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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
KAPOSI SARCOMA-ASSOCIATED HERPESVIRUS (HHV-8) INFECTION
A case of classic Kaposi sarcoma (KS) in an elderly man is
shown. Although uncommon, both flat and nodular
lesions are seen in this case. (From DP: Neoplastic
Viral Infections: Morphological Diagnosis of Viral Infections
Derm.)
TERMINOLOGY
Abbreviations
Human herpesvirus 8 (HHV-8)
Synonyms
Kaposi sarcoma virus, KS agent
Definitions
"Kaposi" from Moritz Kaposi (first described in 1872)
ETIOLOGY/PATHOGENESIS
Infectious Agents
HHV-8
Large double-stranded DNA virus
Found in saliva and semen
Definitive route of transmission remains unknown
Viral infection thought to be necessary but not
sufficient for KS
An immunocompromised state is contributory
In HIV infection, the Tat transcription factor cross
activates viral replication of HHV-8
CLINICAL ISSUES
Epidemiology
4 clinical-epidemiologic forms are recognized
Classical indolent
Affects elderly men of Eastern European or
Mediterranean descent
Cutaneous lesions begin on extremities, enlarge
and spread proximally
Endemic African
Affects children and young adults in sub-Saharan
I
Africa
Variable clinical course: From indolent to locally
infiltrative and aggressive
1
High magnification of a KS lesion of the skin demonstrates
the slit-like spaces filled with blood , the spindle cell
proliferation , and several mitoses .
Generalized lymphadenopathy is common
Iatrogenic
Caused by medically induced immunosuppression
Male predilection
Involves mucocutaneous tissues, lymph nodes,
and viscera
Epidemic AIDS-associated
HIV-positive men who have sex with men have
highest risk
Skin and visceral involvement can be extensive
Skin lesions have a predilection for face and lower
extremities
50% of cases have visceral involvement
GI tract and lungs are 2 most frequent sites for
visceral involvement
Lesions enlarge, multiply in number, and coalesce
with decreasing CD4 count
Presentation
Primary presentation is purple to black flat, raised, or
nodular skin lesions on any body surface
Chronic lesions may show severe crusting, erosion,
ulceration, or superinfection
Internal organs may also be affected (most common
in untreated HIV infection) and present with organspecific symptoms
Liver involvement with transaminitis
Pulmonary involvement with hemoptysis
Gastrointestinal involvement with hematochezia,
hematemesis, melena, or bright red blood per
rectum
Treatment
Surgical approaches
Typically reserved for solitary lesions
Drugs
Highly active antiretroviral therapy (HAART) is
indispensable for epidemic AIDS-associated KS
Some antiretroviral drugs may have anti-HHV8
activity
20
KAPOSI SARCOMA-ASSOCIATED HERPESVIRUS (HHV-8) INFECTION
Viral Infections: Morphological Diagnosis of Viral Infections
Clinical Issues
4 clinical-epidemiologic forms
Classical indolent: Men of Eastern European/
Mediterranean descent
Endemic African: Children and young adults in
sub-Saharan Africa
Iatrogenic: Patient with medical
immunosuppression
Epidemic: AIDS-associated
Macroscopic Pathology
Patches, plaques, and nodules
Pink to purple-red to black in color
Small and solitary to numerous and coalescing
Microscopic Pathology
3 well-defined stages of disease
Systemic chemotherapy (vincristine)
Reserved for severe, widespread, symptomatic or
rapidly progressive disease
Local therapy
Topical chemotherapeutics, liquid nitrogen,
radiotherapy
Safe, cost-effective option for patients with limited
cutaneous disease
Useful adjunct therapy for progressive disease
unresponsive to chemotherapy
Prognosis
Varies by clinical-epidemiologic form
Late stage KS in HIV-infected patients without
treatment has poor prognosis
IMAGE FINDINGS
Radiographic Findings
