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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
Mycobacteria are rod-shaped, nonsporulating, acid-fast
bacteria that are best identified on AFB stains. (Courtesy
Franz von Lichtenberg Collection of Infectious Disease
Pathology, BWH.)
TERMINOLOGY
Abbreviations
Mycobacterium tuberculosis (MTB)
Synonyms
Tubercle bacillus, Koch bacillus
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Definitions
Greek: "Myco" (fungi, for similarity of mycobacteria to
fungal growth on liquid media surfaces)
Latin: "Tuber" (lump or swelling)
Manifestations
Phthisis, consumption
Tuberculosis
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Humans are the only natural reservoir for
mycobacterial species M. tuberculosis, Mycobacterium
africanum, and Mycobacterium canetti
Most common in developing world
Cattle are also reservoirs of mycobacterial species
Mycobacterium bovis and Mycobacterium caprae
Seals are reservoir for Mycobacterium pinnipedii
Infectious Agents
Mycobacterium tuberculosis complex comprises several
species with > 99.9% identity
Members pertinent for human disease include M.
tuberculosis, M. africanum, M. canetti, M. bovis, M.
caprae, and M. pinnipedii
Transmission is mainly by inhalation of contaminated
droplets, though M. bovis infection can be transmitted
II
from cattle via undercooked meat or unpasteurized
milk
2
There are 4 examples of the hallmark lesion of
mycobacterial infection are shown: Granuloma with
centrally located Langerhans giant cells surrounded
by layers of inflammatory cells.
MTB are intracellular pathogens that subvert
phagosomal cell in order to persist and evade immune
system
Immunomodulatory components include cell wall,
which contains a unique complement of glycolipid
moieties
Includes lipomannan, lipoarabinomannan and
mycolic acids, responsible for acid-fastness of
organism
CLINICAL ISSUES
Presentation
Upon infection, MTB may establish itself in a
subclinical, latent state or immediately progress to
active disease (~ 10%)
Latent disease may reactivate in old age, in
periods of stress or nutrient deprivation, or upon
immunosuppression or HIV infection
Risk factors for active disease include extremes of age,
immunosuppression, and coinfection with HIV
Pulmonary tuberculosis
Typically, very early disease is asymptomatic
Progresses to nonspecific constitutional symptoms
Usually includes productive cough
Hemoptysis usually indicates endobronchial
erosion in advanced disease
Often diagnosed upon chest imaging that shows
infiltrates in lung apices or cavitation (CT or MR) in
advanced disease
Extrapulmonary tuberculosis can result from
contiguous or lymphohematogenous spread
Miliary tuberculosis: Progressive, widely
disseminated disease (foci resemble "millet seeds")
Central nervous system (CNS) tuberculosis
Common complication of childhood disease
Symptoms range widely, include headache,
vomiting, mental status changes, meningismus,
focal neurologic signs, and coma
60
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
Etiology
Members of MTB complex are rod-shaped, acid-fast,
aerobic, slow-growing intracellular pathogens that
subvert phagosomal cells in order to persist and evade
immune system
Humans are the only natural reservoir for
mycobacterial species M. tuberculosis, M. africanum,
and M. canetti
Most common in developing world
Drug resistance is a serious problem and some
infections are virtually untreatable
Transmission is mainly by inhalation of
contaminated droplets, though M. bovis infection can
be transmitted from cattle via undercooked meat or
unpasteurized milk
Key Facts
May establish itself in a subclinical, latent state, or
immediately progress to active disease (~ 10%)
Latent disease may reactivate in old age, in
periods of stress or nutrient deprivation, or upon
immunosuppression or HIV infection
Pulmonary tuberculosis is most common
manifestation
Extrapulmonary tuberculosis can affect virtually
any organ system and result from contiguous or
lymphohematogenous spread
Histopathologic hallmark is a necrotizing granuloma
with giant cells and epithelioid histiocytes
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Usually presents with nonspecific constitutional
symptoms and productive cough
CSF usually shows lymphocytic predominance,
high protein, and low glucose
Acid-fast bacilli (AFB) may be present on Gram
stain
Pleurisy: Most common in young children
Pericarditis: Most common in HIV(+) patients
