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Pathology Lung


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Hypersensitivity reaction to the fungus aspergillus fumigatus present in endobronchial mucus plugs.

Aetiology: include associations, risk factors

Asthmatics and cystic fibrosis.


Allergic response triggers intense airways inflammation with eosinophils and the formation of mucous plugs. Inflammation leads to proximal bronchiectasis and fibrotic lung disease.

Macroscopic Pathology:

Cylindrical bronchiectasis.

Microscopic Pathology:

Muco-inflammatory contents with occasional fungal hyphae on special stains.

Clinical Presentation:

Wheeze, productive cough, dyspnoea; CXR shadows; eosinophilia.


Bronchiectasis; fibrosis.



Asthma is a chronic inflammatory disorder of the airways , resulting in paroxysmal, reversible airways narrowing, usually triggered by a stimulus.


Various classification systems
- clinical: mild intermittent / mild / moderate / severe persistent.
- stimulus: intrinsic / extrinsic
- others: occupational / drug induced / seasonal / exercise induced.


V. common (up to 10% population in industrialised societies).

Aetiology: include associations, risk factors

1. Genetic predisposition to type 1 hypersensitivity (atopy).
2. Viral respiratory tract infections.
3. Pollution: sulphur dioxide; ozone; nitrogen dioxide.
4. Aspirin
5. Ocuupational: organic / chemical dusts.

Rare: Association with systemic disorder – Churg-Strauss syndrome.


3 factors contribute to obstruction:

1. bronchial muscle constriction
2. mucosal swelling
3. increased mucous production.

Extrinsic(atopic) asthma

Sensitization to inhaled allergen  inflammatory cells infiltrate bronchioles (mast cells)  re-exposure triggers Type 1 hypersensitivity reaction (release of mediators from mast cells)  bronchoconstriction; increased capillary permeability (mucosal swelling); inc. mucus production; recruited WC’s  late phase of more persistent narrowing and mucosal damage.

Ie: sensitized  exposed  acute phase (type 1 HS)  late phase (established inflammation).

Macroscopic Pathology:

Hyperinflated lungs
Mucous plugs

Microscopic Pathology:

Bronchioles: Thickening BM; edema, inflammatory infiltrate; hypertrophied bronchial smooth muscle.
Sputum: Curschmann spirals (whorls of shed brochial epithelium in mucous plugs); eosinophils; Charcot-Leyden crystals (eosinophil membrane protein)

Clinical Presentation:

Recurrent episodes of SOB, wheeze, chest tightness and cough.


Airleak: pneumothorax / pneumomediastinum.
Collapse: mucous plugging.



1. Permanent dilatation of bronchi and bronchioles
2. caused by destruction of the muscle and elastic tissue,
3. resulting from chronic necrotising infections.


Appearance: cylindrical / saccular


Depends on cause.

Aetiology: include associations, risk factors

Congenital: Kartagener’s; cystic fibrosis; immune deficiency –
Hypogammaglobulinaemia; Intralobar sequestration.
Post-infectious: Necrotising pneumonia.
Bronchial Obstruction: Tumour; foreign body; ABPA
Chronic aspiration
Collagen vascular disease.


Obstruction and infection are main factors.
Obstruction  normal clearing mechanisms impaired  pooling secretions distal to obstruction  inflammation airway  superimposed infection  necrosis, fibrosis, dilatation of bronchial walls.

Macroscopic Pathology:

Usually affects lower lobes bilaterally, particularly vertically oriented airways (gravity resistance to mucous clearance); unless: due to tumour / FB – can be very localised.
See bronchioles within 2-3cm of plueral surface / bigger than adjacent pulmonary arteries.

Microscopic Pathology:

Intense inflammatory exudate in wall of bronchi/bronchioles.
Necrotizing ulceration.

Clinical Presentation:

Severe persistent productive cough. Copious foul smelling sputum.


Local: Acute: Pneumonia; abscess; empyema; haemoptysis (bronchial aa.)
Chronic: Amyloidosis; Cor Pulmonale.
Systemic: metastatic abscess; sepsis.
Definition: Bacterial Infection of the lung parenchyma characterized by patchy consolidation resulting from bronchial spread into the bronchovesicular interstitium and adjacent centrilobular alveoli.

Epidemiology: Common,
age peak infants and elderly

Pathogenesis: Pathogens:
1) staphylococci
2) streptococci
3) strep pneumonia
4) Hemophilus influenzae

Macroscopic Pathology: Site 1) unilobar
2) Multilobar
3) Patchy with centrilobular distribution

Microscopic Pathology: Consolidated area of acute suppurative inflammation
Acute Inflammation
1) suppurative exudate fills the airways, peribronchial interstitium, adjacent alveoli
2) Inflammatory cell neutrophils predominate
3) Necrosis variable cause lung abscesses

1) Chronic Inflammatory cells lymphocytes, macrophages, fibroblasts
2) Fibrosis interstitial-alveolar fibrosis

Infant Subtype variant form of bronchopneumonia, Pathogens E. coli Group B haemolytic strep. Acute inflammation confined to the interstitium. Alveoli relatively spared-mimics interstitial pneumonia

Clinical Presentation: Cough, fever, chest pain

Complications: Abscess formation, empyema, suppurative pericarditis, septicaemia, distant seeding

Management: Antibiotics Progress Chest X-Rays
Goodpasture Syndrome
Definition: - uncommon immunologic condition characterised by the simultaneous appearance of proliferative, usually rapidly progressive glomerulonephritis and a necrotizing haemorrhagic interstitial pneumonitis