Pulmonary involvement: Nodular or reticular opacities
with predilection for perihilar and lower lung fields
Gastrointestinal involvement: Nodular opacities
Lymphadenopathy may or may not be present
MACROSCOPIC FEATURES
General Features
Patches, plaques, and nodules that vary in color from
pink to purple-red to black
Mucocutaneous lesions my show associated
lymphedema and scale
Wide variation in number and size of lesions
MICROSCOPIC PATHOLOGY
Histologic Features
All clinical forms share histologic features
Non-HIV cases may show greater anaplastic features
and mitoses
Key Facts
Ancillary Tests
Lesional cells positive for immunohistochemical
markers of vascular endothelium: CD31, CD34, FLI-1,
ERG
HHV8 is a sensitive and specific
immunohistochemical marker of KS
Cytologic Features
Numerous described histologic variants
Patch Stage
Promontory sign: Vascular proliferation that dissects
around skin adnexa and larger ectatic vessels
Proliferation of endothelial-lined vessels present in
dermis
Histologic findings may be subtle
Hemosiderin-laden macrophages
Extravasated red blood cells
Sparse chronic inflammatory infiltrate: Lymphocytes
and plasma cells
Rare spindled cell component
Plaque Stage
Skin lesions involve most of dermis, may extend to
subcutis
Represents an exaggeration of patch stage
Hyaline globules easily found
Chronic inflammatory infiltrate
Nodular Stage
Well-circumscribed intersecting fascicles of uniform
spindled cells
Mitoses may be numerous
Mild cytologic atypia may be present
Slit-like vascular spaces with extravasated
erythrocytes/hyaline globules
Patch: Increased vascular spaces, chronic
inflammatory infiltrate
Plaque: More extensive vascular proliferation,
greater component of spindled cells, hyaline
globules
Nodular: Well-circumscribed intersecting fascicles
of sieve-like vascular spaces and spindled cells,
hyaline globules, frequent mitoses, mild cytologic
atypia
HIV-related cases may show more extensive
dissecting vessels
Anaplastic, lymphangioma-like, lymphangiectatic,
hyperkeratotic, keloidal, micronodular
Not pathognomonic of KS
Endothelial cells are flat and uniform
Greater component of spindled cells
Eosinophilic material
Intra- or extracellular location
Consists of fragment erythrocytes
More frequently found in AIDS-associated KS
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KAPOSI SARCOMA-ASSOCIATED HERPESVIRUS (HHV-8) INFECTION
A
Cytological Features
Bland flat and spindled endothelial tumor cells
ANCILLARY TESTS
Histochemistry
Hyaline globules are positive for PAS
Iron stain highlights intra- and extracellular
hemosiderin deposition
Immunohistochemistry
Vascular channels and spindled cells are positive for
vascular endothelial markers
CD31, CD34: Membranous and cytoplasmic
reactivity
ERG, FLI-1: Nuclear reactivity
HHV8 is a highly sensitive and specific marker of KS
Lesional vascular spaces are not surrounded by SMA(+)
pericytes
Viral Infections: Morphological Diagnosis of Viral Infections
DIFFERENTIAL DIAGNOSIS
Hobnail Hemangioma
Solitary vascular lesions
Biphasic growth
Dilated vessels in superficial areas that narrow with
increasing dermal depth
Hobnail endothelial cells
HHV8(-)
Capillary Hemangioma
Lobular growth of narrow capillaries
HHV8(-)
Spindle Cell Hemangioma
KS-like features coincident with cavernous
hemangioma-like features
No increased mitoses
Scattered epithelioid tumor cells
HHV8(-)
ngiosarcoma
Anastomosing vascular structures
Endothelial multilayering
Prominent nuclear atypia
HHV8(-)
Tufted Hemangioma
Cannonball distribution of vascular tufts
Endothelial cells are surround by SMA (+) pericytes
Crescent shaped clefts
HHV8(-)
Lymphangiomatosis (of Limbs)
Solitary, plaque-like lesions
No increased mitoses
No prominent inflammatory infiltrate
HHV8(-)
