Transcript GRANULOMATOUS DISEASE & INTERSTITIAL LUNG DISEASE

GRANULOMATOUS
LUNG DISEASE
&
INTERSTITIAL
LUNG DISEASE
GRANULOMATOUS DISEASE
Necrotizing vs non-necrotizing
• Most necrotizing granulomatous disease is
infectious
• Responsible organism usually demonstrable in
tissue
• All specimens should be cultured
• Non-infectious granulomatous inflammation –
sarcoidosis, Wegener’s granulomatosis & other
angiitides
TUBERCULOSIS (Robert Koch – 1882)
The mycobacteria that cause TB in man:
• Mycobacterium Tuberculosis – droplet
infection = inhalation of infective droplets
coughed or sneezed by a patient with TB
• Mycobacterium Bovis – drinking milk from
infected cows – intestinal and tonsillar lesions
• M. Avium & M. Intracellulare (MAC complex)
cause opportunistic infection in IC
TUBERCULOSIS
• Mycobacteria are Aerobic organisms
Difficult to stain - waxy cell wall
- scanty in tissue
- slow growth in culture
- PCR
Difficult to kill
They have no toxins or histolytic enzymes
they inhibit phagosome-lysosome fusion and
killing by macrophages
they induce delayed hypersensitivity
TUBERCULOSIS - Epidemiology
• Developed countries – considerable fall in
incidence and mortality in 20th century
• A disease of the elderly – recrudescence of
quiescent infection acquired in youth
• Recent resurgence – AIDS, urban deprivation,
immigrant & refugee populations
TUBERCULOSIS - Epidemiology
• 1/3 world population infected (1700 million)
• 8 million new cases every year - 95% in
developing countries
• 3 million deaths every year - largest cause of a
death from a single pathogen
• TB kills twice as many adults as AIDS, malaria
and other parasitic diseases combined
• > 80% of TB toll in developing countries is in
the economically most productive age-group
(15-60 years)
TUBERCULOSIS – The impact of
HIV infection
• Alarming resurgence, poorer communities, drug abuse
• Multidrug resistant strains have emerged
• 6 million people world-wide have dual infection,
majority in sub-Saharan Africa
• HIV infection – particularly aggressive TB –
widespread dissem. & poor host response
• HIV infection promotes infection with opportunistic
mycobacteria
TUBERCULOSIS
Primary TB
• First time infection
• Formerly found mainly in children, now
encountered in adults
Postprimary TB
• Adult type
• Previously sensitized fresh infection or
reactivation of a dormant primary lesion
PRIMARY TB - Ghon Focus
• Inhaled tubercle bacilli ingested by alveolar
macrophages
• Macrophages with bacilli aggregate, forming
microscopic nodules that deform architecture
• Development of T-cell mediated immunity CD4 (helper)
& CD8 (cytotoxic)
• CD4 – interferon – secretory changes in macrophages –
epithelioid histiocytes
• CD8 – kill macrophages – resulting in caseous necrosis
• Fusion of macrophages to form Langerhan’s type giant
cells
• Mantle of B lymphocytes
GHON COMPLEX
(1) Parenchymal subpleural lesion at
the subpleural fissure between upper
and lower lobes
&
(2) the enlarged hilar / mediastinal
caseous lymph nodes draining the
parenchymal focus
PRIMARY TB – Possible outcomes
• Resolution – development of a fibrous capsule - eventually
calcified scar
• Progression- erosion into bronchus – cavitation –
dissemination within bronchial tree (galloping consumption!)