Incidence & Epidemiology:

- average age 26
- most cases occur in teens and twenties
- M:F 7:1

Aetiology & Pathogenesis:

- renal and pulmonary lesions are consequence of antibodies evoked by antigens present in glomerular and pulmonary basement membranes
antibodies to alpha segment of collagen IV
- trigger initiating the anti-basement membrane antibodies is still unknown

- possible causative agents may be
- viruses
- hydrocarbon solvents
- smoking (cofactor)

- assoc. with HLA-DR2 subtype

Macroscopic Pathology:

- Lungs
- are heavy, with areas of red-brown consolidation

- Kidneys
- may be enlarged

Microscopic Pathology:

- Lungs
- acute focal necroses of alveolar walls
- assoc. with intra-alveolar haemorrhages, fibrous thickening of the septa
- hypertrophy of of lining septal cells is seen
- organisation of blood in the alveolar spaces
- the alveoli often contain haemosiderin stain macrophages
- immunofluorescence shows linear deposits of immunoglobulins along BM

- Kidneys
- characteristic findings of focal proliferative glomerulonephritis
- OR crescentic glomerulonephritis in rapidly progressive types
- linear deposits of Ig are also seen


- respiratory symptoms begin first
- principally haemoptysis
- then pulmonary consolidations
- then get renal manifestations
- rapidly progressive renal failure
- haematuria

- treatment
- plasma exchange


- uraemia
- significant pulmonary haemorrhage / consolidation -> respiratory failure
- anaemia
- hepatosplenomegaly
- systemic hypertension


- good
- has improved significantly with improved treatment
Lobar pneumonia
Definition: An acute bacterial infection of the lung parenchyma affecting the majority/entire lobe characterized by confluent consolidation and resulting from centrifugal alveolar spread via the pores of Kohn and canals of Lambert

Epidemiology: Uncommon

Aetiology: age peak infants and elderly, less prevalent du to Abs

Pathogenesis: Pathogens:
1) Strep pneumonia 90-95%
2) Klebsiella
3) Staph

Macroscopic Pathology: Site 1) unilobar
2) Multilobar
3) Patchy with centrilobular distribution

Airborne spread via bronchial tree, alveolar inflammation, extensive air space spread via the pores of Kohn and canals of Lambert. Limited by pleura and fissures.

Microscopic Pathology: Stages of the disease
1) Congestion-first 24 hours
2) Red hepatization exudates of neutrophils and red blood cells
3) Grey hepatization
accumulation of fibrin in alveoli
RBCs and neutrophils disintegrate progressive suppurative exudate
4) Resolution
lung normal lung parenchyma
pleura fibrosis scarring

Clinical Presentation: Cough, fever, chest pain

Complications: Abscess formation Staph, Klebsiella, Strep,
organization lung fibrosis

Management: Antibiotics Progress Chest X-Rays

Prognosis: <10% death rate death usually related to complications
Primary Lung carcinoma
Definition: - malignant neoplasm arising from the respiratory epithelium in the lower airways

Classification: -bronchogenic 90-95%
Histologic Types
- 1) Squamous cell 35%
- 2) Adenocarcinoma 25%
- bronchial derived
- brochioalveolar
- 3) Small cell 25% (oat cell, intermediate, combined)
- 4) Large Cell 13% - undifferentiated, giant cell, clear cell
- bronchial carcinoid 5%
- other 2-5% eg mesenchymal, lymphoproliferative

- Simple Classification divides into Small Cell Lung cancer and Non-Small Cell Lung Cancer
- important, as SCLC is radiosensitive/chemosensitive

- peak incidence in 6th and 7th decades (only 2% before age 40)
- 20% of all male cancers, and 10% of female cancers,
- M:F ratio 2:1 (increasing frequency in females related to increased incidence of smoking)

- 1) Smoking- average (<20/day) smokers have 10-fold increased risk, heavy (>40/day)
smokers have 20-fold increased risk

- 2) Industrial Hazards
- Asbestos
- 5 times increased risk for non-smokers, 90 times for smokers
- latent period = 10 to 30 years
- all carcinogens are characterised by long tumour latency period and tendency to
produce squamous and large cell anaplastic tumours

- 4) Genetic
- occasional familial clustering

- 5) Scarring- usually adenoCa

carcinoma begins as in situ atypia and then progressive to a small thickening of bronchial mucosa and then a warty excrescence
- following which, the tumour may then
- 1) continue to grow intraluminally as a fungating mass
- 2) penetrate the wall of the bronchus - infiltrating
- 3) continue to grow along a broad front to produce a cauliflower like, intraparenchymal mass

Macroscopic Pathology:
- most lesions arise in larger bronchi,
- peripheral lesions are predominantly adenoCa
- tissue is usually grey-white and firm, with focal necrosis and haemorrhage in larger tumour
- cavitation may occur (esp. in SCC)

Microscopic Pathology:
- 1) Squamous (35-50%)
- most closely correlated with history of smoking (more common in men)
- production of keratin and inter-cellular bridges in well-differentiated lesions
- ‘field effect’
- local growth is more rapid than other types and tends to metastasise

- 2) Adenocarcinoma (15-35%)
- M=F
- tends to produce smaller, more peripheral lesion
- well-differentiated, tumour shows obvious glandular elements, others show papillary
formation, while others are more solid
- cuboid-columnar cells
- 80% contain mucin
- bronchioalveolar type characteristic lepidic growth pattern