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Age distribution
Gross appearance
Organ distribution
Pathologic Interpretation Pearls
All clinical-epidemiologic forms show similar
histologic features
Histologic findings: Sieve-like vascular spaces, spindled
cells, chronic inflammation, hyaline globules,
hemosiderin
HHV8 expression by IHC is a sensitive and specific
marker of KS
SELECTED REFERENCES
1. Rohner E et al: HHV-8 seroprevalence: a global view. Syst
Rev. 3:11, 2014
2. Fatahzadeh M et al: Oral Kaposi’s sarcoma: a review and
update. Int J Dermatol. 52(6):666-72, 2013
3. Radu O et al: Kaposi sarcoma. Arch Pathol Lab Med.
137(2):289-94, 2013
4. Ruocco E et al: Kaposi’s sarcoma: etiology and
pathogenesis, inducing factors, causal associations, and
treatments: facts and controversies. Clin Dermatol.
31(4):413-22, 2013
5. Patel RM et al: Immunohistochemical detection of human
herpes virus-8 latent nuclear antigen-1 is useful in the
diagnosis of Kaposi sarcoma. Mod Pathol. 17(4):456-60,
2004
6. Hong A et al: Immunohistochemical detection of the
human herpes virus 8 (HHV8) latent nuclear antigen-1 in
Kaposi’s sarcoma. Pathology. 35(5):448-50, 2003
7. O’Hara CD et al: Endothelial lesions of soft tissues: a review
of reactive and neoplastic entities with emphasis on lowgrade malignant ("borderline") vascular tumors. Adv Anat
Pathol. 10(2):69-87, 2003
8. Ioachim HL et al: Kaposi’s sarcoma of internal organs. A
multiparameter study of 86 cases. Cancer. 75(6):1376-85,
1995
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Kaposiform Hemangioendothelioma
Usually infants and young children
Retroperitoneal and abdominal location
Infiltrative cellular lobules
No increased mitoses
HHV8(-)
KAPOSI SARCOMA-ASSOCIATED HERPESVIRUS (HHV-8) INFECTION
p
p
p
Microscopic Features
Viral Infections: Morphological Diagnosis of Viral Infections
(Left) Patients with AIDSrelated KS may present with
lesions at unusual anatomic
sites, as did this patient who
developed small reddish
lesions on his upper eyelid.
In patients with darker
skin, lesions may be very
subtle. (From DP: Neoplastic
Derm.) (Right) KS lesions
of the oral mucosa (hard
alate) are shown , which
may be difficult to detect.
Kaposi sarcoma can involve
any part of the body and
extensive internal disease has
high mortality. (From DP:
Head & Neck.)
(Left) Low magnification
in a case of nodular KS in
the skin demonstrates the
tumor cells admixed
with edema and areas
of hemorrhage . (Right)
Medium magnification of a
KS shows the slit-like spaces
and the spindle cell
roliferation .
(Left) Immunohistochemistry
for human herpesvirus 8,
the virus responsible for
KS, reveals strong nuclear
staining within the KS
lesion of the skin. (Right)
High magnification of a KS
lesion demonstrates the
slit-like spaces filled with
blood , the spindle cell
roliferation , several
mitoses , and conspicuous
hyaline bodies
the cytoplasm, which are
strongly PAS positive.
within
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MEASLES VIRUS INFECTION
Section of lung from an autopsy shows multinucleated
cells containing eosinophilic cytoplasmic and
nuclear inclusions with perinuclear halos that are
Viral Infections: Morphological Diagnosis of Viral Infections
characteristic of measles virus infection.
TERMINOLOGY
Synonyms
Rubeola, morbilli, English measles
Definitions
"Masel" (Middle Dutch): "pustule"
Paramyxoviridae family: "Para-" derived from "beyond"
and "myxo-" derived from "mucus"
ETIOLOGY/PATHOGENESIS
Infectious Agents
Highly contagious: 90% of nonimmune will become
infected when exposed to respiratory droplets
Infects dendritic cells in alveoli, then lymph node
lymphocytes, then hematologic spread to skin, lung,
liver, spleen, and brain
Cell receptors: CD46 (all nucleated cells) and CD150/
SLAM (signaling lymphocyte activation molecule)
(activated T- and B-lymphocytes)
Incubation period: 7-21 days
Contagious period: Duration of rash plus 4 days before
and after rash is visible
Warthin-Finkeldey giant cells contain multiple nuclei
with eosinophilic nuclear inclusions and are characteristic
of, but not exclusive to, infection with measles virus.