Skeletal tuberculosis (Pott disease)
Occurs in 1/3 of cases
Typically begins on anterior aspect of vertebral
body
Spreads to disks and other vertebra
Tends to affect lower thoracic or lumbar spine
(also hips and knees)
Commonly progresses to paraspinal abscess (can
be extensive)
Lymphadenitis (scrofula)
Most common form of extrapulmonary
tuberculosis
HIV negative: Usually unilateral and cervical; no
systemic symptoms
HIV positive and AIDS: Often multifocal and
marked systemic symptoms
Commonly complicated by suppuration, sinus
formation, and enlargement of surrounding nodes
(which may represent immune activation rather
than spread)
Renal
Asymptomatic lesions common in pulmonary TB
Usually sterile pyuria
Advanced disease includes papillar necrosis,
uretal stricture, hydronephrosis, cavitation, and
autonephrectomy
Genitourinary
Males: Often a tender scrotal mass with draining
sinus; may have calcified foci in prostate
Females: Hematogenous spread commonly
involves endometrium and ovaries; may mimic
carcinoma in cervix or peritoneal carcinomatosis
Other extrapulmonary manifestations
Gastrointestinal: Can affect any part of GI tract
(also hepatic and pancreatic inflammation and
masses)
Peritoneal: Plastic and serous types
Cutaneous: Lupus vulgaris (most common form),
scrofuloderma
Other MTB complex organisms
M. africanum
Causes a tuberculosis-like (clinically and
histologically equivalent) disease predominantly
in West Africa
Patients affected with symptoms are usually
immunocompromised
Lacks "region of difference 9," which may be
related to differences in pathogenesis
M. canetti
Causes a tuberculosis-like (clinically and
histologically equivalent) disease predominantly
in Horn of Africa
Patients affected with symptoms may be
immunocompetent or immunocompromised
Species has a novel phenolic glycolipid and lipo-
oligosaccharide
M. bovis
Causes a tuberculosis-like (clinically and
histologically equivalent) disease after animal
exposure
Control is primarily through culling of affected
animals
Inherently resistant to pyrazinamide
M. caprae
Causes a tuberculosis-like (clinically and
histologically equivalent) disease after animal
exposure in Eastern Europe
Control is primarily through culling of affected
animals
Distinguished by molecular genotyping
techniques
M. pinnipedii
II
2
61
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
Causes a tuberculosis-like (clinically and
histologically equivalent) disease after exposure to
seals, guinea pigs, rabbits, or tapirs
Distinguished by molecular genotyping
techniques
Laboratory Tests
Tuberculin skin testing
Used screen to detect exposure by reaction to an
intradermal dose of purified protein derivative (PPD)
Interferon release assays
ELISA-based assay to determine the release of
interferon gamma in response to multiple, purified
MTB products
Does not cross-react with BCG, though may with
other mycobacterial species
Sputum
Acid-fast staining, culture, and direct detection or
organisms by PCR
In a suspected patient, 3 sputa are required to rule
out/rule in infection
Lumbar puncture
May demonstrate organisms (by culture or AFB
stain) in meningitis
High protein, low glucose, lymphocytic
predominance
Fine-needle aspiration
May show organisms in lymphadenitis
Often smear positive in HIV(+)
May need biopsy and culture to detect in HIV(-)
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Treatment
Surgical approaches
Mycobacterial lymphadenitis may have to be
surgically excised
Large lesions of any organ may be resected to
prevent catastrophic erosions (e.g., aorta)
Drugs
Several possible months-long, multi-drug regimens
available for active disease
Usually some combination of isoniazid, rifampin,
pyrazinamide, and ethambutol
Drug resistance is a serious problem in MTB
therapy and some or all commonly used agents
may be ineffective
Standard treatment for latent MTB infection consists
of 9 months of daily isoniazid
Prognosis
Excellent in immunocompetent individuals with drugsusceptible infections
Outcomes can be quite poor in ill/
immunocompromised patients, particularly if infected
with resistant strains
IMAGE FINDINGS
Radiographic Findings
Classically, MTB will show upper lobe involvement
II
with apical scarring
Miliary TB, pleural effusions, lobar pneumonias, and
hilar masses are also possible
2
CT Findings
Pulmonary sites may show cavitation
Nonpulmonary sites may show small (miliary)
disseminated nodules up to large solid or cavitary
lesions with variable calcification
