-1 or -2)
Genital skin (HSV-2)
Temporal lobes, uni- or bilateral (HSV-1)
Eye
Liver (fulminant hepatitis)
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HERPES SIMPLEX VIRUS 1 AND 2 (HSV-1, HSV-2) INFECTIONS
Clinical Issues
Primary HSV infection (most common)
Oral skin/mucosa (HSV-1)
Genital skin (HSV-2)
Temporal lobes, uni- or bilateral (HSV-1)
Liver (fulminant hepatitis)
Immunocompromised
Mild to severe (life threatening)
HSV IgM positive (primary infection)
HSV PCR
Qualitative (primary diagnosis on CSF)
Microscopic Pathology
Epithelial vesicles with viral cytopathic effect
Pustules with neutrophils
Necrosis with little inflammation (fulminant disease)
Multinucleation, classic Cowdry A appearance
Reactivation
Immunocompetent
Oral skin/mucosa (HSV-1)
Genital skin (HSV-2)
Immunocompromised
Any body site or organ
Mild to severe (life threatening)
Presentation
Primary HSV infection
Painful new lesions of mouth/genitalia
Severe headache with temporal lobe signs
New onset rash with historical contact
Newborn ocular lesions (infected mother)
New onset right upper quadrant pain jaundice
Reactivation
Resurgence of painful lesions on mouth/genitalia
New onset of disseminated rash
(immunosuppressed)
Organ site-specific symptoms (any site)
Example A: Painful swallowing = esophageal HSV
Example B: Painful large oral ulcer = HSV with
secondary colonization
Laboratory Tests
HSV IgM positive (primary infection)
HSV IgG positive (ongoing, latent, reactivation)
HSV PCR
Qualitative (primary diagnosis on CSF)
Quantitative (following immunosuppression)
Natural History
Primary infection
Self-limited (resolution) to life-threatening (CNS/
liver involvement)
Lifelong latency
Latency/reactivation cycles (with outbreaks)
Plethora of potential triggers
Traumatic injury
Surgery
Exposure to extreme elements
Menstruation
Key Facts
Top Differential Diagnoses
Herpesvirus family
Adenovirus
Other viral infections (all sites)
Bacterial infections (all sites)
Diagnostic Checklist
New onset vesicular rash in an immunosuppressed or
pregnant female
Exaggerated or nonhealing oral ulcer with
superinfection
Histologic diagnoses based on viral cytopathic change
should be confirmed by immunohistochemistry
Treatment
Primary treatment &/or suppression
Alternatives in cases of resistance
Prognosis
Lifelong infection with common reactivation within
1st year of infection
Fulminant disease (encephalitis &/or hepatitis) is
rapidly fatal without treatment
Immunosuppression leads to more severe disease with
reactivation
MICROBIOLOGY
Virus Features
Double-stranded DNA virus
Icosopentahedral capsid composed of 162 capsomers
4 envelope proteins (gD, gH, gL, and gB) are essential
for entry to host cells
Culture
High-quality swab or needle aspiration placed in viral
transport media required
Virus is propagated on 1 of a variety of susceptible
mammalian cell lines
Coinfection
HIV infection
Viral protein VP16 (trans-acting protein) induces
immediate gene transcription in host transcription
factors
Acyclovir
Valacyclovir
Famciclovir
Penciclovir
HSV-1 has a genome of 152 kilobases encoding > 80
proteins
HSV-2 has a genome of 155 kilobases encoding > 70
proteins
Grows in ~ 1 week
Will grow on all mammalian cells, including those
used for Adenovirus, VZV, and CMV culture
Viral Infections: Morphological Diagnosis of Viral Infections
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HERPES SIMPLEX VIRUS 1 AND 2 (HSV-1, HSV-2) INFECTIONS
Often overgrows these viruses (they take > 1 week)
Difficult to exclude coinfection if suspected
(although rare)
Virus is subtyped after culture by HSV-1- or HSV-2specific antibodies
Molecular techniques have largely replaced culture
methods
MACROSCOPIC FEATURES
Skin
Vesicles/pustules with erythematous base
Oral Mucosa/Esophagus
Linear to irregular ulcers with purulent crust
DIFFERENTIAL DIAGNOSIS
Herpesvirus Family
Cytomegalovirus
"Owl’s-eye" nucleus
Nuclear clearing and a large pink-purple
intranuclear inclusion
Varicella-zoster virus
Classic Cowdry type A nuclei
May appear identical