Prodrome: Mild to moderate fever, cough, coryza,
conjunctivitis, and Koplik spots (pathognomonic)
on buccal mucosa
Maculopapular rash spreading from face to trunk
and extremities (14 days after exposure) with high
fever (> 40 C)
Acute encephalitis (1 per 1,000)
Subacute sclerosing panencephalitis (SSPE): 7-10 years
following infection
Laboratory Tests
Serology (IgG and IgM)
RT-PCR (oropharyngeal, nasal, or nasopharyngeal
swab; urine)
Natural History
Typically self-limited
Risk of SSPE post infection
Treatment
Primary prevention
Measles, mumps, rubella (MMR) vaccine (doses at
12-15 months and 4-6 years)
Post-exposure prophylaxis for nonimmune
MMR (within 72 hours); IgG (< 6 days)
Active infection: Supportive care
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CLINICAL ISSUES
Epidemiology
Worldwide: 20 million cases per year (164,000 deaths)
United States: 37-220 cases per year (2000-2013); ~
550,000 cases per year (500 deaths) (pre-1963)
Site
Skin, lung, lymph node, brain
Presentation
Primary infection
Prognosis
Primary infection
Symptoms typically resolve after 7-10 days
1-2 per 1,000 die from respiratory and neurological
complications
SSPE: Progressive neurological decline and death (1-2
years)
MICROBIOLOGY
Virus Features
Enveloped, single-strand RNA virus
100-300 nm in size, with helical nucleocapsid
MEASLES VIRUS INFECTION
Etiology
Highly contagious and transmitted through
respiratory droplets
Clinical Issues
Incidence: Increasing, with 603 cases in USA (Jan-Oct
2014) due to decreased vaccination rates
Prodrome with mild to moderate fever, cough,
coryza, conjunctivitis, and Koplik spots
Maculopapular rash and high fever (> 40 C)
15,894 nucleotides encoding 6 genes (7 proteins)
Culture
Grows in cell culture (1-2 weeks)
VERO/hSLAM or B95a
Key Facts
Typically self-limited but 1 per 1,000 die from
respiratory or neurological complications
SSPE rarely occurs after 7-10 years
Microscopic Pathology
Eosinophilic nuclear and cytoplasmic inclusions
Warthin-Finkeldey giant cells
Confirm diagnosis with immunohistochemistry &/or
culture
ANCILLARY TESTS
Immunohistochemistry
Anti-measles abs
Viral Infections: Morphological Diagnosis of Viral Infections
MACROSCOPIC FEATURES
Oral Mucosa
Koplik spots (3 days before rash)
Skin
Generalized maculopapular erythematous eruption
MICROSCOPIC PATHOLOGY
Histologic Features
Skin: Spongiotic epidermis with vesiculation;
keratinocytes with degenerative changes
Lymph nodes: Follicular hyperplasia
Lungs: Bronchiolitis to pneumonia and diffuse
alveolar damage
Brain: Perivascular inflammation, gliosis, loss of
neurons; eosinophilic nuclear inclusions
Cytologic Features
Eosinophilic cytoplasmic inclusions and intranuclear
inclusions with clear halo
Warthin-Finkeldey giant cells
IMAGE GALLERY
DIFFERENTIAL DIAGNOSIS
Infections Presenting With Fever and Rash
Rubella, scarlet fever (Streptococcus pyogenes), erythema
infectiosum (parvovirus B19), meningococcemia,
typhoid fever, varicella
Lack of Koplik spots or serum measles IgM
Giant Cell-Associated Viral Infections
CMV, HSV, VZV, RSV, parainfluenza
Lack of staining by antimeasles IHC
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Measles IHC &/or culture confirm diagnosis
Distinguish vaccine strain from wild type by
genotyping
Lack of vaccination history
SELECTED REFERENCES
1. Moss WJ et al: Measles. Lancet. 379(9811):153-64, 2012
(Left) Warthin-Finkeldey giant cells in lung parenchyma contain multiple nuclei with eosinophilic inclusions and clear halos. (Center) Warthin-
Finkeldey giant cells
(From DP: Neuropathology.)