- 3) Small Cell (20-25%)
- Oat cell - small distinctive cell, round or oval, with little or no discernable cytoplasm
- cells frequently contain neurosecretory granules (APUD type)
- thought to have endodermal rather than neural crest origin
- strong association with smoking
- metastasize widely and early (primary often not found) esp. brain

- 4) Large Cell (10-15%)
- larger, more polygonal cells and vesicular nuclei
- probably represent unrecognisable poorly-differentiated SCCs and adenocarcinoma

Clinical Presentation:
- cough 75%, with haemoptysis in 50%
- weight loss 40%
- chest pain 40%
- dyspnoea 20%
- paraneoplastic syndrome
- ADH/ACTH is usually small cell, while hypercalcaemia is usually SCC
- Myasthenia Gravis, due to small cell, lambert eaton syndrome

- Intra-pulmonary
- obstructive emphysema atelectasis
- drowned lung
- distal suppuration and abscess formation
- Local Extra-pulmonary
- SVC obstruction
- pleural or pericardial involvement
- brachial plexus and sympathetic involvement (pancoast)
- oesophageal obstruction and fistula formation
- Distant metastases
- adrenal in over half
- also bone, brain (esp. small cell) and liver NB lymphangitis

Management: TNM staging

- overall 5 year survival is 10-15% poor
- virtually nil survival is lesion is in a main bronchus
- SCC and adenoCa tend to remain localised -> slightly better prognosis
- only 20-30% have lesions deemed surgically resectable at diagnosis. This group has a 30-50% 5 year survival, excluding small cell tumours
- small cell precludes surgery
- untreated survival time is 6-17weeks while treated is about 1 year
Malignant Mesothelioma
A malignant neoplasm of mesothelial lining, which may arise in pleura (most commonly), peritoneum or pericardium (rarely).
Classified according to site of origin (eg pleural or peritoneal). Also accoring to predominant cell type: epithelioid, sarcomatoid, or mixed.
90% have a history of asbestos exposure. Lifetime risk of up to 10% after heavy asbestos exposure, with a 25-45 year latent period. No association with smoking. NB the risk of lung carcinoma exceeds the risk of mesothelioma in asbestos workers. Peritoneal mesothelioma is associated with heavy asbestos exposure.
As discussed, the primary cause is asbestos exposure. The remaining cases are idiopathic.
Deletions in multiple chromosomes have been found in mesothelioma cells. P53 accumulation can be detected immunohistochemically. Some studies have demonstrated the presence of simian virus SV40 (which is a potential carcinogen) in mesothelioma, but the significance of this is controversial.
Extensive pleural thickening, associated with pleural effusion and direct invasion of adjacent thoracic structures. The affected lung is often encased.
Biphasic cell population, with epithelioid and sarcomatoid cells. Sarcomatoid cells are spindle-shaped and resemble fibrosarcoma. Epithelioid cells are cuboidal cells forming tubular or papillary structures. The gold standard is electron microscopy, which demonstrates long microvilli and abundant tonofilaments. Tissue stains are also helpful.
Present with chest pain, dyspnoea and recurrent pleural effusion. Asbestosis is present in 20%.
Metastases are to lymph nodes, and liver / distant organs as a late complication. Local invasion of lung and chest wall is common.
Aggressive therapy (extrapleural pneumonectomy, chemotherapy and radiotherapy) may improve prognosis in some patients.
50% 1-year mortality. Few survive 2 year
Definition: Diffuse pulmonary disease characterised by increased resistance to airflow from partial or complete obstruction of airways.

(cf: restrictive pulmonary diseases characterised by reduced pulmonary compliance and total lung capacity – from chest wall disorders or interstitial lung disease which may be acute or chronic)


Emphysema; Chronic Bronchitis; Asthma; Bronchiectasis.


Anatomic airway obstruction – asthma; bronchitis; bronchiectasis
Loss of elastic recoil - emphysema
Other lung neoplasms
Classification: carcinoid, hamartoma, metastases

Carcinoid: - slow growing neuroendocrine tumour, that may arise in the lungs from neuroepithelial bodies in the lung parenchyma

Epidemiology: - 1-5% of all lung tumours
- 90% of all bronchial adenomas
- M:F 1:1
- majority are <40 years

Pathogenesis: - arise from the neuroendocrine cells and belong to the APUDomas - amine precursor uptake and decarboxylation cells
(Kulchitsky cells of the bronchial mucosa)
- although multiple products may be synthesized by a single tumour, most secrete a predominant product to produce a clinical syndrome called by that name
- Serotonin - 5-hydroxy tryptamine - Carcinoid Syndrome most common
-there is no known relationship to cigarette smoking or other environmental factors. Occasionally associated with MEN I.

Macroscopic Pathology:
- polypoid tumour with a spherical or finger-like shape that commonly project into the lumen of a bronchus
- usually covered by an intact mucosa
- highly vascular

microscopic pathology:
- nests, cords and rosettes of uniform small round cells, separated by a delicate fibrous stroma
- tumour cells are monotonously similar
- the cytoplasmic granules are capable of reducing silver nitrate (argentaffin granules)

Clinical Presentation:
- intraluminal growth produces the following symptoms
- cough, haemoptysis, infections, bronchiectasis, atelectasis, air trapping

- Carcinoid Syndrome
- in 1% of patients with carcinoid
- in 20% of those with widespread mets
- 5HT is degraded in the liver to functionally inactive 5-HIAA
-episodic flushing, diarrhoea, bronchospasm
- Other Syndromes eg cushings

Management: - surgery
- metastases go to liver, lymph nodes, lung and bone (osteoblastic mets) uncommon

