Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
This page intentionally left blank
SECTION 1
Morphological Diagnosis
of Bacterial Infections
Anaplasmosis and Ehrlichiosis II-1-2
Pertussis II-1-6
Malakoplakia II-1-8
Actinomycosis II-1-10
Botryomycosis II-1-12
Helicobacteriosis II-1-14
Leprosy II-1-16
Nocardiosis II-1-20
Spirochetosis II-1-24
Whipple Disease II-1-26
ANAPLASMOSIS AND EHRLICHIOSIS
Giemsa-stained peripheral blood shows morulae in a
neutrophil, consistent with Anaplasma. Ehrlichia ewingii
is in the differential, and geography, serology, and PCR
can distinguish.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Abbreviations
Human granulocytic anaplasmosis (HGA)
Human granulocytic ehrlichiosis (HGE)
Human monocytic ehrlichiosis (HME)
Human ewingii ehrlichiosis (HEE)
Definitions
Anaplasma (Greek) "without plasma"
phagocytophilum (Greek) "loving phagocytes"
Ehrlichia (German) after Paul Ehrlich
chaffeensis after Fort Chaffee (1st patient identified)
ewingii after Sidney A. Ewing (pioneer of agent)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Anaplasma phagocytophilum
Described in early 1990s as a form of human
monocytic ehrlichiosis distinguished by inclusion
bodies in granulocytes rather than monocytes,
hence termed human granulocytic ehrlichiosis
Formerly known as Ehrlichia equi, later changed to
Ehrlichia phagocytophilum, then was taxonomically
reclassified in 2001 under genus Anaplasma
Transmitted by bites from the black-legged tick
(Ixodes scapularis) in northeast and upper midwest,
and the western black-legged tick (Ixodes pacificus) in
northern California
Reservoirs are deer, elk, and wild rodents
Have been reportedly associated with packed red
blood cell transfusions
Ehrlichia chaffeensis
Primary vector is Amblyomma americanum, less
commonly Ixodes, Dermacentor
II
Reservoirs are white-tailed deer, less commonly
coyotes, goats
1
The presence of morulae (Latin for mulberry) in
circulating monocytes or granulocytes is diagnostic of
ehrlichiosis or anaplasmosis in the appropriate clinical
setting. (Courtesy S. Kroft, MD.)
Ehrlichia ewingii
Mainly canine, reported to infect humans as well
Ehrlichia muris
Primary vector is Ixodes persulcatus complex
Ehrlichia muris-like organism
Suspected vector is Ixodes scapularis
Reports with blood transfusions, organ transplant
CLINICAL ISSUES
Epidemiology
Incidence
Anaplasma
6.1 cases per million in 2010 in USA
5-10% of healthy people in high-prevalence
areas have elevated antibody titers due to prior
exposure
Ehrlichia
2.5 cases per million of E. chaffeensis in 2010 in
USA
Geographical distribution
Anaplasma
90% of USA cases reported in New York,
Connecticut, New Jersey, Rhode Island,
Minnesota, and Wisconsin
Also reported in Central Europe and Scandinavia
Ehrlichia
E. chaffeensis most common; endemic in
southeast, south central, and mid Atlantic USA;
also in Mexico, Central and South America, East
Asia, Europe, and Central Africa
E. ewingii in south central and southeast USA
E. muris in Eastern Europe and Asia
E. muris-like organism in Wisconsin and
Minnesota
Seasonality
Anaplasma
Summer months (June/July) corresponding to
increased numbers of nymphal ticks
2
ANAPLASMOSIS AND EHRLICHIOSIS
Etiology
Anaplasma phagocytophilum: Transmitted by bites
from black-legged tick (Ixodes scapularis) in northeast
and upper midwest, and western black-legged tick
(Ixodes pacificus) in northern California
Ehrlichia chaffeensis: Primary vector is Amblyomma
americanum, less commonly Ixodes, Dermacentor
Clinical Issues
Anaplasma: 90% of USA cases reported in New York,
Connecticut, New Jersey, Rhode Island, Minnesota,
and Wisconsin
E. chaffeensis most common, endemic in southeast,
south central, and mid Atlantic USA; also in Mexico,
