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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
ACTINOMYCOSIS
Actinomyces form sulfur granules, as seen in this tonsil.
sulfur granules are clumps of bacterial forms with a
basophilic center and eosinophilic periphery.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Synonyms
Actinomyces
Lumpy jaw
ETIOLOGY/PATHOGENESIS
Infectious Agents
Actinomyces israeli is the most frequently encountered
pathogenic species (invasive with tissue penetration/
breakdown)
Actinomyces viscosus and Actinomyces meyeri are
less common pathogenic species (more likely
disseminated)
Risk Factors
Men affected 3x more often than women
Poor oral hygiene with recent decline in incidence
attributed to improved oral hygiene
Chronic steroid use, leukemia, HIV, status post organ
transplantation
Bisphosphonate use (osteonecrosis)
Alcohol abuse
Breach of tissue integrity
Prolonged use of intrauterine devices (IUD) (> 2 years)
Diabetes
CLINICAL ISSUES
Presentation
Actinomyces species are frequently seen as incidental
bacteria on biopsies or part of mixed flora colonizing
lesions
Infection is clinically classified by site of infection
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Orocervicofacial
Most common site of infection
Actinomyces are gram-positive (sometimes gramvariable) filamentous rods, which usually appear in
clumps or clusters as granules or singly as invasive
bacterial infections.
Presents with fever, pain, and localized swelling
that may be mistaken for neoplastic process
Thoracic
2nd most common site of infection
Usually presents as pneumonia: Low-grade fever,
cough, and shortness of breath, sometimes with
notable weight loss and hemoptysis
Abdominopelvic
Usually related to ruptured appendix
Cases related to prolonged IUD use may present
with fever, vaginal discharge, pain, or weight loss,
or may be an incidental finding on biopsy
Treatment
Surgical debridement (with extensive necrosis) or sinus
tract excision (chronic)
Penicillin is first-line antibiotic therapy
Removal of IUD (in IUD-related cases)
IMAGE FINDINGS
General Features
Findings are nonspecific
May mimic any localized infection or neoplastic
process
Lymphadenopathy is rarely seen
MICROBIOLOGY
Culture
Anaerobic to microaerophilic commensals of
oropharynx, gastrointestinal tract, and genitourinary
tract
Growth on enriched media (serum or blood) in
anaerobic conditions produces colonies in 2-4 days
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ACTINOMYCOSIS
Etiology
Actinomyces israeli is most frequently encountered
pathogenic species
Chronic steroid use, leukemia, HIV, status post organ
transplantation
Prolonged use of intrauterine devices (> 2 years)
Clinical Issues
Orocervicofacial most common site of infection
Key Facts
Thoracic site usually related to aspiration of
oropharyngeal secretions
Microscopic Pathology
Filamentous bacterial forms
Sulfur granules
Ancillary Tests
Positive on Gram stain and GMS or MSS silver stains
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
MACROSCOPIC FEATURES
General Features
Tissue necrosis sinus tract formation
MICROSCOPIC PATHOLOGY
Histologic Features
Filamentous bacterial forms
Sulfur granules
Clumped colonies (often multiple) of organisms
with round to ovoid shape
Basophilic center with eosinophilic periphery
(Splendore-Hoeppli phenomenon)
Comprised of swollen terminal processes or
"clubs" and proteinaceous debris
Tissue necrosis
Sinus tract formation
Variably present and seen in orocervicopharyngeal
cases
ANCILLARY TESTS
Special Stains
Positive on Gram stain and GMS or MSS silver stains
DIFFERENTIAL DIAGNOSIS
Pseudoactinomycotic Radiate Granules
(PAMRAGs) in IUD Use
May be found in endometrial biopsies and curettings
Eumycetoma
Fungal mycetomas may appear very similar to
actinomycetomas in tissue with presence of hyphae
and culture correlation distinguishing
Botryomycosis
May similarly form colonies mimicking sulfur granules
Nocardiosis
Gram-positive filamentous bacteria that may also form
granules
Variably positive for acid-fast stains (modified acid-fast
or Kinyoun stain)
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Bacterial culture is gold standard for definitive
diagnosis of actinomycosis
SELECTED REFERENCES
1. Valour F et al: Actinomycosis: etiology, clinical features,
diagnosis, treatment, and management. Infect Drug Resist.