Prognosis: - overall 5-10 year survival for bronchial carcinoids is 50-90%
- <10% are atypical carcinoids - showing cytological atypia, necrosis and aggressive behaviour - these have a 50% recurrence rate after 2 years



- developmental malformation consisting of neoplastic like benign overgrowth of tissues proper to the part, appearing at birth or soon after, and generally ceasing when body growth stops


- Peripheral 90%
- Central 10%
- Single
- Multiple (rare)


- most common benign mass, M:F 3:1


- rarely seen in children
- usually seen 40-60years

Macroscopic Pathology

- rarely >3-4cm diameter
- spherical/slightly lobulated
- normal surrounding lung
- may have calcification (linear, speckled)
- calcification increases with lesion size
- cartilaginous calcification is virtually diagnostic
- appearance depends on tissue composition (see below)

Microscopic Pathology

- may be mixture of fibrous tissue, fat, blood, vessels, lymphoid tissue, bronchial like structures and cartilag
- spaces may be lined by respiratory epithelium


- usually asymptomatic and detected on CxR
- very slow growing
- may cause airway obstruction (see below)


- good
- only problems are due to localised mass effect.
- no malignant potential

lung metastases:
-commoner than primary lung cancers 90% >50yrs more in increasing age
-usually haematogenous spread but can also be direct eg mediastinal or oesophageal
-primary, lymphatics eg lymphoma
- origin breast 22%, renal 11% , H&N 10%, colorectal 9%
-morphology patterns
1) solitary mass 25%
2) multiple nodules including miliary subtype.
3) lymphangitis carcinamatosis
Lung disease secondary to occupational exposure to inorganic or organic dusts, or chemical fumes.
Pneumoconioses are classified according to the disease-causing agent: Inorganic dust diseases include silicosis, coal-worker's pneumoconiosis and asbestosis. Organic dusts diseases include farmer's lung (mouldy hay) and asthma due to Western Red Cedar dust. Chemical fume diseases include hypersensitivity and direct toxic effects of sulphur dioxide, ammonia and benzene.
Occur in workers exposed to the disease-causing agent. Silicosis is the most prevalent chronic occupational disease. Asbestos-related mesothelioma can occur in family members.
CWP is caused by coal dust. If silica is present also, the disease is worse. Silicosis is due to silica (amorphous or crystalline), with crystalline being more fibrogenic. The mixture of other minerals such as iron (haematite) is thought to be protective.
Asbestos-related disease is due to asbestos fibres (a crystalline form of silica) . Asbestos may be serpentine or amphibole in fibre form, with amphibole (straight, stiff fibres) forms being more toxic.
Particle size, shape and solubility is important in pathogenesis. The most dangerous particles are 1-5 microns diameter (these reach the terminal airways and alveoli). Injury is due to direct toxic effect, free radical formation, and macrophage activation with subsequent chronic inflammatory response. Smoking exacerbates the effects (partly by inhibiting mucociliary clearance). The effects of asbestos are particularly magnified by smoking - this may be partly due to adsorbtion of tobacco toxins onto asbestos fibres.
Macroscopic Pathology:
CWP: Disease ranges from asymptomatic anthracosis (characterised by anthracotic pigment in pulmonary lymphatics and lymph nodes) to simple CWP (coal macules 1-2mm diameter, and larger coal nodules). Upper zones more affected. Complicated CWP (progressive massive fibrosis) is characterised by black scars >2cm diameter, again in the upper zones. Silicosis: Discrete nodules in the upper zones, which tend to coalesce to hard, collagenous scars. Central cavitation may occur (NB increased incidence of TB). Fibrosis and calcification occurs in hilar & mediastinal lymph nodes. PMF also occurs. Asbestosis: Diffuse pulmonary fibrosis progresses to honeycombing, beginning in the lower zones, with a pattern similar to UIP. Pleural plaques of dense collagen +/- calcium on the parietal pleura only. Occasional pleural effusions.
Microscopic Pathology:
CWP: Nodules consist of carbon-laden macrophages in a delicate network of collagen. Silicosis nodules consist of a dense, lamellated collagen matrix, with birefringent silica particles within. Asbestosis is characterised by the presence of asbestos bodies, which are asbestos fibres with adsorbed brown iron-containing proteinaceous material. Fibrous tissue distorts the normal alveoli and thickens the interstitium.
Clinical Presentation:
The chronic pneumoconioses present with cough and progressive dyspnoea, which may lead to respiratory failure, cor pulmonale and death. The acute pneumoconioses may present with asthma, hypersensitivity pneumonitis, ARDS or pulmonary oedema.
Progressive massive fibrosis may complicate CWP or silicosis. It may be progressive despite cessation of exposure. PMF typically leads to respiratory failure, pulmonary hypertension and cor pulmonale. Silicosis may be associated with an increased incidence of lung carcinoma but this is controversial. Asbestos exposure is associated with a marked increase in the incidence of lung carcinoma, especially if combined with smoking (55x). The incidence of mesothelioma is >1000x, with no smoking link.
Other than limitation of exposure to the offending agent, and cessation of smoking, management is largely symptomatic.
Simple CWP is generally relatively benign. Silicosis tends to be more progressive, and although slow to kill, may cause significant morbidity. Asbestosis may also be associated with high morbidity, and with lung carcinoma or mesothelioma development, prognosis is poor.
Primary Atypical Pneumonia
Definition: An acute infectious pneumonia due to a variety of organisms especially viruses and Mycoplasma which is characterized by patchy inflammatory changes mainly localized to the pulmonary interstitium (alveolar septum)
and lacking in alveolar exudate.