Central and South America, East Asia, Europe, and
Central Africa
E. ewingii in south central and southeast USA
Key Facts
Microscopic Pathology
Morulae (microcolonies of Anaplasma within
neutrophils), seen by direct exam stained with eosinazure-type dyes, are present in 20-80% of patients
within 1st week of illness
Morulae (microcolonies of Ehrlichiosis within
mononuclear cells) seen by manual exam of
peripheral blood smear stained with eosin-azure-type
dyes in 1-20% of patients
Ancillary Tests
PCR
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Anaplasma: Sensitivity: 60-70% within 1 week of
illness, decreased by doxycycline treatment
Ehrlichia: 52-87% sensitivity, which may decrease
with doxycycline therapy
Ehrlichia
Mostly May-August
Presentation
Anaplasma
Symptoms begin 1-2 weeks after painless tick bite
and include fever, headache, muscle pain, malaise,
chills, nausea, abdominal pain, cough, confusion
Rare (10% of patients) maculopapular petechiae
rash
Ehrlichia
Usually acute with spectrum of symptoms including
malaise, headache, chills/fever, GI symptoms,
mental status changes, stiff neck, clonus
Macular, maculopapular, or petechial rash present in
36% with HME compared to 10% with HGA
Laboratory Tests
Associated with thrombocytopenia, leukopenia, and
transaminitis
Anaplasma: Neutropenia
Ehrlichia: Hyponatremia
Treatment
Drugs
Doxycycline is first-line treatment
Prognosis
Anaplasma
Severity ranges from asymptomatic to fatal (< 1%)
with complications
Renal failure
Acute respiratory distress syndrome
Toxic shock-like syndrome
Hemophagocytosis
Rhabdomyolysis
Pancreatitis
Can be complicated by opportunistic infections such
as herpes simplex esophagitis, invasive aspergillosis,
and candidiasis
Severity increases in immunosuppression, with HIV,
or nonfunctional spleen
Ehrlichia
Severity ranges from asymptomatic to fatal (2-5%)
with complications
Renal failure
Acute respiratory distress syndrome
Coagulopathy
Myocarditis
Encephalopathy
Severity increased in immunosuppression or with
HIV infection
MICROBIOLOGY
Organism
Small obligate intracellular bacteria
Anaplasma: 0.2-1 m
Ehrlichia: 0.2-2 m
Specialized systems involving human promyelocytic
leukemia cells required for culture
MICROSCOPIC PATHOLOGY
Peripheral Blood Smear
Anaplasma: Morulae (microcolonies within
neutrophils), seen by direct exam stained with eosinazure-type dyes, are present in 20-80% of patients
within 1st week of illness
E. ewingii shows similar appearance but has different
geographic distribution
Ehrlichia: Morulae (microcolonies within mononuclear
cells) seen by manual exam of peripheral blood
smear stained with eosin-azure-type dyes in 1-20% of
patients
Ehrlichia may also show atypical lymphocytes with
large, hyperchromatic nuclei, abundant basophilic
cytoplasm, and prominent cytoplasmic granules
II
1
3
ANAPLASMOSIS AND EHRLICHIOSIS
ANCILLARY TESTS
PCR
Anaplasma
Sensitivity: 60-70% within 1 week of illness,
decreased by doxycycline treatment
Ehrlichia
52-87% sensitivity, which may decrease with
doxycycline therapy
May not detect E. muris-like organisms species from
Wisconsin and Minnesota
Serologic Testing
Anaplasma
Antibody titers detected 7-10 days of illness with
IgM elevated for months to years
Gold standard serologic test is indirect
immunofluorescence assay (IFA) on paired serum
samples to demonstrate 4x rise in IgG titers in first 4
weeks
90-95% sensitive if performed with acute or
convalescent serology after 3-4 weeks
Ehrlichia
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Antibodies detectable in 2-3 weeks and may persist
Current case definition is 4x change in IFA titre
between acute and convalescent stages
IFA is 94-100% sensitive if a 2nd paired sample 14
days post onset of symptoms
Some cross reactivity between E. chaffeensis and A.