in lymph nodes contain multiple nuclei. (Right) Glassy nuclear viral inclusions are typical in brain tissue in SSPE.
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PARVOVIRUS B19 INFECTION
This high-power photomicrograph of a placenta from
a case of nonimmune hydrops fetalis shows nucleated
erythrocytes with intranuclear parvovirus inclusions .
Viral Infections: Morphological Diagnosis of Viral Infections
TERMINOLOGY
Synonyms
Parvo, erythema infectiosum, 5th disease, "slapped
cheek disease"
Definitions
Latin: "Parvo" (small)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Parvovirus, from Parvovirididae family, genus
Erythrovirus
Single-stranded DNA virus
Globoside or erythrocyte P antigen is necessary for
infection of host cells
Transmission
Primarily via respiratory droplets but also vertical
from mother to fetus
Stem cell and organ transplantation or blood
transfusion products (rare)
Virus propagates in erythroid precursors
CLINICAL ISSUES
Presentation
Erythema infectiosum
Children
Prodrome: Fever, chills malaise, headache
Slapped-cheek appearance
Stocking/glove maculopapular rash, spreads to
trunk and becomes reticular
Adults
Arthritis: Immune complex mediated; women >
I
men
Transient aplastic crisis
Hypoproliferative anemia
1
Previable fetus with hydrops secondary to parvovirus
infection is shown. (From DP: Placenta.)
Occurs in setting of coincident hemolytic anemia
Hereditary spherocytosis, thalassemia,
autoimmune hemolytic anemia
Varying degree of neutropenia and
thrombocytopenia
Pure red cell aplasia
Caused by chronic infection in
immunocompromised patients
Congenital infection
Vertical transmission occurs in 33% of women with
primary infection during pregnancy
Causes nonimmune hydrops 4 weeks after infection
Severe anemia and high cardiac output that may
lead to fetal death
Fetus is highly susceptible to viral infection of
erythroid precursors
Viral myocarditis that contributes to cardiac
dysfunction
Viral myocarditis and dilated cardiomyopathy (adults
25-65 years of age)
Treatment
IVIG may resolve anemia in immunocompromised
patients
Transfusions in patients with severe anemia
Intrauterine transfusion for fetal anemia
Prognosis
5-10% of in utero cases will result in lethal hydrops
fetalis
Maternal seroconversion provides lifetime maternal
immunity
IMAGE FINDINGS
Ultrasonographic Findings
May detect fetal hydrops (FH)
Skin edema, fluid in serous cavities,
polyhydramnios, and thickened placenta
26
PARVOVIRUS B19 INFECTION
Etiology
Single-stranded DNA virus transmitted by respiratory
droplets and replicates in erythroid precursor cells
Clinical Issues
Erythema infectiosum: Stocking/glove rash and
"slapped cheek"
Transient aplastic crisis: Anemia with symptoms
Pure red cell aplasia: Chronic anemia in
immunocompromised patients
Key Facts
Fetal hydrops with 5-10% mortality for fetus
Microscopic Pathology
Nucleated peripheral red blood cells with inclusions
Giant erythroblasts and pronormoblasts with
inclusions
Ancillary Tests
Immunohistochemistry or PCR is definitive
Viral Infections: Morphological Diagnosis of Viral Infections
MACROSCOPIC FEATURES
Fetal Hydrops
Fetus with edema, pallor, cardiomegaly, hepatomegaly