7:183-97, 2014
IMAGE GALLERY
(Left) Actinomyces stains positive with silver stains and includes a differential diagnosis of thin hyphal of fungi as well as nocardiosis. (Center)
Gram stain highlights the filamentous bacterial forms that can be obscured in H&E stained sections. (Right) Pseudoactinicomycotic radiate
granules (PAMRAGs) are common in endometrial biopsies and are associated with intrauterine device use. Unlike sulfur granules, PAMRAGs are
refractile and bacterial forms are not present.
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BOTRYOMYCOSIS
H&E stain shows abscess formation containing numerous
granules centered among neutrophils.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Synonyms
Pyoderma vegetans, bacterial pseudomycosis
Definitions
"Botrys" is a Latin term for "bunch of grapes"
ETIOLOGY/PATHOGENESIS
Unusual Host Response to Several
Nonfilamentous Bacteria
Culture-proven lesions are often due to Staphylococcus
aureus (gram-positive cocci)
Gram-negative organisms such as Proteus spp,
Escherichia coli, and Pseudomonas aeruginosa among
others have been reported
Histological diagnosis requires presence of
nonfilamentous bacteria seen on tissue Gram stain
("granules")
A granule is comprised of etiological agent in
"matrix"
This matrix thought to be antigen-antibody
complexes (Splendore-Hoeppli phenomenon)
In severe immunosuppressed patients, Splendore-
Hoeppli phenomenon may be absent
Exact pathogenesis remains unknown
CLINICAL ISSUES
Presentation
More common among immunocompromised patients
and it involves skin &/or viscera
In cutaneous disease, patients present with mass
or plaques, abscesses, and ulcers, which can mimic
II
mycetoma or other fungal causes (eumycetoma)
1
Gram stain shows the outer zone of the granulomatous
inflammation . The botryomycosis "granule" contains
a compact mass of basophilic cocci embedded in an
eosinophilic matrix .
Visceral disease can be primary (e.g., lung, liver, vulva,
heart, etc.) and can mimic carcinoma
Visceral diseases can be secondary when infection
spreads to internal organs from a cutaneous lesion
Treatment
Long-term antibiotic and surgical debridement
Prognosis
Cutaneous botryomycosis usually responds better than
visceral to antibiotic therapy
Successful treatment depends on site of lesion and
immune status of host
MICROBIOLOGY
Bacterial Culture
Gold standard test to isolate strain and to identify and
perform susceptibility testing
Aerobic and anaerobic should be considered
MACROSCOPIC FEATURES
General Features
Draining sinuses may show granules
Cut sections may show deep-seated granules
MICROSCOPIC PATHOLOGY
Histologic Features
Abscess contains numerous granules
Granules contain causative bacteria (either grampositive or gram-negative)
Can cause granulomatous reaction
Cytologic Features
Granules may demonstrate bacterial forms at edges if
smeared
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Clinical Issues
More common among immunocompromised
patients
Can involve skin and viscera
Microscopic Pathology
Abscess contains numerous granules
Granules contains causative bacteria (gram-positive
or gram-negative)
Granulomatous inflammation
BOTRYOMYCOSIS
Key Facts
Ancillary Tests
Gram stain to determine if it is a gram-positive or
gram-negative agent
Top Differential Diagnoses
Mycetoma, TB, and sporotrichosis
Can be confused with invasive carcinoma ( visceral
disease)
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
ANCILLARY TESTS
Histochemistry
Gram stain to determine if it is a gram-positive or
gram-negative agent
PAS stain to stain granule
DIFFERENTIAL DIAGNOSIS
Mycetoma
Uncommon chronic infectious disease of skin and
subcutaneous tissues in tropical countries
Characterized by suppurative granulomas, draining
sinuses, and presence of colonial "grains" in exudates
Caused by traumatic inoculation of either
Actinomycetes (bacterial) or a fungus (eumycetoma)
Tuberculosis
AFB-positive staining of organisms
Granulomatous reaction more common
Other Fungal Infections
Sporotrichosis: Spread along lymphatics
Cysts
Epidermal cysts communication and contain keratin
or fluid
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Inflammation, ulceration, suppuration with numerous
granules and frequent giant cells
Granules are basophilic on H&E stain
Gram stain to detect bacteria
GMS to exclude a fungal cause
SELECTED REFERENCES
1. Gupta K et al: Cardiac botryomycosis: an autopsy report. J
Clin Pathol. 61(8):972-4, 2008
2. Leong YL et al: Primary pulmonary botryomycosis with
multiple adjacent organ involvement mimicking mucosaassociated lymphoid tissue lymphoma. J Formos Med