phagocytophilum and E. ewingii
DIFFERENTIAL DIAGNOSIS
Rocky Mountain Spotted Fever (Rickettsia
rickettsii)
Because Amblyomma and Dermacentor ticks can also
transmit Rickettsia, mixed infections can occur
Anaplasma/Ehrlichia less commonly have rash (< 40%)
Babesiosis (Babesia microti)
Because Ixodes species ticks also transmit various
Babesia species, mixed infections are known to occur
Babesia infects red blood cells with diagnostic pearshaped and cross forms
Lyme (Borrelia burgdorferi)
Because Ixodes species ticks also transmit B. burgdorferi,
mixed infections are known to occur
Erythema migrans (bull’s-eye rash) should warrant
investigation for Lyme
Heartland Virus Infection
Clinical signs/symptoms similar to Ehrlichiosis with
tick exposure (Missouri and Tennessee)
Patients fail to respond to doxycycline but there is no
current clinical test or therapy available
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Morulae seen by manual examination of peripheral
smear in 20-80% of patients with anaplasmosis
compared to 1-20% of patients with ehrlichiosis
Pathologic Interpretation Pearls
Look for signs of mixed infections on peripheral
smear, such as intraerythrocytic rings and "Maltese
cross," suggestive of Babesia
Geographic location of patient is helpful, but
confirmation by PCR or serology is diagnostic
SELECTED REFERENCES
1. Jahfari S et al: Circulation of four Anaplasma
phagocytophilum ecotypes in Europe. Parasit Vectors.
7:365, 2014
2. Rand JV et al: Intracytoplasmic granulocytic morulae
counts on confirmed cases of ehrlichiosis/anaplasmosis in
the Northeast. Am J Clin Pathol. 141(5):683-6, 2014
3. Sachdev SH et al: Severe life-threatening Ehrlichia
chaffeensis infections transmitted through solid organ
transplantation. Transpl Infect Dis. 16(1):119-24, 2014
4. Schotthoefer AM et al: A clinical, diagnostic, and ecologic
perspective on human anaplasmosis in the Upper Midwest.
WMJ. 113(3):107-14; quiz 115, 2014
5. Regan J et al: A confirmed Ehrlichia ewingii infection likely
acquired through platelet transfusion. Clin Infect Dis.
56(12):e105-107, 2013
6. Annen K et al: Two cases of transfusion-transmitted
Anaplasma phagocytophilum. Am J Clin Pathol.
137(4):562-5, 2012
7. Pritt BS et al: Emergence of a new pathogenic Ehrlichia
species, Wisconsin and Minnesota, 2009. N Engl J Med.
365(5):422-9, 2011
8. Yabsley MJ: Natural history of Ehrlichia chaffeensis:
vertebrate hosts and tick vectors from the United States
and evidence for endemic transmission in other countries.
Vet Parasitol. 167(2-4):136-48, 2010
9. Centers for Disease Control and Prevention (CDC):
Anaplasmosis and ehrlichiosis - Maine, 2008. MMWR Morb
Mortal Wkly Rep. 58(37):1033-6, 2009
10. Bakken JS et al: Human granulocytic anaplasmosis. Infect
Dis Clin North Am. 22(3):433-48, viii, 2008
11. Dumler JS et al: Ehrlichioses in humans: epidemiology,
clinical presentation, diagnosis, and treatment. Clin Infect
Dis. 45 Suppl 1:S45-51, 2007
12. Dumler JS et al: Human granulocytic anaplasmosis
and Anaplasma phagocytophilum. Emerg Infect Dis.
11(12):1828-34, 2005
13. Hamilton KS et al: Characteristic peripheral blood findings
in human ehrlichiosis. Mod Pathol. 17(5):512-7, 2004
14. Stone JH et al: Human monocytic ehrlichiosis. JAMA.
292(18):2263-70, 2004
15. Nadelman RB et al: Simultaneous human granulocytic
ehrlichiosis and Lyme borreliosis. N Engl J Med.
337(1):27-30, 1997
II
1
4
Microscopic Features
A
A
g
A
g
A
A
A
g
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
ANAPLASMOSIS AND EHRLICHIOSIS
(Left) A smaller inclusion
consistent with the
intracellular bacteria,
naplasma, is shown .
