GRANULOMATOUS LUNG DISEASE

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GRANULOMATOUS LUNG DISEASEINTERSTITIAL LUNG
DISEASE
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GRANULOMATOUS DISEASENecrotizing 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, Wegeners granulomatosis other
  angiitides

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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

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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

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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

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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
• gt 80 of TB toll in developing countries is in
  the economically most productive age-group
  (15-60 years)

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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

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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

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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 Langerhans type
  giant cells
• Mantle of B lymphocytes

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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
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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
  Potts disease, fallopian tubes, epididymis

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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 Rasmussens aneurysm
• Extrapulmonary complications amyloid

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Tuberculosis in the elderly immunocompromised

• TB in the elderly
• Disseminated miliary TB (non-reactive TB)
• little granulomatous response, necrosis, DAD
• TB in AIDS
• conventional morphology
• granulomas poorly formed
• opportunistic MAC from environment,
• spindle cell pseudotumours

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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)

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Necrotizing Granulomas other infectious causes

• Brucellosis
• Fungi Histoplasma, Coccidioides
• Cryptococcus, Blastomyces
• Dirofilaria

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SARCOIDOSIS

• A disease of unknown cause characterized by
  non-caseating 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
• BgtW, FgtM, but rare in American Indians, Eskimos
• Communicable agent suspected but as yet
  undiscovered

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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)

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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

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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

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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)

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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

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