Assoc. 104(10):744-7, 2005
3. Machado CR et al: Botryomycosis. Dermatology.
211(3):303-4, 2005
4. de Vries HJ et al: Botryomycosis in an HIV-positive subject.
J Eur Acad Dermatol Venereol. 17(1):87-90, 2003
5. Bersoff-Matcha SJ et al: Primary pulmonary botryomycosis:
case report and review. Clin Infect Dis. 26(3):620-4, 1998
6. Schlossberg D et al: The Splendore-Hoeppli phenomenon
in hepatic botryomycosis. J Clin Pathol. 51(5):399-400,
1998
7. Bonifaz A et al: Botryomycosis. Int J Dermatol. 35(6):381-8,
1996
Carcinoma
Visceral disease may mimic carcinoma (and vice versa)
IMAGE GALLERY
(Left) H&E section shows extensive neutrophilic infiltrate and abscess-like formation around the granules. (Center) H&E section reveals
a granule containing small cocci and surrounded by eosinophilic matrix (Splendore-Hoeppli material)
botryomycosis infection with extensive granule formation and abscess formation can resemble the myocytoma grains
. (Right) High-power view of
.
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HELICOBACTERIOSIS
Stomach biopsy with a lymphoid aggregate (strongly
suggestive of Helicobacter pylori infections in Western
populations) is shown. Lymphoid aggregates are more
common in developing countries.
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Synonyms
Infectious ulcer, gastric ulcer, duodenal ulcer
Helicobacter pylori infection
Definitions
Greek: "Heliks" (twisted or spiral) + "bakterion" (small
staff)
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Worldwide distribution transmitted by fecal-oral or
oral-oral transmission
Infectious Agents
Helicobacter pylori (formerly Campylobacter pylori)
infection
Accounts for 99% of helicobacteriosis
Risk of ulcer with exposure: 20%
Risk of cancer: < 5%
Helicobacter heilmannii
1% of all Helicobacter infections
CLINICAL ISSUES
Epidemiology
Upper gastrointestinal tract colonization/infection in
50% of world population
Presentation
Asymptomatic (80%)
Nausea, vomiting, abdominal pain
"Heartburn," halitosis, morning hunger
Diarrhea
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Gastric ulcer: Worsens with food due to increased acid
production
1
High-power view of an crypt containing H. pylori is
shown with numerous, faintly staining organisms all
along the epithelial border. Special stains or IHC can
confirm the diagnosis.