and a thick, pale, friable placenta
MICROSCOPIC PATHOLOGY
Histologic Features
Peripheral blood: Normochromic/normocytic anemia
Normal erythrocyte morphology (unless patient has
underlying constitutional anemia)
Bone marrow
Severe erythroid hypoplasia
Rare atypical erythroblasts and pronormoblasts
Giant in size, intranuclear inclusions,
multinucleation
Fetus
Hypocellular bone marrow and extramedullary
hematopoiesis (EMH)
Atypical pronormoblasts in bone marrow or sites of
EMH
Hemosiderosis
Placenta
Diffuse villous edema with increased nucleated red
blood cells with intranuclear inclusions
ANCILLARY TESTS
Immunohistochemistry
Positive reactivity with parvovirus-specific antibodies
PCR
May detect early infection prior to appearance of
serum IgM
Serologic Testing
IgG and IgM antibodies to parvovirus
DIFFERENTIAL DIAGNOSIS
Rubella
PCR-based and serologic testing will differentiate
Erythroblastosis Fetalis
Immune-mediated hemolysis, lacks viral inclusions
May be a clinical history of Rh factor incompatibility
Chronic Maternal Fetal Transfusion
Fetal hydrops, no viral inclusions
Fetal blood in intervillous blood space of placenta
Positive Kleihauer-Betke stain on maternal blood
SELECTED REFERENCES
1. Rogo LD et al: Human parvovirus B19: a review. Acta Virol.
58(3):199-213, 2014
IMAGE GALLERY
(Left) Immunohistochemical detection is a useful adjunct assay to confirm suspected cases of parvovirus infection (placenta). (Center)
Despite postmortem autolysis, bone marrow specimen from a fetus infected with parvovirus shows marked hypocellularity. (Right) A giant
proerythroblast ("lantern cell") is shown in a patient with parvovirus B19 infection (aspirate). A nuclear viral inclusion is present with
minimal erythroid maturation. (From DP: Nonneoplastic Pediatrics.)
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POLYOMAVIRUS INFECTIONS
Glial cells with eosinophilic nuclear inclusions are
indicative of JC virus infection and are characteristic of
progressive multifocal leukoencephalopathy. (Courtesy
R. Folkerth, MD.)
Viral Infections: Morphological Diagnosis of Viral Infections
TERMINOLOGY
Definitions
Polyomaviridae derived from "poly" many and "oma"
tumors
Viral names are derived from orgin of virus
JC = John Cunningham (patient)
WU = Washington University (location)
Family Members
JC polyomavirus (JCV)
Progressive multifocal leukoencephalopathy
BK polyomavirus (BKV)
Polyomavirus-associated nephropathy
Hemorrhagic cystitis
Karolinska Institute polyomavirus (KIPyV)
No disease association
Washington University polyomavirus (WUPyV)
No disease association
Merkel cell polyomavirus (MCPyV)
Merkel cell carcinoma
Human polyomavirus 6 (HPyV6)
No disease association
Human polyomavirus 7 (HPyV7)
No disease association
Trichodysplasia spinulosa-associated polyomavirus
(TSPyV)
Trichodysplasia spinulosa, pilomatrix dysplasia
Human polyomavirus 9 (HPyV9)
No disease association
Malawi polyomavirus (MWPyV)
No disease association
St. Louis polyomavirus (STLPyV)
No disease association
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1
Decoy cells are nonneoplastic tubular epithelial cells
infected with BK virus, characterized by enlarged nuclei
with glassy basophilic nuclear inclusions.