Epidemiology: Mycoplasma pneumoniae (most common cause)


Pathogenesis: Pathogens:
1) Viral: influenza A / B, RSV, adenovirus, varicella
2) Mycoplasma: Mycoplasma pneumoniae
3) Protozoal: PCP

Macroscopic Pathology: All causal agents produce a similar morphological pattern

Lung: Site 1) distribution variable uni/bilateral, patchy, no obvious consolidation

Pleura: Usually normal effusions and pleuritis infrequent

Microscopic Pathology: Changes similar to ARDS
1) alveoli normal early
2) localized to interstitium mainly
3) Mononuclear inflammatory cells
4) Alveoli variable involvement including: necrosis, viral inclusions, viral cytopathy, hyaline membranes (characteristic pink membranes lining alveoli reflect alveoli wall damage), alveolar consolidation, bacterial superinfection
5) Resolution (common)

Clinical Presentation: Cough, fever, chest pain

Management: Supportive therapy Bactrim PCP prophylaxis

Prognosis: Depends on cause
Pulmonary Infections
Definition: Bacterial Infection of the lung parenchyma resulting in pulmonary consolidation (exudative solidification)

Classification: There is anatomical overlap:
1) lobar pneumonia
2) Bronchopneumonia
3) Interstitial pneumonia

Epidemiology: Different populations are susceptible to various infections. Examples hospital acquired pneumonia, alcoholics, immune compromised etc

Aetiology: include associations, risk factors pulmonary infections occur when lung or systemic defences are impaired. Pulmonary defences include nasal, tracheobronchial and alveolar mechanism to filtrate, neutralize and clear inhaled organisms and particles.

Pathogenesis: Cough refelex, mucociliary clearance, decrease in alveolar macrophage activity, edema, secretions and congestion and defects in innate or specific immunity.
Idiopathic systemic disease characterised by noncaseating granulomas in many tissues and organs.
Type I: hilar / mediastinal lymphadenopathy only. Type II: lymphadenopathy + lung disease. Type III: lung disease only.
Chest pathology is present in 90% of cases. More common in women than men. Rare in Asians.
Aetiology / Pathogenesis
Probably a disease of disordered immune regulation in genetically predisposed individuals, exposed to certain environmental agents. Immune changes: oligoclonal expansion of CD4+ T cell subsets, increased TH1 and macrophage cytokines. There is anergy to common skin test antigens, and polyclonal hypergammaglobulinaemia. Genetic predisposition: familial / racial clusters; association with HLA-A1 and B8. Environmental factors: Possibly microbes, but no evidence to date.
All involved tissues show noncaseating granulomas. Almost all tissues may be involved. Nodules occur in the lungs, primarily along lymphatics. Healing produces fibrosis. Lymph nodes and tonsils are commonly involved. Skin and eyes are also commonly involved. Lacrimal gland and salivary gland involvement -> Mikulicz syndrome. Spleen, liver, bone marrow, muscle, heart, kidneys, CNS and pituitary are often involved.
Epithelioid cells and giant cells combine to form noncaseating granulomas. Schaumann bodies (laminated concretions of calcium and protein) and asteroid bodies (stellate inclusions in giant cells) are often seen and are characteristic but not pathognomonic.
May be asymptomatic, or may present with lymphadenopathy, cutaneous lesions, eye involvement, splenomegaly or respiratory impairment (most common). May be chronically progressive, or relapsing & remitting.
Blindness from corneal ulceration or uveitis. Respiratory failure or cor pulmonale. CNS or cardiac impairment.
Steroids may induce remission.
65-70% recover with minimal residual impairment. 20% have permanent loss of respiratory or eye function. 10-15% die of respiratory, cardiac or CNS disease. The best prognosis in in type I. Type III disease is unlikely to remit.
Definition: Chronic infective disease caused by infection with mycobacterium tuberculosis

• Primary TB – infection from exogenous source in previously unexposed, unsensitised person
• Secondary TB – pattern of disease in previously sensitised person. May arise from (1) reactivation of latent lesions when host resistance weakens, or (2) from exogenous reinfection because of waning protection or large inoculum of virulent bacilli.
• Miliary pulmonary TB - lympho/haematogenous dissemination of primary/secondary TB
• Extrapulmonary (15%): Systemic miliary TB, Isolated organ TB, TB meningitis, Lymphadenitis (scrofula), Intestinal TB

Affects 1.7 billion people worldwide. 9 million new cases a year. 1.7 million deaths/yr
M>F. Age peak 50-60
Associations / Risk factors in developed countries:
Migrants, poverty, crowding, chronic debilitating illness, diabetes, Hodgkins, chronic lung disease (esp silicosis), chronic renal failure, malnutrition, alcoholism, immunosuppression (eg HIV)

Aetiology: M. tuberculosis infection. (Ingestion of M. bovis in milk causing intestinal TB now less common)

Usually person-to-person transmission of M. tuberculosis in airborne droplets.
M. tuberculosis endocytosed by macrophages  replicates within phagosome of macrophage.  After 3 weeks, TH1 response mounted (Type 4 cell-mediated Immune response)  stimulates macrophages to kill mycobacteria, form granulomas and caseous necrosis