Note the hyposegmented
and band-form neutrophils
without toxic granulations.
(Courtesy T. Wieczorek,
MD, PhD.) (Right)
Inclusions consistent with
the intracellular bacteria,
naplasma, are shown
. Note the 3- to 4-lobed
neutrophils and toxic
ranulations. Large numbers
of toxic granulations (as in
sepsis) may be confused
with the bacteria. (Courtesy
T. Wieczorek, MD, PhD.)
(Left) A large inclusion
consistent with the
intracellular bacteria
Ehrlichia is shown . Note
the monocyte containing
the organism, which is
typical of HME. (Right)
Inclusion consistent with
naplasma is shown .
Note the hyposegmented
neutrophils and lack of toxic
ranulations. A monocyte
is shown for comparison.
lthough mixed infections
with other agents are
common, Anaplasma and
Ehrlichia are not commonly
coexisting. (Courtesy Dr. T.
Wieczorek.)
(Left) A large inclusion
consistent with the
intracellular bacteria
naplasma is shown .
Note the hyposegmented
neutrophil containing the
organism, which is typical
of HGE. (Courtesy Dr. T.
Wieczorek.) (Right) An
inclusion consistent with
naplasma is shown .
Note the hyposegmented
neutrophil with toxic
ranulations. Large
aggregates of giant platelets
can be seen, and
overlapping platelets on
leukocytes can be confusing.
(Courtesy Dr. T. Wieczorek.)
II
1
5
PERTUSSIS
A small airway from an infant who died of pertussis
shows clumps of bacteria lining the ciliated respirator y
epithelium at autopsy.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Synonyms
Bordetella pertussis Infection
Whooping cough, 100 days cough
Definitions
From Jules Bordet (Belgian bacteriologist)
Latin: "Per" (away, extreme) + "tussis" (cough)
ETIOLOGY/PATHOGENESIS
Infectious Agents
B. pertussis
Gram-negative, encapsulated, nonmotile, aerobic
bacillus
Humans are only known host
Spread by respiratory droplets with a 1- to 2-week
incubation period
Upon entry into respiratory tract, bacteria bind to
cilia via filamentous hemagglutinin adhesin
Tracheal cytotoxins inhibit movement of cilia,
decreasing clearance of mucus, which leads to
extreme cough
Bacteria further inhibit phagocytosis through
pertussis toxin, which disrupts phagocyte adenylate
cyclase production of cyclic AMP
Lymphocytes fail to migrate to lymph nodes
(resulting in lymphocytosis)
Bordetella parapertussis and Bordetella holmesii
May cause pertussis-like illness
Causes other nonpertussis illness symptoms
Bordetella pertussis are gram-negative coccobacilli,
which can be highlighted with Giemsa stain and silver
stains to demonstrate the adherence to epithelium.
Presentation
Rhinorrhea, cough, fever
Progresses to violent coughing with inspiratory
"whoop"
Damage and loss of epithelium can lead to sepsis
Laboratory Tests
Lymphocytosis (lymphocyte count over 4,000 cells/uL
(adults) or 8,000 cells/uL (pediatric)
Lymphocytes may show characteristic clefting on
peripheral blood smear
CSF may show elevated protein
Diagnosis primarily by culture from nasopharyngeal or
oropharyngeal swab
ELISA test for antibodies (IgG, IgA, or IgM) to
filamentous hemagglutinin adhesin (FHA) or pertussis
toxin (PT)
Treatment
Vaccination is mainstay of disease prevention
Antibiotics may shorten duration of illness
Prognosis
Mortality is 1.2% (primarily occurs in unvaccinated
children)
MICROBIOLOGY
Culture
Growth on Bordet-Gengou agar or buffered charcoal
yeast extract (BCYE) agar with selective antibiotic
(cephalosporin)
II
1
6
CLINICAL ISSUES
Epidemiology
Affects 15-40 million people worldwide with
200,000-300,000 deaths annually
MACROSCOPIC FEATURES
Patterns of Infection Found in Fatal Cases
Otitis media, laryngitis, tracheitis, bronchitis,
pneumonia
Etiology
Bordetella pertussis: Gram-negative, encapsulated,
nonmotile, aerobic bacillus
Humans are the only known host
Clinical Issues
Affects ~ 40 million people worldwide with ~ 300,000
deaths annually
Progresses to violent coughing with inspiratory
"whoop"
PERTUSSIS
Key Facts
Damage and loss of epithelium can lead to sepsis