MICROBIOLOGY
Morphologic and Biochemical
Characteristics
Acid-fast, aerobic rods
Culture
Slow growing
Doubling time may be > 20 hours
Time to detection is 2-8 weeks
Molecular Microbiologic Identification
Commonly by nucleic acid amplification test (NAAT)
MACROSCOPIC FEATURES
General Features
Lungs
Cavities, caseating (necrotic) zones, and old calcified
foci
Commonly involves hilar and mediastinal lymph
nodes
Lung lesions and hilar foci may both heal and
calcify (Ghon foci)
Extrapulmonary features
Widespread caseating granulomas
Peripheral involved lymph nodes tend to be in
supraclavicular fossa or posterior cervical triangle
Intestinal ulcers may be transversal, granular, and
punched out against smooth, hyperemic mucosa
(tubercles may proliferate along edges)
Peritoneal tuberculosis can develop from miliary
tubercles in omental fat or propagate from infected
abdominal lymph nodes or intestinal ulcers
Skeletal involvement commonly in lower thoracic
and lumbar vertebrae (Pott disease)
Also knees and hips
MICROSCOPIC PATHOLOGY
Histologic Features
Pulmonary
Most common site of both primary and reactivation
tuberculosis
Can involve airways, parenchyma, and pleura
Primary tuberculosis
Most commonly self-limited
Lung lesions and hilar foci heal and calcify (Ghon
foci)
Can be progressive
Hallmark lesion is caseating granuloma
Contain Langerhans giant cells with nuclei in
a horseshoe arrangement, as well as activated
epithelioid macrophages
62
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
As granulomas progress, center becomes necrotic
(caseous necrosis, coagulative necrosis speckled
with basophilic particles of hydroxyapatite)
With erosion into airways, exudative material
is available to be expressed and transmitted to
others
With erosion into blood vessels, may spread
widely
Extrapulmonary
Pericardial
Constrictive, constrictive-effusive, or effusive
pericarditis
Abdominal
Can spread via propagation to abdominal lymph
nodes
Intestinal tuberculosis may demonstrate clubbing
of villi, inflammatory infiltrates, and necrosis of
lamina propria and submucosa
Tuberculous hepatitis can manifest as caseating
granulomas as well as diffuse inflammatory and
fibrous lesions (usually in context of miliary TB)
Can involve virtually any other organ
Lymphadenitis
May occur in isolation from pulmonary or miliary
tuberculosis
Usually demonstrates well-formed granulomas
with scarce AFB
CNS
Caseating granulomas of brain parenchyma
Leptomeningitis
AFB are normally scarce except in AIDS patients;
can have dramatic, exudative CNS lesions with
dense colonies of AFB
Dermatologic
Lupus vulgaris: Rare, focal, chronic,
granulomatous dermatitis
Scrofuloderma: Ulcerative lesions arising from
contiguous spread of underlying affected lymph
nodes
Erythema induratum: Granulomatous panniculitis
with necrosis and vasculitis on posterior aspect of
legs
Skeletal
Granulomatous lesions with degeneration of bone
and disks
Commonly spreads into contiguous soft tissue
with abscess formation
DIFFERENTIAL DIAGNOSIS
Necrotizing Granulomatous Disease
Fungal infections
Negative AFB stain, positive stain for fungi on silver
or periodic acid-Schiff stain
Atypical mycobacteria
Positive AFB stain, must be differentiated using PCR
&/or culture methods
Sarcoidosis
Generally small, tightly circumscribed granulomas,
not necrotizing
May contain asteroid bodies or small calcifications
Granulomatosis with polyangiitis
Tends to feature more mixed inflammation, e.g.,
neutrophils, eosinophils
Has collagenolytic debris and evidence of
hemorrhage and small vessel vasculitis
Crohn disease
Granulomas tend to be small and nonnecrotizing,
confined to gastrointestinal tract
Other features of chronic colitis should be present
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
History of foreign birth, known exposures (prisons,
homeless, affected family member), or positive sputum
AFB should prompt AFB staining of tissue samples and
PCR/culture
Pathologic Interpretation Pearls
Mycobacteria on a standard AFB stain cannot be
reliably distinguished on morphology alone
Confirmation with culture &/or PCR is required for
definitive diagnosis
SELECTED REFERENCES
1. Fitzgerald DW et al: Mycobacterium tuberculosis. In Mandell
et al: Mandell, Douglas, and Bennett’s Principles and
Practice of Infectious Diseases. 8th Edition. Philadelphia:
Elsevier/Saunders. 2787-2818, 2015
2. Pai VV et al: A clinico-histopathological study of lupus
vulgaris: A 3 year experience at a tertiary care centre.