Macroscopic Pathology:
• Primary TB – 1-1.5cm grey-white consolidation in lower part of upper lobe or upper part of lower lobe (Ghon focus), which develops caseous necrosis. Regional node involvement and caseation. Ghon complex = Ghon focus + LN.
• Non progressive Primary TB - sequelae in 95%. Latent lesions. Contraction, fibrosis & calcification of Ghon complex = Ranke complex
• Progressive Primary TB – rare sequelae. Lower and middle lobe consolidation, lymphadenopathy, pleural effusion, spread
• Secondary TB – Simon focus = <2cm focus of circumscribed, firm, grey-white consolidation in upper lobe apex <2cm from pleura (High oxygen tension in apices promotes bacterial growth). Variable central caseation and peripheral fibrosis
• If favourable, develop minor caseation, then fibrocalcific scarring (Arrested fibrocalcific TB)
• Progressive Secondary TB – in elderly and immunosuppressed. Includes
• Cavitary Fibrocaseous TB (Localised cavitary destructive lesions) – apical cavity formed by erosion into airway, yellow-green caseous materal, fibrous wall. May erode blood vessels.
• Other patterns of Progressive Pulmonary TB:
• Endobronchial, endotracheal and laryngeal tuberculosis
• Miliary TB –
• Pulmonary - microscopic or small visible <2mm scattered yellow-white foci of consolidation
• Extrapulmonary – kidney, adrenal, spleen, LN, Bmarrow, meninges, prostate, seminal vesicles, fallopian tubes
• Tuberculous bronchopneumonia “galloping consumption” – in susceptible individuals. extensive diffuse consolidation. Well-defined tubercles don’t form.
• Pleural involvement – serous effusions, empyema, obliterative fibrous pleuritis. Empyema – caseous necrosis, fibrosis and calcification.

Microscopic Pathology:
In immunocompetent: After 3 weeks, granulomatous inflammatory reaction forming caseating and non-caseating tubercles. Pattern: 1. Central caseous necrosis (combination of coagulative and liquefactive necrosis). 2. Epitheloid cells + Langhans giant cells. 3. Peripheral rim of lymphocytes & fibroblasts
In immunocompromised: Characteristic granulomas do not form

Clinical Presentation:
May be asymptomatic
Primary infections - 5% have clinically significant disease fever, pleural effusion
Secondary infections – insidious onset
Fever, commonly low grade and remittent. Night sweats.
Sputum mucoid becoming purulent. Haemoptysis in 50%
Pleuritic pain.

Bronchopleural fistula, empyema
Fibrosing mediastinitis
Endobronchial dissemination from cavitation to other segments
Cavity colonisation with aspergillus (aspergilloma) or bacteria
Systemic miliary TB

Management: Antibiotics RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol). Previously plombage with plastic packs, Lucite balls, polythene spheres, oleothorax

Prognosis: Cure or arrest of active disease is usual, unless severe immunocompromised
Wegener Granulomatosis

- rare form of necrotising vasculitis characterized by the triad of upper respiratory tract, pulmonary and renal involvement


- M>F
- peak incidence in the 5th decade

Aetiology & Pathogenesis:

- thought to represent some form of hypersensitivity possibly to an inhaled infectious agent or other environmental factor
- dramatic response to cyclophosphamide suggests an immunologic mechanism
- C-ANCA is found in 93% of patients with active generalised disease

Macroscopic Pathology:

- the vasculitis affects small arteries and veins and may be seen in vitually any organ of the body
- Classical Feaures are:
- acute necrotising granulomas of the upper and lower respiratory tract
- nose, ears, sinuses, throat and lung
- focal necrotising vasculitis, most prominent in the lungs and upper airways
- affecting small to medium-sized vessels
- granulomas may undergo progressive fibrosis and cavitation
- renal disease is in the form of focal or diffuse necrotising glomerulonephritis

Microscopic Pathology:

- areas of focal acute necrosis are seen throughout the respiratory tract
- In addition, focal granulomas are seen scattered throughout the lung parenchyma
- these lesions show central necrosis surrounded by:
- lymphocytes, plasma cells, macrophages and a variable number of giant cells
- there is also a necrotising or granulomatous vasculitis
- may be associated with or clearly separated from vessel walls
- these areas are surrounded by a zone of fibroblastic proliferation containing:
- giant cells and leukocytic infiltrate
- may resemble a tubercle
- lesions may eventually undergo progressive fibrosis and organisation
- the renal lesions are of two types
- focal necrotising glomerulonephritis
- a more diffuse crescentic form of glomerulonephritis


- persistent pneumonitis
- chronic sinusitis
- evidence of renal disease
- Limited Form of W.G.
- some patients do not manifest the renal component
- disease is restricted to the respiratory tract


- untreated course is malignant and 80% die within one year
- with treatment, up to 90% respond, with only occasional relapses.
- C-ANCA is a good activity marker
⬢ Acute (days to weeks): Acute Interstitial Pneumonia
⬢ Sub-acute (<3/12):
1. Desquamative interstitial pneumonia
2. Cryptogenic organising pneumonia
⬢ Chronic (>3/12):
1. Usual interstitial pneumonia
2. Nonspecific interstitial pneumonia
3. Lymphoid interstitial pneumonia
4. Respiratory bronchiolitis associated interstitial lung disease
Definition: chronic interstitial pneumonia of unknown cause characterised by histopathologic pattern of usual interstitial pneumonia


Epidemiology: 50-70 yo. M>F. Commonest idiopathic interstitial pneumonia

Aetiology: Unknown causative agent. Majority are smokers but role not clarified
(Drugs eg. Bleomycin, cyclophosphamide and busulfan and Scleroderma can produce similar pattern)