Lymphocytosis (lymphocyte count > 4,000 cells/uL
(adults) or 8,000 cells/uL (pediatric)
Microscopic Pathology
Respiratory epithelium is coated with bacteria
Neutrophils within walls of trachea/bronchi are seen
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
MICROSCOPIC PATHOLOGY
Histologic Features
Necrotizing bronchiolitis, intraalveolar hemorrhage,
and fibrinous edema
Respiratory epithelium is coated with bacteria
Epithelium may be denuded with secondary
infection
Neutrophils within walls of trachea/bronchi are seen
Bronchopneumonia with extension into alveolar
spaces with secondary infection
Interstitial pneumonia as a complication of progressive
disease
Bronchiolitis obliterans organizing pneumonia as a
complication of progressive disease
Diffuse alveolar damage may be end result of fatal
infection
ANCILLARY TESTS
Histochemistry
Innumerable gram-negative organisms are best
visualized with silver stains or Giemsa stains
Immunohistochemistry
Available in reference labs (CDC) for confirming
diagnosis
May show intracellular bacteria and bacteria antigens
within phagocytic cells and respiratory epithelium
PCR
Directed PCR for insertional sequences specific for B.
pertussis, B. parapertussis, &/or B. holmesii
DIFFERENTIAL DIAGNOSIS
Adenovirus and Other Viral Infections
Similar appearance but with viral cytopathic effect,
negative special stains for bacteria
Diphtheria
Nonvaccinated patient with trachea pseudomembrane,
mostly upper airway but may have secondary
pneumonia
SELECTED REFERENCES
1. Arbefeville S et al: Development of a multiplex realtime PCR assay for the detection of Bordetella pertussis
and Bordetella parapertussis in a single tube reaction. J
Microbiol Methods. 97:15-9, 2014
2. Barlow RS et al: Vaccinated children and adolescents
with pertussis infections experience reduced illness
severity and duration, Oregon, 2010-2012. Clin Infect Dis.
58(11):1523-9, 2014
3. Cherry JD et al: The respiratory pathology in infants with
sudden unexpected deaths in whom respiratory specimens
were initially PCR-positive or PCR-negative for Bordetella
pertussis. Infection. 39(6):545-8, 2011
4. Paddock CD et al: Pathology and pathogenesis of fatal
Bordetella pertussis infection in infants. Clin Infect Dis.
47(3):328-38, 2008
MICROSCOPIC FEATURES
(Left) In this section of trachea from a fatal pertussis infection, the normal ciliated epithelium is interrupted by blue/gray clumps of bacteria
on the surface. (Center) Giemsa stain highlights the bacterial forms
adjacent alveolar spaces
demonstrate innumerable bacteria in clouds as part of a secondary bacterial infection in fatal pertussis.
in pertussis to confirm the diagnosis. (Right) A small airway and the
II
1
7
MALAKOPLAKIA
Malakoplakia is characterized by sheets of histiocytes
with eccentric, bland nuclei and brightly eosinophilic
granular cytoplasmic (a.k.a. von Hansemann) cells.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Definitions
Malakoplakia: From Greek ("soft plaques")
ETIOLOGY/PATHOGENESIS
Acquired/Infectious
Defective intracytoplasmic digestion of bacteria
in phagolysosomes in setting of chronic/indolent
infections
Escherichia coli, Proteus, Klebsiella, Staphylococcus
aureus, Mycobacterium, Rhodococcus equi
Cellular and extracellular accumulation of partially
digested bacteria become trapped in lysosomal
components
CLINICAL ISSUES
Epidemiology
Age
Adults; peak incidence in 5th decade
Gender
More common in females
Patient populations
More prevalent in immunocompromised
populations
HIV/AIDS
Post transplant
Inherited immune disorders
Chronic steroid use
Chronic alcohol abuse
Uncontrolled diabetes
Site
II
Urinary tract: Most frequently involved organ system
Associated with chronic coliform cystitis
Bladder more common than ureters and kidneys
1
Intracytoplasmic inclusions known as Michaelis-Guttman
bodies are pathognomonic for malakoplakia. They are
smaller than the nuclei of von Hanseman cells, round/
targetoid, and basophilic.