Immunohistochemistry or PCR required to
distinguish
When viral cytopathic effect is suspected, a panel of
HSV, VZV, and CMV immunostains are recommended
HSV is more likely to show multinucleation than are
other herpesviruses
MICROSCOPIC PATHOLOGY
Histologic Features
Viral Infections: Morphological Diagnosis of Viral Infections
Epithelial vesicles with viral cytopathic effect
Pustules with neutrophils
Necrosis with little inflammation (fulminant disease)
Cytologic Features
Multinucleation is common
Large cells with classic Cowdry A appearance
Prominent nucleus with viral inclusion
Tzanck test/smear
Sterilely unroofed vesicle is smeared onto a clean
slide
Air dried, fixed with methanol, stained with
available cytology stain
Giemsa, Wright stain, Diff-Quick, Field stain,
methylene blue
Identifies multinucleated cells with viral cytopathic
effect
ANCILLARY TESTS
Immunohistochemistry
HSV antigen targets
Glycoproteins (polyclonal preparations)
Thymidine kinase (monoclonal preparation)
HSV-1 and HSV-2 performed as cocktail
No distinction required for treatment
Overlap of both virus types for all conditions
PCR
Gold standard for diagnosis of central nervous system
HSV infection
Rapid PCR (qualitative) on cerebrospinal fluid (< 24
hours turnaround time)
Therapy instituted with suspected diagnosis
Continued if PCR positive
Discontinued if PCR negative
For tissue biopsies (histology/cytology),
viral cytopathic effect, culture, &/or
I
immunohistochemistry are usually sufficient
Adenovirus
Suspicious viral cytopathic effect
Typically more glassy or smudged in appearance
Other Viral Infections (All Sites)
RNA viruses resulting in necrosis inflammation
Reference testing for confirmation of other viral
infections is recommended
Bacterial Infections (All Sites)
Destructive necrotic lesions
Demonstration of bacteria on Gram or silver stains
Positive cultures of bacteria from sample
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
New onset vesicular rash in an immunosuppressed or
pregnant female
Exaggerated or nonhealing oral ulcer with
superinfection
Pathologic Interpretation Pearls
Histologic diagnoses based on viral cytopathic change
should be confirmed by immunohistochemistry
SELECTED REFERENCES
1. Anderson NW et al: Light microscopy, culture, molecular,
and serologic methods for detection of herpes simplex
virus. J Clin Microbiol. 52(1):2-8, 2014
2. Hoyt B et al: Histological spectrum of cutaneous herpes
infections. Am J Dermatopathol. 36(8):609-19, 2014
3. Grinde B: Herpesviruses: latency and reactivation - viral
strategies and host response. J Oral Microbiol. 5, 2013
4. Steiner I et al: Update on herpes virus infections of the
nervous system. Curr Neurol Neurosci Rep. 13(12):414,
2013
5. Arduino PG et al: Herpes Simplex Virus Type 1 infection:
overview on relevant clinico-pathological features. J Oral
Pathol Med. 37(2):107-21, 2008
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HERPES SIMPLEX VIRUS 1 AND 2 (HSV-1, HSV-2) INFECTIONS
Microscopic Features
Viral Infections: Morphological Diagnosis of Viral Infections
(Left) A large epithelial
cell demonstrates
multinucleation
consistent with herpes
simplex infection. (Courtesy
B. Pritt, MD.) (Right) A liver
at autopsy from fulminant
herpes simplex hepatitis
shows geographic necrosis.
(Left) A liver section from
an autopsy of a patient who
died of disseminated acute
herpes simplex infection with
fulminant hepatitis shows
necrosis adjacent to
what appear to be viable
cells . (Right) HSV1/2
immunohistochemistry from
a fulminant hepatitis case
demonstrates strong nuclear
staining in infected viable
cells as well as areas of
necrosis.
(Left) A example of herpes
simplex multinucleation
is shown with prominent
viral cytopathic effect
and nuclear inclusions.
(Courtesy B. Pritt, MD.)
(Right) Epithelium infected
with herpes simplex virus
demonstrates predominantly
viral nuclear inclusions
with rare multinucleation,
making varicella-zoster virus
also a possibility. (Courtesy
B. Pritt, MD.)
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