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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
ZOONOTIC NEMATODE INFECTIONS
Life Cycle
Ancylostoma cycle between mammals and
environment and are species specific in their
pathology
Angiostrongylus cycle between snails/slugs and rats
Anisakis cycles between crustaceans, fish/squid, and
sea mammals (dolphins)
Helminthic Parasitic Infections: Nematodes
Baylisascaris cycles between raccoons and environment
with other mammals as possible hosts
Dirofilaria cycle between mammals and mosquitos
Gnathostoma cycle between copepods, fish/frogs,
seabirds, and pigs/dogs/cats
Toxocara cycle in dogs (similar to Ascaris in humans),
but may also pass through rabbits and other wild
animals
Trichinella cycle between pigs (domestic) or bears
(sylvatic) and rodents (both) with adult worms in
intestine releasing larvae that move into muscle tissue
to encyst
Filariform (infective) larva passes into human skin,
fails to migrate into deep tissues, wanders aberrantly
Humans ingest food containing 3rd-stage larvae,
which migrate through tissue and mature
(incompletely) in meninges or gut
L3 larvae from undercooked fish enter human
intestine, burrow aberrantly, and fail to mature or
excrete eggs
Humans ingest embryonated eggs, larvae hatch
and migrate through tissues, growing in size and
wandering unrestricted, causing inflammation
Humans are bitten by infected mosquitos, L3 larva
migrates (usually a single worm) through tissue and
usually dies, causing eosinophilic inflammation
L3 larvae from undercooked fish enter human
intestine, burrow aberrantly, and fail to mature or
excrete eggs
L3 larvae burrow out of gastrointestinal tract and
can be found in skin, other organs, brain, and soft
tissue
Humans ingest embryonated eggs accidentally,
developing larvae migrate through tissues but
cannot mature or excrete eggs
Humans ingest undercooked pig or bear meat with
cysts, worm completes its life cycle and releases
larvae, which encyst in human skeletal muscle
ANCILLARY TESTS
Parasite Reference Testing
Although most zoonoses are self-limited and many do
not require further treatment once removed surgical,
complete speciation may be required for patient peace
of mind
Specialized laboratories (e.g., Centers for Disease
Control, Atlanta, GA) have morphological expertise
available to speciate as well as possible
Molecular tests can be applied to classify existing or
new species that may be found
DIFFERENTIAL DIAGNOSIS
Malignancy
Most common reason lung, soft tissue, and lymph
node masses are biopsied is for fear of malignancy
Larva Currens (Strongyloides stercoralis)
Autoinfectious complication of a human infection
with S. stercoralis (non-zoonotic)
Worms are directly invading host from colon
Rapidly moving and has perianal involvement with
more expansive urticaria
Tumoral Calcinosis
Collections of calcium may mimic calcified worm but
should have limited inflammation and no eosinophils
Cysticercosis/Echinococcosis
Ruptured or remote cysts of either disease may appear
as solitary masses in any site but should contain
hooklets
Schistosomiasis
Calcified and granulomatous response around eggs
may mimic worm cross sections, but granulomas are
often exuberant and spines on eggs can be identified
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Clinical exposure history is often supportive of
nematodes in tissue, but many cases may have no
obvious exposure, requiring more careful analysis
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MICROSCOPIC PATHOLOGY
Histologic Features
Cross sections of living larvae or adult nematodes with
variable neutrophilic/eosinophilic inflammation and
necrosis
Size of worm, location, and internal and external
structures are key to speciation
Eosinophilic granulomatous inflammation with
central degenerated dead nematode structures
Splendore-Hoeppli phenomenon and CharcotLeyden crystals may be present
Identification of species may be difficult or
impossible if structures are not intact
Pathologic Interpretation Pearls
Fragments of material that do not appear to be of
human origin with eosinophils should be evaluated as
a possible helminth
SELECTED REFERENCES
1. Prickett KA et al: Helminths: a clinical review and update.
Semin Cutan Med Surg. 33(3):128-32, 2014
2. Finsterer J et al: Parasitoses of the human central nervous
system. J Helminthol. 87(3):257-70, 2013
3. Pilsczek FH: Helminthic infections mimicking malignancy:
a review of published case reports. J Infect Dev Ctries.