ETIOLOGY/PATHOGENESIS
Infectious Agents
Ubiquitous; spread person to person
Polyomavirus nephropathy (PVN)
Reactivation of BK virus (80%) or JC virus (20%) in
tubular epithelial cells
Merkel cell carcinoma (MCC)
Clonal integration of Merkel cell polyomavirus
(MCPyV) in Merkel cells (80%)
Large T tumor antigen (LT) and small tumor antigen
(sT) target tumor suppressor genes
Progressive multifocal leukoencephalopathy (PML)
Reactivation of JC virus in oligodendrocytes
resulting in demyelination
CLINICAL ISSUES
Epidemiology
Seropositivity in 20-99% of individuals (variation with
specific virus and population)
PVN
5% of kidney transplant patients with tacrolimus/
mycophenolate
Merkel cell carcinoma
0.6 per 100,000; increases with sun exposure, age
(median: 70), and immunosuppression
Progressive multifocal leukoencephalopathy
Immunosuppression due to HIV/AIDS, solid
organ transplant, monoclonal antibodies (i.e.,
natalizumab, rituximab)
Site
Kidneys
Skin
Brain
Presentation
Primary infection
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POLYOMAVIRUS INFECTIONS
Viral Infections: Morphological Diagnosis of Viral Infections
Etiology
Ubiquitous viruses (20-99% seropositivity)
Clinical Issues
Polyomavirus nephropathy (BKV, JCV)
Acute renal failure, hemorrhagic cystitis, and uretal
obstruction
PCR BKV (urine) and decoy cells (urine cytology)
Merkel cell carcinoma (MCPyV)
Rapidly growing, nontender, red to violaceous, firm
intradermal nodule positive lymph nodes and
distant metastases
Progressive multifocal leukoencephalopathy (JCV)
Weakness, vision loss, impaired speech, and
cognitive deterioration
PCR JCV (CSF, brain tissue)
No direct antiviral treatment available
Mild respiratory infection and fever, or
asymptomatic
PVN
Acute renal failure, hemorrhagic cystitis, and uretal
obstruction
MCC
Rapidly growing, nontender, red to violaceous, firm
intradermal nodule
Positive lymph nodes and distant metastases may be
present
PML
Weakness, vision loss, impaired speech, and
cognitive deterioration
Laboratory Tests
JCV
PCR (urine, plasma, CSF, brain tissue)
BKV
PCR (urine, plasma)
Decoy cells (urine cytology)
Key Facts
Microscopic Pathology
PVN: Interstitial mononuclear inflammation,
tubulitis; intranuclear inclusions in tubular
epithelium
MCC: Dermal nodule of small round blue cells with
large prominent nuclei, scant cytoplasm, diffusely
dispersed chromatin, and numerous mitoses
PML: Multifocal demyelination with relative axon
sparing, loss of oligodendrocytes, and macrophages
in area of demyelination; enlarged, glassy, darkstaining inclusions
Ancillary Tests
Antipolyomavirus Abs (SV40 large T antigen)
Prognosis
PVN
MCC
PML
MICROBIOLOGY
Virus Features
Nonenveloped, circular, double-stranded DNA virus
40-45 nm, icosahedral
~ 5,200 bp genome (6 genes)
MACROSCOPIC FEATURES
Decrease immunosuppression (PVN and PML)
Surgery and radiation (MCC)
Graft loss dependent on stage at diagnosis
Residual impairment of renal function common
5-year disease-associated mortality is 46%
Stability or improvement with HAART
Residual deficits depending on location of lesions
Natural History
PVN
Can lead to renal failure; loss of transplant
MCC
Local recurrence and distant metastasis common
PML
Can lead to rapid deterioration and death
Treatment
No direct antiviral treatment available
PVN
Decrease immunosuppression
Cidofovir, leflunomide
MCC
Wide local excision, sentinal node biopsy,
fractionated radiation
Limited role for chemotherapy
Emerging role for molecular targeted therapies
PML
HAART; decrease immunosuppression
Plasma exchange for monoclonal antibodies
PVN
Streaky fibrosis of medulla and circumscribed cortical
scars
MCC
Tumor fills entire dermis with sparing of epidermis
PML
Small demyelinating lesions at cortical gray-white
matter junction that coalesce to occupy large volume
of white matter
MICROSCOPIC PATHOLOGY
Histologic Features
PVN
Interstitial mononuclear inflammation
Tubulitis and tubular injury
MCC
Expansile dermal nodule with subepidermal
aggregates of tumor cells
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