Indian Dermatol Online J. 5(4):461-5, 2014
3. Ntsekhe M et al: Tuberculous pericarditis with and without
HIV. Heart Fail Rev. 18(3):367-73, 2013
4. Sethuraman G et al: Cutaneous tuberculosis in children.
Pediatr Dermatol. 30(1):7-16, 2013
5. Wu Z et al: Diagnosis and treatment of hepatic
tuberculosis: report of five cases and review of literature.
Int J Clin Exp Med. 6(9):845-50, 2013
6. Wu RI et al: Staining for acid-fast bacilli in surgical
pathology: practice patterns and variations. Hum Pathol.
43(11):1845-51, 2012
7. Hunter RL: Pathology of post primary tuberculosis of the
lung: an illustrated critical review. Tuberculosis (Edinb).
91(6):497-509, 2011
8. Jin XJ et al: Histopathology and TB-PCR kit analysis in
differentiating the diagnosis of intestinal tuberculosis and
Crohn’s disease. World J Gastroenterol. 16(20):2496-503,
2010
9. Kradin RL et al: Pulmonary infections. In Kradin RL:
Diagnostic Pathology of Infectious Diseases. Philadelphia:
Elsevier/Saunders. 148-54, 2010
10. Hari S et al: Isolated tuberculosis of the pancreas diagnosed
with needle aspiration: a case report and review of the
literature. Trop Gastroenterol. 26(3):141-3, 2005
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
II
2
63
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
p
g
p
Gross and Microscopic Features
(Left) This specimen
demonstrates a solitary,
caseous, primary tuberculoma.
The majority of infections
do not progress to active
disease. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.) (Right) These lungs,
from a patient with advanced
ulmonary tuberculosis,
demonstrate both caseous
necrosis and cavitation
. (Courtesy Franz von
Lichtenberg collection of
Infectious Disease Pathology,
BWH.)
(Left) In reactivation
tuberculosis, lesions tend
to be subapical, such as
the caseating mass seen
here. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.) (Right) In tuberculosis,
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
necrotizing granulomas
are the histological equivalent
of caseous necrosis (a term
used only for the gross
appearance). (Courtesy Franz
von Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
(Left) Here, hematogenous
spread has caused miliary
tubercles to form in the
omental fat. Note the rim of
lymphocytes . (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Right) Intestinal ulcers in
tuberculosis are transversal,
ranular, and punched out
against smooth, hyperemic
mucosa. They undermine
the mucosa with tubercles
roliferating along the edge
. (Courtesy Franz von
Lichtenberg Collection of
II
2
Infectious Disease Pathology,
BWH.)
64
MYCOBACTERIUM TUBERCULOSIS COMPLEX INFECTIONS
g
g
g
g
Microscopic Features
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
(Left) Lupus vulgaris is a
ranulomatous dermatitis
caused by M. tuberculosis.
Epidermal acanthosis
and numerous tubercles
are seen with giant cells
. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.) (Right) Despite
clear granulomas, AFB
may be scarce and require
a painstaking search in
case of tuberculosis. Cases
with innumerable bacteria
are possible. (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Left) In active, pulmonary
tuberculosis, granulomas are
mixed with exudative lesions,
including purulent bronchial
content . (Courtesy Franz
von Lichtenberg Collection
of Infectious Disease
Pathology, BWH.) (Right)
Both bronchioles and alveoli
are targets of necrotizing
ranulomatous inflammation
in tuberculous
bronchopneumonia.
Note areas of necrosis
. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
(Left) Leptomeningitis may
occur in extrapulmonary
tuberculosis, such as the
early-stage tubercle shown
here . (Courtesy Franz
von Lichtenberg Collection
of Infectious Disease
Pathology, BWH.) (Right)
Hematogenous spread of M.
tuberculosis can establish
infection with accompanying
ranulomas in distant
sites. An AFB stain should
be performed whenever
ranulomas are present in
tissue. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
II
2
65
MYCOBACTERIA OTHER THAN TUBERCULOSIS INFECTIONS
A skin punch biopsy from a patient who presented
with several weeks of AFB-positive nodules is shown,
with areas of superficial abscess formation and deep
organized chronic inflammation .