4(7):425-9, 2010
Microscopic Features
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Helminthic Parasitic Infections: Nematodes
ZOONOTIC NEMATODE INFECTIONS
(Left) A submucosal mass
in the stomach from
a patient with a long
history of homemade sushi
ingestion demonstrates large
eosinophilic granulomas
with cross sections of
degenerated worm .
(Right) Cross section
of a dead, degenerated
worm is surrounded by
eosinophilic granuloma with
rominent Charcot-Leyden
crystals .
(Left) Large eosinophilic
ranulomas were found
in the mesentry of this
atient with no obvious
exposures who was thought
to have a malignancy.
Despite multiple levels,
fragments of nematode were
found but no species-specific
features were identified.
Note the empty spaces,
which probably contained
the worm previously. (Right)
High magnification of the
center of an eosinophilic
ranuloma shows residual
ortions of nematode cuticle
although speciation was
not possible.
(Left) A soft tissue mass
removed from a patient
with no obvious exposures
demonstrates a cuticle
structure within
otherwise unidentifiable
worm material, consistent
with a nematode. (Right)
testicular mass removed
for a patient with mosquito
exposure demonstrates cross
sections of a dead nematode
. Elsewhere, rupture and
release of sperm into soft
tissue with inflammation
was found. The species was
not identified but could
be Wucheria or a zoonotic
species.
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SECTION 2
Schistosomiasis V-2-2
V-2-8
Helminthic Parasitic Infections: Trematodes
SCHISTOSOMIASIS
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High magnification of a bladder section (trichrome stain)
shows multiple oval and elongated eggs embedded in
granulation tissue. A terminal spine is present on an
egg, consistent with S. hematobium.
TERMINOLOGY
Synonyms
Bilharziasis, snail fever, Katayama fever
Definitions
Greek: "Skhistos" (divided, cloven) + "soma" (body)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Parasitic trematode worms (flukes) of Schistosoma
genus
Species reported to cause infections in humans
3 major species: Schistosoma mansoni, Schistosoma
haematobium, Schistosoma japonicum
Less common species: e.g., Schistosoma mekongi,
Schistosoma intercalatum
Association of Schistosoma spp. with diseases of organ
systems
S. mansoni and S. japonicum: Diseases in intestines
and liver
S. haematobium: Diseases in genitourinary tract
Less common species: e.g., S. mekongi and S.
intercalatum can cause diseases in intestines and liver
Pathogenesis
Life cycle
Schistosoma eggs are seeded into fresh water through
urine or feces from infected humans or animals
Eggs release miracidia, which penetrate into snails
Each Schistosoma sp. is associated with a specific
snail species, distribution of which determines
geographic distributions of individual Schistosoma
spp.
Cercariae (infectious larvae form) are produced
inside snail host, which are then released into water
Humans/animals become infected when skin is
penetrated by cercariae in contaminated water
Medium magnification of a lung section (H&E) shows a
Schistosoma egg trapped in a granuloma surrounded
by chronic inflammation. Eosinophilic infiltrate is present
within and around the granuloma.
Cercariae penetrate human skin, become
schistosomula, and migrate through circulation
until they reach the liver, where they mature into
adult worms
Worms stay in bowel/rectum venules (S. mansoni
and S. japonicum) or venous plexus in bladder (S.
haematobium)
Eggs are deposited in the tissue
Eggs then move toward lumen of intestine, or
bladder and ureters, and are then eliminated in
feces or urine, respectively
Pathology is caused by host responses against antigens
of Schistosoma eggs, which induce predominantly
Th-2 immune response, resulting in an eosinophilic
granulomatous reaction
Eggs may embolize to liver, spleen, lungs, brain, or
spinal cord, and less commonly skin and peritoneal
surfaces
Extent of pathology depends on worm burden, host
genetic background, and parasite strains
CLINICAL ISSUES
Epidemiology
Worldwide distribution
Prevalence is highest in sub-Saharan Africa, where 85%
of total burden is found
Endemic distributions of different Schistosoma spp.