Gastric adenocarcinoma: Complication of chronic
untreated infection with ulceration (early satiety,
hematochezia)
Gastric lymphoma: Complication of chronic
inflammation due to infection
Duodenal ulcer: Improves with food due to closing of
pylorus
Usually associated with predominantly antral
gastritis
Laboratory Tests
Serum antibody test
Exposure to bacteria, least sensitive for presence of
bacteria
Sensitivity and specificity > 90% (new infection)
Stool antigen test
Presence of bacteria, does not indicate degree of
disease, can determine eradication
Sensitivity and specificity are 98% and 94% (initial
stage of disease)
Breath urease/urea test
Detects active production of urease enzyme (which
bacteria uses to neutralize stomach acid)
Highly sensitive and specific
Treatment
Triple regiment of antibiotics and antacid medications
are used to heal ulcer and eradicate organism
e.g., omeprazole (or lansoprazole), amoxicillin,
clarithromycin; bismuth subsalicylate,
metronidazole, and tetracycline
Prognosis
In patients where infection is eradicated, risk of cancer
is reduced
Reinfection may occur
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HELICOBACTERIOSIS
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Etiology
Worldwide, fecal-oral or oral-oral transmission
Helicobacter pylori
Accounts for 99% of helicobacteriosis
Risk of ulcer with exposure: 20%; risk of cancer: <
5%
Clinical Issues
Breath urease/urea test
MICROBIOLOGY
Characteristics
Gram-negative, microaerophilic curved bacterium
with flagella
Produces urease for protection from stomach acid
Culture
Indicated if patient fails basic triple regimen therapy
for eradication of organism (drug resistance)
MICROSCOPIC PATHOLOGY
Histologic Features
H. pylori on biopsy
Small, faint collections of long, curved rods at
epithelia cell border (within upper quarter of cell) or
collections in lumen
Chronic gastritis
Increased plasma cells in lamina propria
Lymphoid aggregates in mucosa
Atrophic gastritis
Loss of mucosal epithelial cells, glandular
metaplasia, fibrosis
Mucinous intestinal type gland metaplasia dysplasia
Gastric adenocarcinoma
Mucosa-associated lymphatic tissue (MALT)
lymphoma
Key Facts
Microscopic Pathology
H. pylori on biopsy
Chronic gastritis: Lymphoid aggregates in mucosa
ANCILLARY TESTS
Histochemistry
Organisms seen on Gram stain (negative), Giemsa
stain (faint), Warthin-Starry silver stain (black),
Alcian yellow (blue-green), Wright-Giemsa (blue), and
Toluidine blue (dark blue)
Immunohistochemistry
Anti-H. pylori antibodies are more sensitive and
specific than histochemistry and should be used for
confirmation
DIFFERENTIAL DIAGNOSIS
Autoimmune Gastritis
Limited to body and fundus, atrophy of oxyntic
glands with mucinous metaplasia, hyperplasia of
enterochromaffin-like cells
Absence of Helicobacter on special stains/IHC; history
of autoimmune disease(s)
SELECTED REFERENCES
1. Varbanova M et al: Chronic gastritis - an update. Best Pract
Detects active production of urease enzyme, highly
sensitive and specific
Small, faint collections of long, curved rods at
epithelia cell border (within upper quarter of cell)
or collections in lumen
Both curved rod forms and coccoid forms (after
therapy) are detected by IHC
Res Clin Gastroenterol. 28(6):1031-42, 2014
MICROSCOPIC FEATURES
(Left) Low-power view of H. pylori infection demonstrates chronic inflammation, crypt distortion, and focal epithelium loss. (Center) Giemsa-
stained section of an intestinal biopsy with H. pylori infection demonstrates faintly positive organisms at the epithelial surface. (Right)
Immunohistochemical stain for H. pylori demonstrates organisms lining the epithelium of an infected patient.
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LEPROSY
Lepromatous leprosy (LL) demonstrates diffuse infiltration
with nodules involving the ear lobules and L nodules
involving the face. (Courtesy S. Dogra, MD.)
TERMINOLOGY
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
Synonyms
Hansen disease
Definitions
Middle English: "lepry" (covered with scales, scaly)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Mycobacterium leprae
Gram-positive, acid-fast, obligatory intracellular,
rod-shaped bacillus
Exact mechanism of transmission of leprosy is
unknown
There is no evidence of skin-skin contact producing
infection
Leprosy bacillus spreads to different organs (mainly
skin and nerves) and induces immune reaction
CLINICAL ISSUES
Epidemiology
Affects millions of people worldwide
Endemic mainly in sub-Saharan Africa, Brazil, Indian
subcontinent, and Southeast Asia
Lepromatous leprosy with diffuse infiltration of the
face shows prominent superciliary arches giving rise
to "leonine facies." Madarosis and early saddle nose
deformity is also present. (Courtesy S. Dogra, MD.)