TERMINOLOGY
Abbreviations
Mycobacterium avium complex (MAC)
Nontuberculous mycobacteria (NTM)
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
INFECTIOUS AGENTS
Mycobacterium avium Complex (MAC)
Includes Mycobacterium avium and Mycobacterium
intracellulare
Widely present in environment
Transmission is by inhalation or ingestion of
contaminated food (particularly milk) or water
Pulmonary disease
In HIV(+) patients
Typical manifestation is upper lobe fibronodular
and cavitary disease (may be quite large)
Immunocompetent adults (often older women,
Lady Windermere disease)
Radiographically detected as "tree-in-bud"
opacities
Risk factors include underlying pulmonary
pathology, steroid use
Disease associated with pigeon exposure and hot
tub exposure ("hot tub lung")
May be hypersensitivity pneumonitis or direct
infection
Clinical course is subacute/chronic and presents
with constitutional symptoms and productive
cough
Lymphadenitis
Usually in children < 5 years old
Nontender, firm, unilateral, enlarged cervical nodes
(can also be abdominal or thoracic)
II
Can be quite large
Often associated with ulceration and fistula
formation
2
High magnification of a tissue section from a patient with
atypical Mycobacterium infection demonstrates giant
cells of various morphologies admixed with epithelioid
histiocytes .
Disseminated disease
Often in HIV(+) patients (advanced disease)
Also primary immunodeficiencies and hairy cell
leukemia
High fever, weight loss, anemia, abdominal pain,
diarrhea, hepatosplenomegaly
Disease is always primary; there have not been any
reported cases of MAC reactivation
Rapid-Growing Nontuberculous
Mycobacteria (NTM)
Defined as organisms that form colonies within 7 days
Numerous species
Nonpigmented: Mycobacterium fortuitum,
Mycobacterium chelonae/abscessus
Late-pigmenting: Mycobacteriumm smegmatis,
Mycobacterium goodii
Early-pigmenting: Mycobacterium flavescens,
Mycobacterium vaccae
M. fortuitum, M. goodii, M. abscessus, and M. smegmatis
have been associated with lipoid pneumonia and
achalasia
M. fortuitum, M. abscessus, and M. chelonae, among
others, have been associated with medical/cosmetic
procedures such as mammoplasty and liposuction as
well as treatment in nail salons
Slow-Growing NTM
Defined as organisms that form colonies after 7 days
Species include Mycobacterium kansasii, Mycobacterium
xenopi, Mycobacterium simiae, Mycobacterium ulcerans,
Mycobacterium marinum, Mycobacterium haemophilum,
and Mycobacterium gordonae
M. kansasii and M. gordonae can cause an upper lobe,
fibronodular cavitary disease similar to MAC
Symptoms can be nonspecific and include chronic
cough
66
MYCOBACTERIA OTHER THAN TUBERCULOSIS INFECTIONS
Constitutional symptoms may be less prominent
than in Mycobacterium tuberculosis (MTB) or MAC
infection
M. marinum classically causes "fish tank granuloma,"
papules and ulcerations on hands and arms associated
with cleaning a fish tank
M. ulcerans is etiologic agent of Buruli ulcers, painless,
disfiguring, necrotizing ulcers usually found on
extremities of children in developing world
Characteristically have wide area of surrounding
erythema
Necrosis is caused by the toxin mycolactone
M. haemophilum is an increasingly recognized cause
of skin nodules, sometimes associated with soft tissue
abscess, fistulas, and osteomyelitis
Often on extremities of children
M. xenopi is a frequent cause of osteomyelitis, though
other rapid- and slow-growing NTM may also be
causative
CLINICAL IMPLICATIONS
Laboratory Tests
MAC
Sputum cultures can be positive in patients without
disease (need to be accompanied by clinical
symptoms, positive imaging, etc.)