S. mansoni: Mostly in Africa and South America
S. haematobium: Mostly in Africa and Middle East
S. japonicum: Mostly in East Asia
S. mekongi: Mostly in Laos, Cambodia
S. intercalatum: Mostly in West and Central Africa
Presentation
Migratory infection or immediate manifestations
Maculopapular eruption at site of cercarial
penetration
Cercarial dermatitis ("swimmer’s itch")
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SCHISTOSOMIASIS
Etiology
Parasitic trematode worms (flukes) of genus
Schistosoma
3 major species causing human infections:
Schistosoma mansoni, Schistosoma haematobium,
Schistosoma japonicum
Pathology is caused by host tissue reactions
against antigens of Schistosoma eggs, which induce
predominantly Th-2 immune responses
Clinical Issues
Worldwide distribution; prevalence is highest in subSaharan Africa
Mortality related to schistosomiasis is low
Likelihood of complications and morbidity correlate
with parasite burden, duration of infection, site(s) of
infection
Key Facts
Microscopic Pathology
Inflammatory granulomatous reaction and
eosinophilic infiltration, which result in local tissue
destruction and fibrosis
S. mansoni (average: 140 x 66 m): Elongated/oval egg
with a lateral spine
S. haematobium (average: 143 x 60 m): Elongated/
oval egg with a terminal spine
S. japonicum (average: 90 x 70 m): Oval egg with a
small lateral spine/knob
Top Differential Diagnoses
Strongyloidiasis
Tuberculosis
Coccidioidomycosis
Neoplasms, sarcoidosis
Helminthic Parasitic Infections: Trematodes
Maculopapular skin eruption with pruritus after
repeated contacts with parasites; mostly associated
with larvae of bird schistosomes of Trichobilharzia
spp.
Acute infection (Katayama fever)
Hypersensitivity reaction to schistosome antigens
and circulating immune complexes; occurs 3-8
weeks after exposure
Associated with eosinophilia
Symptoms are variable, e.g., fever, urticaria and
angioedema, arthralgias, diarrhea, abdominal pain
Chronic infection
Occurs in response to cumulative deposition of eggs
in tissues, and the resulting host reactions
Intestinal infection
Most common symptoms: Abdominal pain,
diarrhea
Heavy infections: Intestinal bleeding and iron
deficiency anemia
Hepatosplenic infection
In adults, chronic infection leads to periportal
fibrosis, resulting in portal hypertension,
splenomegaly, portocaval shunting, and
gastrointestinal varices
Coinfection of hepatitis B/hepatitis C and
schistosomiasis is reported to cause more severe
disease and worse prognosis than those infected
with either of the pathogens alone
Urinary tract infection
Early infection: Hematuria with eggs excreted in
urine
Early chronic infection: Granulomatous
inflammation and ulcerations result in
development of pseudopolyps, which may mimic
malignancy
Longstanding infection: Fibrosis and calcification
of bladder wall, bladder neck obstruction;
associated with bacterial superinfection, acute
renal failure, and development of bladder cancer
Genital tract infection
Women: Hypertrophic &/or ulcerative lesions of
cervix, vagina, or vulva; involvement of ovaries or
fallopian tubes may lead to infertility
Men: Infection may involve epididymis, testicles,
spermatic cord, or prostate
Reported to be a risk factor for HIV infection in
endemic areas
Pulmonary infection
Occurs mostly as complications in patients
with hepatosplenic infection, which leads to
embolization of Schistosoma eggs into pulmonary
circulation
Progression of disease can result in granulomatous
pulmonary endarteritis, pulmonary hypertension,
and cor pulmonale
Central nervous system infection
Results from embolization of eggs/egg-laying
worms to spinal cord or cerebral microcirculation
Myelopathy is more common than cerebral
disease
Brain involvement may present as single or
multiple intracerebral lesions
Treatment
Generally treated with praziquantel
Reexamination of feces or urine after treatment is
recommended to assess efficacy
Prognosis
Mortality related to schistosomiasis is low
Likelihood of complications and morbidity correlate
with parasite burden, duration of infection, sites of
infection
IMAGE FINDINGS
Radiographic Findings
Chest: Fine miliary nodules corresponding to
granulomatous reactions to Schistosoma eggs
Bladder: Eggshell calcification in submucosa of bladder
and ureteral wall in longstanding infection
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SCHISTOSOMIASIS
Helminthic Parasitic Infections: Trematodes
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CT Findings
Liver: Septal calcifications aligned perpendicularly
to liver capsule produce characteristic "turtle back"