• Pleural spread – effusion, TB empyema
• Compression by caseous nodes of bronchus or trachea –
collapse, compression, stridor
• Haematogenous dissemination = Miliary TB
cervical lymph nodes (scrofula), meninges (tuberculous
meningitis), kidneys, adrenals, bones (tuberculous osteomyelitis)
[veterbral TB = Pott’s disease], fallopian tubes, epididymis
POSTPRIMARY TB
Endogenous vs Exogenous
Associations - alcoholism, diabetes, silicosis,
immunosuppression
Pulmonary
Apical disease
Caseous pneumonia in lower lobes
Cavities – ca, colonization, bronchiectasis
Pleural & pulmonary fibrosis
Obliterative endarteritis of pulmonary & bronchial aa –
but “Rasmussen’s aneurysm”
Extrapulmonary complications – amyloid
Tuberculosis in the elderly &
immunocompromised
TB in the elderly
Disseminated miliary TB – (non-reactive TB)
little granulomatous response, necrosis, DAD
TB in AIDS
1. conventional morphology
2. granulomas poorly formed
3. opportunistic MAC from environment,
spindle cell pseudotumours
TB – Skin tests & vaccinations
• Old tuberculin – now purified protein
derivative (ppd)
• Intradermal injection – Mantoux
• Multi-pronged devices – Heaf test
• Positive reaction indicates that a person has
been infected by tubercle bacillus
• Prophyllactic immunization with strain of low
virulence – Bacillus Calmette Guerin (BCG)
Necrotizing Granulomas
other infectious causes
• Brucellosis
• Fungi – Histoplasma, Coccidioides
Cryptococcus, Blastomyces
• Dirofilaria
SARCOIDOSIS
• A disease of unknown cause characterized by noncaseating granulomas in many tissues & organs
• Lungs, lymph nodes, spleen, liver, bone marrow, skin,
eye, salivary glands and less frequently – heart,
kidneys, CNS, endocrine glands – pituitary
• Occurs worldwide, more prevalent at higher latitudes –
Scandinavia, northern Europe and North America
• B>W, F>M, but rare in American Indians, Eskimos
• Communicable agent suspected but as yet undiscovered
SARCOIDOSIS
• Enhanced cellular hypersensitivity at involved sites –
but depressed elsewhere
• Increased CD4 lymphocytes in the lung
• Clinical: mild non-specific chest complaints, cough,
dyspnoea
1/3 – Erythema nodosum
Increased serum Ca, ACE, gammaglobulins
• Radiographic Staging:
I
Hilar adenopathy alone (best)
II
Hilar adenopathy & parenchymal infiltrates
III
Parenchymal infiltrates alone (worst)
SARCOIDOSIS in the lung
Non-caseating granulomas
• Tight clusters of epithelioid histiocytes and occassional
MNGCs
• Tight rim of concentric fibroblasts , scattered
lymphocytes (naked granulomas)
• Laminated concretions – Schaumann Bodies
• Stellate inclusions – Asteroid Bodies
Distribution – along lymphatics (TBBx)
• Granulomatous vasculitis
DDx – infection, berylliosis, HP, IVDA, adjacent to
tumour / lymphoma
INTERSTITIAL LUNG DISEASE
• A heterogeneous group of non-neoplastic disorders
resulting from damage to the lung parenchyma by
varying patterns of inflammation and fibrosis
• Interstitium (space between the epithelial and
endothelial BM) - primary site of injury
• These disorders frequently also affect the airspaces,
airways and vessels
• Clinical – Radiology – Pathology correlation NB
• Aetiology / associations: idiopathic, collagen vascular
disease, drugs & toxins, environmental
INTERSTITIAL LUNG DISEASE
• Usual interstitial pneumonia (UIP)
aka Cryptogenic fibrosing alveolitis (CFA)
aka Idiopathic pulmonary fibrosis (IPF)
Vs.
The others:
Non-specific interstitial pneumonia (NSIP)
Organizing pneumonia (OP)
Respiratory bronchiolitis (RB)
Desquamative interstitial pneumonitis (DIP)
Lymphocytic interstitial pneumonitis (LIP)
Usual Interstitial Pneumonia
• Patchy lung involvement – worst at bases,
subpleural & paraseptal distribution
• Dense fibrosis – remodelling of lung
architecture – “honeycombing”
• Fibroblast foci
• Gradual onset of symptoms: dyspnea, non-prod
cough
• Median survival 2.5 – 3.5 years