Smears are not often positive
Disseminated disease is diagnosed by culture
Lymphadenitis is assayed by excisional biopsy
(needle aspirations are generally avoided due to
complications such as fistulas)
NTM
Smears can be helpful for identifying acid-fast M.
ulcerans from Buruli ulcers
Treatment
MAC: Difficult to treat, requires a multiple-drug
regimen given over many months
Agents include: Clarithromycin, ethambutol,
rifampin, amikacin, and streptomycin
Isolated lymphadenitis often treated with surgical
excision alone
NTMs can be difficult to treat with antimicrobials;
standard treatment varies by species
Prognosis
MAC: Varies widely
Excellent in childhood lymphadenitis
Extremely poor in disseminated disease in AIDS
patients
MICROBIOLOGY
Morphologic and Biochemical
Characteristics
Mycobacteria are aerobic, rod-shaped, non-sporeforming, acid-fast organisms
MAC colonies are usually tan or light yellow
NTMs can be either pigmented or nonpigmented
Culture
MAC colonies are slow growing (2-3 weeks on agar)
M. marinum, M. ulcerans, and M. haemophilum
characteristically grow best at lower temperatures
(28-30 C)
M. haemophilum additionally requires hemoglobin,
hemin (factor X), or ferric ammonium citrate and so
may often not be detected if standard culture is used
Molecular Microbiologic Identification
MAC organisms are often identified based on nucleic
acid amplification tests (NAATs) such as Gen-Probe
NTMs may have to be sequenced for a species-level
identification
Targets include 16S, hsp65, and rpoB
MACROSCOPIC FINDINGS
Rapid Growers
Infections may present as small to large abscess with
purulent centers
Slow Growers
Classic granulomatous inflammation with caseous
(yellow, cheese-like) appearance
May include dense fibrous capsule and calcifications
in older lesions
Spindle cell nodules of MAC may appear white and
solid like tumors
MICROSCOPIC FINDINGS
Dermatologic
Wide range of manifestations by species and host
immune status
Most characteristic pattern involves granulomas
with necrotic, neutrophilic centers surrounded by
histiocytes and peripheral lymphocytic infiltrate
Granulomas tend to be less tightly formed than in
M. tuberculosis infection
M. marinum is commonly associated with epidermal
changes such as acanthosis, pseudoepitheliomatous
hyperplasia, and exocytosis
Necrosis may be prominent
In immunosuppressed, infiltrate tends to be deeper
(subcutaneous), more diffuse, and associated with
abscess
Granulomas may be more prominent in
immunocompetent patients
Necrotizing folliculitis reported with M. chelonae
infection
M. ulcerans (Buruli ulcer)
Extensive necrosis of subcutaneous tissue with
minimal inflammatory reaction
Numerous AFB may be observed
Pulmonary
MAC lung infection in immunocompromised may
show features similar to M. tuberculosis infection
Cavitating lesions, necrotizing granulomas, etc.
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
II
2
67
MYCOBACTERIA OTHER THAN TUBERCULOSIS INFECTIONS
With increasing immunosuppression, pattern may
be of loose histiocytic infiltrate, with many obvious
intracellular AFB
MAC lung infection in immunocompetent patients
(older women)
Often in right middle lobe
Extensive swaths of nonnecrotizing epithelioid
histiocytes
Well-organized necrotizing granulomas also
reported
Likely to accompany extensive underlying
pulmonary pathology
MAC hypersensitivity pneumonitis: "Hot tub lung"
Characterized by well-formed granulomas, often
peribronchial
Organisms rarely detected
M. kansasii can cause particularly severe lung
pathology (especially in HIV[+] patients)
Features can include necrotizing granulomas,
suppurative abscess, spindle cell proliferations, and
foci of granular eosinophilic necrosis
Organisms have a characteristic appearance
described as "coarsely beaded, folded, or crosslinked" curved ends
Lymphadenopathy
Scrofula
Involved lymph nodes have multiple granulomas
with necrotic centers
Overlying dermis can be involved by extensive
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
inflammatory infiltrate
AFB are observed infrequently; culture is usually
necessary for definitive diagnosis
MAC lymphadenitis in HIV(+) patients may be more
marked by histiocytic infiltrate
AFB may be present in large numbers within
histiocytes
Mycobacterial spindle cell pseudotumor
May be found in lymph nodes as well as other sites:
Lung, skin, brain, etc.