appearance of hepatic schistosomiasis
MACROSCOPIC FEATURES
Gross Examination
Liver: Symmer clay pipestem fibrosis: Enlarged
fibrotic portal tracts with severe portal fibrosis due to
schistosomiasis
Bladder/intestines
"Sandy patches": Masses of calcified ova in mucosa
Polyps or masses: Arise due to granulomatous
inflammation and subsequent fibrosis surrounding
eggs
MICROSCOPIC PATHOLOGY
Histologic Features
Tissue reactions
Inflammatory granulomatous reaction and
eosinophilic infiltration, which result in local tissue
destruction and fibrosis; entrapped ova eventually
die and calcify
Recently laid eggs can cause acute inflammation
Morphology of Schistosoma eggs
S. mansoni (average:140 x 66 m): Elongated/oval
egg with a lateral spine
S. haematobium (average: 143 x 60 m): Elongated/
oval egg with a terminal spine
S. japonicum (average: 90 x 70 m): Oval egg with a
small lateral spine/knob
S. intercalatum (average: 175 x 60 m): Resembles S.
haematobium egg but it is longer, thinner, and has a
longer terminal spine
S. mekongi (average: 69 x 56 m): Spherical egg with
small lateral spine that is not always visible
ANCILLARY TESTS
Ova Detection in Clinical Specimens
Eggs can be detected in urine and stool specimens by
microscopy
Extent of egg shedding may vary widely; multiple
specimens may be needed for diagnosis
Serologic Testing
Commercial assays are available against various
schistosome antigens, e.g., ELISA, radioimmunoassay,
Western blot, complement fixation
Sensitivity and specificity depend on serologic
technique, antigen used, and intensity of infection
Tests are generally negative during acute infection and
turn positive 6-12 weeks after exposure
Cannot distinguish between prior infection and active
disease
Antigen Testing
Qualitative assays that measure parasite antigens in
blood, stool, &/or urine have been developed
Sensitivity and specificity vary with assay techniques
and targeted antigens but are reported to be as good
as or better than stool or urine concentration methods
for egg detection
Molecular Diagnostics
PCR assays for stool, urine, and serum have been
developed but largely remain as research tools
DIFFERENTIAL DIAGNOSIS
Strongyloidiasis
Strongyloides worms and larvae are seen in intestinal
crypts &/or mucosa, often associated with exuberant
eosinophilic infiltration
In intestinal infection, egg-laying Schistosoma worms
are present in microvasculature, while ova are mainly
in submucosa associated with granulomatous reaction
Eosinophilic infiltrate is less intense than that seen
in strongyloidiasis
Coccidioidomycosis
Lacks ova and shows spherules with endospores
Tuberculosis
Positive for acid-fast stain and lacks ova and
eosinophilic inflammation
Sarcoidosis
Lacks presence of ova and eosinophilic inflammation
Neoplasms
Lack ova and exhibit histologic morphologies
consistent with malignant or benign neoplasms
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Inflammatory granulomatous reaction and
eosinophilic infiltration associated with Schistosoma
ova deposition
SELECTED REFERENCES
1. Gryseels B: Schistosomiasis. Infect Dis Clin North Am.
26(2):383-97, 2012
2. Kinkel HF et al: Evaluation of eight serological tests for
diagnosis of imported schistosomiasis. Clin Vaccine
Immunol. 19(6):948-53, 2012
3. Secor WE: The effects of schistosomiasis on HIV/AIDS
infection, progression and transmission. Curr Opin HIV
AIDS. 7(3):254-9, 2012
4. Lapa M et al: Cardiopulmonary manifestations
of hepatosplenic schistosomiasis. Circulation.
119(11):1518-23, 2009
5. Manzella A et al: Schistosomiasis of the liver. Abdom
Imaging. 33(2):144-50, 2008
6. Ross AG et al: Schistosomiasis. N Engl J Med.
346(16):1212-20, 2002
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Microscopic Features
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SCHISTOSOMIASIS
(Left) Clinical photograph
shows swelling of labia
majora
condylomata acuminata.