Other
Gastrointestinal tract, lungs, thyroid, prostate,
testes, skin
Presentation
Urinary tract lesions
Urinary bladder
Frequency, urgency, dysuria, hematuria
Ureters
Obstructive renal failure
Kidneys
Hematuria, proteinuria
Gastrointestinal tract
May be clinically silent
Diarrhea, obstruction, pain
Skin
Subcutaneous nodule with sinus tract formation
Treatment
Surgical approaches
Ideal for localized/unilateral disease
Best curative therapy
Drugs
Antibiotics
Vitamin C
Bethemacol
Prognosis
Varies by site, extent, associated disease conditions
and therapeutic options
MACROSCOPIC FEATURES
Gross Features
Yellow-brown soft plaques and nodules
Umbilicated centers
8
MALAKOPLAKIA
Etiology
Defective digestion of bacteria in phagolysosomes
Clinical Issues
More prevalent in females and immunocompromised
populations
Most frequent site of involvement: Urinary tract,
especially bladder
Key Facts
Macroscopic Pathology
Yellow-brown, soft plaques and nodules with
umbilicated centers
Microscopic Pathology
Sheets of von Hansemann cells
Michaelis-Gutmann bodies
Acute and chronic inflammation
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
MICROSCOPIC PATHOLOGY
Histologic Features
Sheets of von Hansemann cells
Histiocytes with eccentric nuclei and brightly
eosinophilic cytoplasm
Stain positive on periodic acid-Schiff
Michaelis-Gutmann bodies
Concentric, targetoid or owl’s-eye structures
5-10 microns in diameter (smaller than nuclei of
von Hansemann cells)
Basophilic
Present within von Hanseman cells or in
extracellular spaces
Comprised of mineralized bacterial fragments
trapped in lysosomal components
May not be present in early or late lesions
Stain positive on periodic acid-Schiff, Prussian blue,
and von Kossa stains
Histologic evidence of bacteria may or may not be
present
Inflammation
Lymphocytes, neutrophils, plasma cells
Late lesions may show marked fibrosis
Cytologic Features
von Hansemann cells and Michaelis-Gutmann bodies
ANCILLARY TESTS
Immunohistochemistry
Positive (von Hansemann cells)
CD68, alpha chymotrypsin
Negative (von Hansemann cells)
S100
DIFFERENTIAL DIAGNOSIS
Langerhans Cell Histiocytosis
Cells positive for S100, langerin, and CD1a
Granular Cell Tumor
Cells positive for S100
Infiltrative edge
Xanthogranuloma
Lack Michaelis-Gutman bodies
SELECTED REFERENCES
1. Afonso JP et al: Cutaneous malakoplakia: case report and
review. An Bras Dermatol. 88(3):432-7, 2013
2. Garg M et al: Malakoplakia presenting as an enlarging neck
mass: Case presentation and review of the literature. Head
Neck. 32(9):1269-72, 2010
3. Yousef GM et al: Malakoplakia outside the urinary tract.
Arch Pathol Lab Med. 2007 Feb;131(2):297-300. Review.
Erratum in: Arch Pathol Lab Med. 133(6):850, 2009
IMAGE GALLERY
(Left) In some cases of malakoplakia, like this lesion involving prostate, there is a mixed inflammatory infiltrate and Michaelis-Gutmann bodies
are rare . (Center) Mineralized calcium within Michaelis-Gutmann bodies is highlighted by a von Kossa stain. (Right) Periodic acid-Schiff stain
of renal malakoplakia highlights the granular cytoplasm of macrophages known as von Hanseman cells and intensely stains the characteristic
Michaelis-Gutmann bodies .
II
1
9