Treatment
Antibiotics include dapsone, rifampicin and
clofazimine
Multidrug therapy is primarily used
Steroids and other anti-inflammatory medications
to relieve nerve swelling and prevent long-term
deformity
Surgery to drain abscesses or correct deformities
Prognosis
Curable with initiation and completion of therapy
Ridley-Jopling Classification
Tuberculoid form: Strong immunity (single or small
lesions, paucibacillary)
Lepromatous form: Limited immunity (diffuse skin
involvement, multibacillary)
Types of Leprosy Reactions
Type I reaction (lepra) where disease can change from
lepromatous form to tuberculoid during therapy
Type II reaction (erythema nodosum) occurs in
borderline lepromatous patients
Immune complex forms very tender lesions or
vasculitis
Type III reaction (lucid phenomenon) only occurs in
lepromatous leprosy and is characterized by diffuse
skin edema ("la belle femme")
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Presentation
Skin
Macules, papules, or nodules
Single or multiple with hypopigmentation
Loss of sensation ( nerve involvement)
Peripheral nerves
Thickened nerve (inflammation) with loss of
sensation
Upper respiratory tract
Eyes
MICROBIOLOGY
Culture
Has not been cultured on artificial media
Foot pads of mice or armadillos (impractical for
routine diagnosis)
Terminology
Chronic infectious disease caused by Mycobacterium
leprae, an acid-fast, obligatory intracellular, rod-
shaped bacillus
Clinical Issues
Affects millions of people worldwide
Endemic mainly in sub-Saharan Africa, Brazil, Indian
subcontinent, and Southeast Asia
Skin
Peripheral nerves
Multidrug therapy is primarily used
Curable with initiation and completion of therapy
Microscopic Pathology
Strongly acid-fast rod-shaped organism
LEPROSY
Key Facts
Lepromatous leprosy: Sheets of macrophages filled
with numerous intracellular organisms
Intracellular and extracellular masses (globi): Clumps
of bacilli (erythema nodosum leprosum)
Tuberculoid leprosy: "Tuberculoid" granulomatous
reaction and extensive infiltration to nerves
throughout dermis
Positive skin smears, but can be negative in
tuberculoid or borderline forms
Ancillary Tests
Modified Ziehl-Neelsen (Wade-Fite) stain
Top Differential Diagnoses
Granulomatous or histiocytic disorders
Fibrous histiocytoma
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
MICROSCOPIC PATHOLOGY
Histologic Features
Strongly acid-fast rod-shaped organism (Wade-Fite
stain)
Lepromatous leprosy (LL) present with sheets of
macrophages with abundant pink to pale cytoplasm
filled with numerous intracellular organisms (globi)
in dermis with no well-formed granulomas or nerve
infiltration
Intracellular and extracellular masses (globi) consist of
clumps of bacilli in nerve, vessels, arrectores pilorum
muscles; or subcutaneous nodules (erythema nodosum
leprosum)
Tuberculoid leprosy (TL) present with "tuberculoid"
granulomatous reaction and extensive infiltration to
nerves throughout dermis
Indeterminate leprosy (IL) usually present with fewer
histocytic infiltrates and fewer organisms
Borderline leprosy (BL) has perineural fibrosis with
onion-skin pattern and circumscribed granulomatous
reaction with lymphocytic response
Lucio phenomenon: Leukocytoclastic vasculitis and
epidermal infarction
Cytologic Features
Positive skin smears, but can be negative in
tuberculoid or borderline forms
ANCILLARY TESTS
Special Stains
Modified Ziehl-Neelsen (Wade-Fite) stain
Organisms may not appear on standard Ziehl-Neelsen
or Kinyoun AFB stains
DIFFERENTIAL DIAGNOSIS
Granulomatous Disorders
TB special stain and clinical history can help in
making accurate diagnosis
Sarcoidosis special stain negative for acid-fast bacilli
Histiocytic Disorders
Fibrous histiocytoma; negative for acid-fast rod-shaped
organisms
Histocytic reaction to foreign materials can mimic
lepromatous leprosy
Lymphoma with histocytic infiltrates might mimic
leprosy
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Foamy histocytes contain thick aggregates of
mycobacteria (lepromatous leprosy)
Lymphocytic infiltrate and granulomatous reaction
(tuberculoid leprosy)
SELECTED REFERENCES
1. Singh A et al: Histopathological features in leprosy,
post-kala-azar dermal leishmaniasis, and cutaneous
leishmaniasis. Indian J Dermatol Venereol Leprol.