Follow-up biopsy revealed
schistosomiasis. (Courtesy
M. Ramos-e-Silva, MD,
PhD.) (Right) Medium
magnification of a cervical
biopsy (H&E) shows loads
of viable and degenerated
Schistosoma eggs in a
atient suspected to have
cervical cancer. Remnant
endocervical glands are
seen in association with
tissue inflammation and
destruction .
suggestive of
Helminthic Parasitic Infections: Trematodes
(Left) Very high
magnification of this liver
section (H&E) shows a
Schistosoma egg with a small
lateral spine , consistent
with S. japonicum. (Right)
Very high magnification of
this tissue section (H&E)
shows 2 Schistosoma
eggs. Both ova manifest
a small "hook" in the
shell, corresponding to
a small lateral knob. The
morphology is consistent
with S. japonicum.
(Left) High magnification
of this intestinal section
(H&E) shows 2 Schistosoma
eggs associated with
confluent eosinophilic
and chronic inflammation.
Both ova exhibit prominent
lateral spines , consistent
with S. mansoni. (Right)
Medium magnification of
this liver section (H&E)
shows multiple Schistosoma
mansoni eggs in different
orientations, surrounded by
ranulomatous inflammation
and fibrosis. One egg
appears calcified and
exhibits a prominent lateral
spine .
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(Left) Medium magnification
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of a periintestinal lymph
node section shows multiple
small, spherical, calcified
Schistosoma eggs in a patient
with infection of S. mekongi
in the jejunal mucosa. (Right)
High magnification of a
bladder biopsy shows multiple
elongated Schistosoma eggs
containing viable miracidia.
The abundance of eosinophils
suggest possibly an acute
Helminthic Parasitic Infections: Trematodes
infection. A terminal spine
is present on an egg, consistent
with S. hematobium.
(Left) Medium magnification
of a bladder biopsy reveals
schistosomiasis associated
with prominent granulomatous
reaction as well as chronic
and eosinophilic inflammation.
Multiple empty egg shells
, some being engulfed by
multinucleated giant cells
, are present. (Right) High
magnification of a bladder
biopsy shows collections of
calcified Schistosoma eggs
associated with giant cell
ranulomatous reaction
in the submucosa in a case of
chronic infection.
SCHISTOSOMIASIS
Microscopic Features
(Left) Medium magnification
of this liver section shows
eriovular granuloma
formation against ova
lodged in veins branching off
from a medium-sized portal
trunk, as well as periportal
fibrosis ("pipestem fibrosis")
with arterial dilation ,
consistent with advanced
hepatic schistosomiasis.
(Right) High magnification of
a liver section shows masses
of Schistosoma eggs ,
some calcified, associated
with subcapsular fibrosis and
inflammation.
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Microscopic Features
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Helminthic Parasitic Infections: Trematodes
SCHISTOSOMIASIS
(Left) Low magnification
of this lung section shows
exuberant eosinophilic
ranulomatous inflammation.
Follow-up high magnification
revealed S. mansoni
eggs. No adult worms
were identified in the
blood vessels. (Right)
Low magnification of this
endometrial biopsy reveals
ranulomatous endometritis.
Differentials include
tuberculosis, schistosomiasis,
coccidioidomycosis,
cytomegalovirus infection,
sarcoidosis, and prior
endometrial ablation.
(Left) Low magnification of
this omental mass (H&E)
shows a pseudotumor
consisting of foamy
histiocytes and inflammatory
cells in whorled masses
around Schistosoma mansoni
eggs . A lateral spike is
seen on 1 of the eggs ,
which is being enveloped
by a giant cell . (Right)
Medium magnification
of this bladder section
reveals 2 Schistosoma
eggs associated with
ranulomatous reaction
with central necrosis,
eosinophils, and chronic
inflammation.
(Left) Medium magnification
of this bladder section
(H&E) shows multiple
ranulomata associated with
chronic and eosinophilic
inflammation. Follow-up
serial sections confirm the
helminth form to be a
Schistosoma egg. (Right)
High magnification of a ceca
olyp (H&E) shows dense
eosinophilic infiltrate and
a subtle helminth fragment
. The morphology
and tissue reaction favor
strongyloidiasis, but
schistosomiasis cannot be
excluded. Correlation with
serologic studies is needed.
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