Spindle cells are foamy histiocytes containing many
mycobacteria, but may be mistaken for neoplasm
Osteomyelitis
Fairly common
Direct inoculation in immunocompetent (usually
nosocomial)
Hematogenous spread in immunosuppressed
Granulomatous inflammation in immunocompetent
patients
Mixed inflammatory infiltrate
Necrosis
Ancillary Testing of Tissue
AFB stain (Ziehl-Neelsen, Kinyoun, and Fite stains)
Number of AFB seen on ZiehlNeelsen (standard
AFB stain) or Kinyoun (modified AFB which stains
Nocardia) may be few/scattered to large numbers
Fite (modified by addition of vegetable oil) for
organisms such as Mycobacterium leprae
Because of possible long culture times, suspected
and clearly positive AFB stains should be confirmed
with molecular testing
PCR with sequencing
Consensus primers to amplify genus Mycobacterium
with speciation by sequencing
DIFFERENTIAL DIAGNOSIS
Other Granulomatous Infections
Mycobacterium tuberculosis infection (positive AFB
stain, requires culture/PCR to distinguish)
Fungal infections (negative AFB stain, positive silver
stains for fungi)
Bartonellosis (negative AFB stain, positive on Steiner
stain or by PCR)
Other Abscesses
Bacterial abscess (negative AFB stain, positive Gram or
silver stain, culture/PCR to confirm)
Commonly, Staphylococcus, Streptococcus in skin
Ruptured epidermal cyst (negative AFB stain, keratin)
Injection site reaction (negative for AFB, sterile)
SELECTED REFERENCES
1. Brown-Elliott BA et al: Infections caused by
nontuberculous mycobacteria other than Mycobacterium
avium complex. In Mandell et al: Mandell, Douglas, and
Bennett’s Principles and Practice of Infectious Diseases. 8th
Edition. Philadelphia: Elsevier/Saunders. 2844-52, 2015
2. Gordin FM et al: Mycobacterium avium complex. In Mandell
et al: Mandell, Douglas, and Bennett’s Principles and
Practice of Infectious Diseases. 8th Edition. Philadelphia:
Elsevier/Saunders. 2832-43, 2015
3. O’Connell ML et al: Lung manifestations in an autopsybased series of pulmonary or disseminated nontuberculous
mycobacterial disease. Chest. 141(5):1203-9, 2012
4. Kradin RL et al: Pulmonary infections. In Kradin RL:
Diagnostic Pathology of Infectious Diseases. Philadelphia:
Saunders Elsevier. 152-5, 2010
5. Cooke RA: Atypical mycobacterial infections, rickettsial
infections, yaws, and colonic spirochetosis. In Cooke, RA:
Infectious Diseases: Atlas, Cases, Text. Sydney New York:
McGraw Hill. 146-155, 2008
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Other
MAC and NTMs may affect virtually any organ in
disseminated disease
General histopathologic feature is a necrotizing
granuloma, but varies widely with organism and
immune status of patient
MAC is most common agent associated with immune
reconstitution syndrome in HIV infection
MYCOBACTERIA OTHER THAN TUBERCULOSIS INFECTIONS
g
g
g
g
Microscopic Features
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
(Left) Low-power view shows
a large granulomatous mass
with central neutrophilic
abscess formation
surrounded by dense
ranulomatous inflammation
in a lymph node of
a patient with atypical
Mycobacterium infection.
(Right) High magnification
shows epithelioid
ranulomatous inflammation
with central neutrophilic
abscess formation in a
lymph node of a patient with
atypical Mycobacterium
infection.
(Left) A section from a welldeveloped skin abscess in
a patient with a chronic
history of lesions for several
weeks demonstrates large
collections of neutrophils
in a case of atypical
mycobacterial infection.
(Right) An acid-fast
stain from a patient with
Mycobacterium kansasii
infection of the skin
demonstrates individual
and aggregates of the
organisms both free in tissue
and within macrophages.
(Left) A section from a
skin abscess in a patient
with a fulminant history
demonstrates large
collections of neutrophils
admixed with necrosis and
edema in a case of rapidly
rowing mycobacteria.
(Right) An acid-fast stain
from a patient with rapidly
rowing Mycobacterium
fortuitum infection of the
skin demonstrates individual
and clumps of the
organisms free in tissue.
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