Pathogenesis: “Repeated cycles” of acute lung injury (alveolitis) by some unidentified agent. “Wound healing” at these sites gives rise to exuberant fibroblastic proliferation, giving rise to “fibroblastic foci”

Macroscopic Pathology: Pleural surfaces cobblestoned due to retraction of scars along interlobular septa. Firm, rubbery white areas of fibrosis seen on cut surface with lower lobe predominance, in subpleural distribution and along interlobular septa

Microscopic Pathology: Patchy interstitial fibrosis, varying in intensity and with time (Temporal and spatial heterogeneity). Both early (fibroblastic proliferations) and late lesions (more collagenous, less cellular) coexist. Smooth muscle hyperplasia. Honeycomb fibrosis = dense fibrosis causing collapse of alveolar walls and formation of cystic spaces

Clinical Presentation: Chronic insidious, gradually increasing dyspnea on exertion and dry cough. Hypoxemia, cyanosis and clubbing late.

• Respiratory failure, Pulmonary hypertension & Cor pulmonale,
• 10-15% Increased incidence of lung cancer, predominantly lower lobes
• opportunistic infection
• rapid deterioration

Management: Lung transplant only definitive therapy. Steroids, interferon, azathioprine
Prognosis: Unpredictable progression. Gradual or rapid deterioration. Mean survival 3 years or less.
Definition: Interstitial lung disease of unknown aetiology which on lung biopsy shows no diagnostic features of other well-characterized interstitial diseases.

Classification: Two histologic patterns: 1. Cellular pattern 2. Fibrosing pattern

Epidemiology: 46-55 yo. Those with cellular pattern younger than those with fibrosing pattern. F>M. 2nd most common after IPF

Aetiology: Unknown

Macroscopic Pathology: Bilateral basal & symmetrical, subpleural. Honeycombing and consolidation infrequent
Microscopic Pathology:
1. Cellular pattern – chronic interstitial inflammation containing lymphocytes, few plasma cells
2. Fibrosing pattern – diffuse or patchy interstiial fibrosis with temporal homogeneity
No fibroblastic foci

Clinical Presentation: Chronic Dyspnoea and cough for several months


Prognosis: much better prognosis than IPF. Cellular pattern better outcome
Definition: Rare interstitial pneumonia characterised by interstitial lymphocytic infiltrate

Epidemiology: F>M. 40-50yo. Very rare. Rarest of the idiopathic interstitial pneumonias

Aetiology/ Associations: collagen vascular diseases, Sjogrens, immunodeficiency, rarely idiopathic

Macroscopic Pathology: subpleural and peribronchovascular nodules and septal lines. Perivascular cysts occasionally
Microscopic Pathology: diffuse lymphocyte interstitial infiltrate, predominantly alveolar septal distribution

Clinical Presentation: Chronic slow onset dyspnoea, cough, fever, weight loss, arthralgia. Signs/symptoms of underlying disease

Management: steroids

Prognosis: rarely progresses to fibrosis
Definition: clinicopathologic syndrome of unknown aetiology characterised histologically by polypoid plugs of connective tissue within small airways

Epidemiology: middle aged females. Mean age 55

Aetiology / Associations:
Idiopathic type most common - Unknown aetiology
(Same pattern seen as a response to infections or inflammatory injury of lungs eg. Viral/bacterial pneumonia, inhaled toxins, drugs, collagen vascular disease, graft versus host disease in bone marrow transplant patients, bronchial obstruction – not called COP)

Macroscopic Pathology:
(1) Diffuse centrilobular nodules – consolidation. Patchy peribronchial or peripheral in lower zones
Or (2) Focal mass-like consolidation.

Microscopic Pathology:
1. Early phase: localised lesion centering on a bronchiole. Lymphocytes and plasma cells in fibrous tuft in airway. Temporal homogeneity. Mild chronic inflammatory infiltrate
2. Late phase : branching polypoid plugs of fibrous connective tissue within alveolar ducts and alveoli, and often bronchioles. Underlying lung architecture normal. Interstitial fibrosis

Clinical Presentation: Subacute productive cough, dyspnoea, weight loss, fever, myalgia. Pneumonia unresponsive to antibiotics.

Management: Oral steroids for 6 months or longer

Prognosis: some recover spontaneously but most require steroids for complete recovery. Relapse may occur. (When associated with underlying condition, prognosis same as for underlying disorder).

Definition: form of interstitial pneumonitis occuring in smokers characterised by accumulation of pigmented macrophages in alveoli

Epidemiology: 30-40 yo. M>F 2:1

Aetiology/ Associations / Risk factors: Virtually all patients are smokers

Macroscopic Pathology: lower zone & peripheral predominance

Microscopic Pathology: accumulation of macrophages with abundant cytoplasm containing dusty brown pigment (smokers macrophages) in alveoli. Thickening of alveolar septa by sparse infiltrate of lymphocytes. Spatial homogeneity. Chronic inflammatory infiltrate. Minimal fibrosis. Honeycombing uncommon

Clinical Presentation: Subacute insidious slow onset dyspnoea, dry cough, clubbing

Management: Steroids (excellent response). Smoking cessation

Prognosis: Good. Non progressive in vast majority. 100% survival

Definition: Clinical manifestation of interstitial lung disease associated with pathologic lesion of respiratory bronchiolitis

Epidemiology: 30-40 yo >30 pack years of smoking. M>F 2:1

Aetiology: Associations / Risk factors

Macroscopic Pathology: centrilobular emphysema, centrilobular nodules. Upper lobe predominance

Microscopic Pathology: bronchiolocentric accumulation of alveolar macrophages with pigment. Mild patchy submucosal and peribronchiolar infiltrate of lymphocytes and histiocytes. Mild peribronchiolar fibrosis.