79(3):360-6, 2013
2. Grimaud J: [Peripheral nerve damage in patients with
leprosy.] Rev Neurol (Paris). 168(12):967-74, 2012
3. Legendre DP et al: Hansen’s disease (Leprosy): current and
future pharmacotherapy and treatment of disease-related
immunologic reactions. Pharmacotherapy. 32(1):27-37,
2012
4.
Pinquier L; groupe d’histopathologie cutane de Socit
franaise de dermatologie: [Histopathology of leprosy.]
Ann Dermatol Venereol. 138(11):777-81, 2011
5. Piris A et al: Global dermatopathology: Hansen’s disease-current concepts and challenges. J Cutan Pathol. 37 Suppl
1:125-36, 2010
6. Cuevas J et al: Erythema nodosum leprosum: reactional
leprosy. Semin Cutan Med Surg. 26(2):126-30, 2007
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Microscopic Features
p
p
p
(Left) Lepromatous leprosy
demonstrates a grenz zone
in almost all cases, and also
shows a diffuse infiltrate of
foamy macrophages
called lepra or Vichrow cells)
that are often filled with bacilli,
which are easily seen with
special stains. (Right) Medium-
ower view of lepromatous
leprosy case demonstrates
a diffuse infiltration of the
arrector pili muscle by
the histocytic cells and
lymphocytes.
(Left) High-power view shows
how the prominent infiltration
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
of "spindle" histocytes in
leprosy can be confused with
a histocytic neoplasm .
(Right) High-power view of
skin biopsy demonstrates an
intense inflammatory infiltrate
composed of lymphocytes
in borderline lepromatous
leprosy. There are more
lymphocytes, and tendency to
form granulomas.
(also-
LEPROSY
(Left) Fite stain of an oral
lesion of lepromatous leprosy
demonstrates a striking,
diffuse proliferation of
ositive, red-staining bacilli
within foamy macrophages
(Virchow cells). (Right) High-
ower view of a Fite stain
demonstrates numerous acidfast bacilli (AFB) within lepra
. Borderline lesions
cells
typically demonstrate far
fewer AFB in tissue biopsies,
while tuberculoid leprosy
lesions typically will not show
demonstrable AFB by special
stains.
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Microscopic Features
p
p
p
g
p
p
Bacterial Infections: Morphological Diagnosis of Bacterial Infections
LEPROSY
(Left) A case of Lucio
henomenon shows
ulcerated skin nodules.
(Courtesy E. Kraus, MD.)
(Right) This biopsy of Lucio
henomenon shows a
thrombotic vasculopathy
attern with a large
thrombus in a vessel,
surrounding mononuclear
inflammation, and a mild
endothelial proliferation
that can be quite marked
at times. A Fite stain
demonstrates positivestaining acid-fast bacilli
within the thrombus and
vessel wall . (Courtesy D.
Scollard MD, PhD.)
(Left) High-power
view of borderline
leprosy demonstrates
a lymphohistiocytic
inflammatory infiltrate
surrounding and destroying
a nerve . (Courtesy
S. Billings, MD.) (Right)
Low-power view of a
case of borderline leprosy
demonstrates a nerve
surrounded by an epithelioid
ranuloma and numerous
lymphocytes. (Courtesy S.
Billings, MD.)
(Left) Biopsy from a
atient with tuberculoid
leprosy demonstrates deep,
epithelioid granulomas
surrounding neurovascular
bundles , also with
numerous lymphocytes .
(From DP Nonneoplastic
Derm.) (Right) Clinical
hoto of lepromatous
leprosy (LL) shows nodules
causing deformities of the
aural helix. LL is symmetrical,
bilateral, and often affects
other organs. Leprosy prefers
cooler areas of the body
(ears, nose, and peripheral
nerves). (Courtesy M.
Ramos-e-Silva, MD, PhD.)
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