Clinical Presentation: chronic mild cough, dyspnoea

Management: Smoking cessation

Prognosis: smoking cessation usually results in improvement

Definition: spectrum of immunologically mediated, predominantly interstitial, lung disorders caused by prolonged exposure to inhaled organic dusts acting as antigens. ?Characterised by mononuclear interstitial pneumonitis progressing to fibrosis.

Acute EAA – heavy acute exposure
Subacute EAA – less intense but continuous exposure
Chronic EAA – prolonged exposure, presenting months to years later


Aetiology/ Associations / Risk factors: Organic dust containing antigens eg. Spores of thermophilic bacteria, fungi, animal proteins, bacterial products

Pathogenesis: Type III (immune complex) hypersensitivity and Type IV (delayed type) hypersensitivity

Macroscopic Pathology:
1. Acute EAA – consolidation early +/- lymphadenopathy
2. Subacute-Chronic EAA - firm lung, distorted lung architecture, honeycombing

Microscopic Pathology:

In subacute and chronic forms disease centred on bronchioles
Interstitial pneumonitis
Noncaseating granulomas
Intralveolar infiltrates seen in 50%.
Interstitial fibrosis and obliterative bronchiolitis in late stages.

Clinical Presentation:
Acute attacks 4-6 hours following inhalation of antigenic dust – fever, dyspnoea, cough, leukocytosis
Chronic form – progressive respiratory failure, dyspnoea, cyanosis, restrictive lung pattern



Prognosis: can progress to serious chronic fibrotic lung disease without removal of the environmental agent

Definition: Clinical manifestation of interstitial lung disease associated with pathologic lesion of respiratory bronchiolitis

Epidemiology: 30-40 yo >30 pack years of smoking. M>F 2:1

Aetiology: Associations / Risk factors

Macroscopic Pathology: centrilobular emphysema, centrilobular nodules. Upper lobe predominance

Microscopic Pathology: bronchiolocentric accumulation of alveolar macrophages with pigment. Mild patchy submucosal and peribronchiolar infiltrate of lymphocytes and histiocytes. Mild peribronchiolar fibrosis.

Clinical Presentation: chronic mild cough, dyspnoea

Management: Smoking cessation

Prognosis: smoking cessation usually results in improvement
Definition: clinicopathologic syndrome of unknown aetiology demonstrating widespread acute lung injury with rapidly progressive clinical course, resembling ARDS

Epidemiology: wide age range. mean age 50 years. M=F

Aetiology / Pathogenesis : Unknown

Macroscopic Pathology:
Acute phase - Identical appearance to ARDS. Heavy, firm, red, boggy lungs. Diffuse consolidation
Late phase – fibrosis, architectural distortion, cysts, traction bronchiectasis

Microscopic Pathology: Identical appearance to ARDS.
1. Exudative phase - Congestion, interstitial and intra-alveolar oedema, inflammation and fibrin deposition. Temporal homogeneity. Alveolar walls lined with waxy hyaline membranes.
2. Organizing phase – organizing fibrin, loose organising fibrosis in alveolar lumens

Clinical Presentation: Acute respiratory failure often following an illness of less than 3 weeks’ duration resembling URTI

Complications: chronic interstitial disease

Management: Lung transplant only definitive therapy

Prognosis: Mortality rate 50%, most deaths in 1-2 months. Survivors may develop recurrences and chronic interstitial disease.
Definition: pulmonary involvement during the course of a collagen vascular disease

Classification: by patterns: NSIP pattern, UIP pattern, vascular sclerosis, organizing pneumonia, bronchiolitis

Epidemiology: as for underlying diseases
1. Scleroderma – M<F 1:3. 50-60 yo. Lungs involved in >50%
2. SLE – M<F 1:10. 20-40 yo.
3. RA – M<F 1:4. 20-50 yo but M>>F develop rheumatoid lung

Aetiology / Associations: collagen vascular diseases including SLE, RA, scleroderma, dermatomyositis/polymyositis, mixed connective tissue disease


Macroscopic Pathology / Microscopic Pathology:

1. Scleroderma – Bilateral lower lobe fibrosis, peripheral. NSIP more than UIP pattern. Honeycombing. Alveolar changes ? aspiration related. Variable fibrous thickening of small pulmonary vessels

2. SLE - Pleural disease, pleuritis in 45%
Lupus pneumonitis in 10% - patchy bilateral alveolar consolidation, oedema, haemorrhage
Chronic interstitial fibrosis in 3% - bilateral lower lobes, peripheral

3. RA 1. Chronic pleuritis. Pleural effusions in 3%, usually unilateral. Bilateral pleural thickening
2. DIP pattern and fibrosis – bilateral basal, peripheral
3. Intrapulmonary rheumatoid nodules – rare only in advanced RA. 0.3-7cm well circumsribed nodules +/- cavitation. Usually multiple, often peripheral
Micro: (1) central fibrinoid necrosis, surrounded by (2) peripheral epitheloid histiocytes, lymphocytes, (3) fibrosis
4. Pulmonary hypertension – due to pulmonary arteritis affecting small and medium sized arteries. Micro: fibroelastoid intimal proliferation
5. Caplan syndrome = coexistence of RA and a pneumoconiosis leading to development of distinctive nodular pulmonary lesions 0.5-5cm. Mainly peripheral upper lobes. Micro similar to rheumatoid nodules

Clinical Presentation:




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