Preclinical Pathology

🧬 Congenital lung malformations

Congenital pulmonary airway malformation (CPAM)
- Developmental defect of parenchyma; communicates with tracheobronchial tree.
- Gross: single large cyst (3‑10 cm) → multiple small cysts → solid mass.
- Prenatal US diagnosis; rarely asymptomatic until adulthood.
- Symptomatic (recurrent infection, pneumothorax) → surgical resection.
- Severe hydrops / mediastinal shift → prenatal surgery.
Bronchopulmonary sequestration
- Non‑communicating mass of pulmonary tissue.
- Intralobar: pulmonary artery supply; extralobar: descending aorta supply.
- Most regress spontaneously; some remain undiagnosed into adulthood.
- Pleural effusion may require intrauterine treatment.

Reversible lung collapse / nonexpansion → predisposes to infection (impaired mucociliary clearance).
Obstruction/resorption: air resorption distal to obstruction (foreign body, COPD, post‑op).
Compression: fluid, air, blood, or tumor in pleural space.
Contraction (scar): fibrosis / scarring of lung parenchyma.
Patchy: surfactant deficiency (hyaline membrane disease, ARDS).

Surfactant deficiency → patchy atelectasis in neonates and ARDS.

Lobar pneumonia – entire lobe consolidation.
- Typical: Streptococcus pneumoniae (95%) or Klebsiella.
- Phases: congestion → red hepatization → gray hepatization → resolution (rarely seen today).
- Alpha‑hemolytic, bile soluble, optochin sensitive.
Bronchopneumonia – patchy, bilateral, basilar, centered on bronchioles.
- Organisms: Staphylococcus, Strep, H. influenzae, Pseudomonas.
- Susceptible: young, elderly, terminally ill.
Lung abscess – localized pus + necrotic parenchyma.
- Most common: aspiration (right lower lobe, mixed oral flora).
- Also: post‑pneumonia (S. aureus, Klebsiella), post‑obstructive, septic emboli.
- Complications: empyema, hemorrhage, secondary amyloidosis.
Atypical pneumonia – interstitial pneumonitis, no consolidation.
- Young adults/children; Mycoplasma, viruses (RSV, CMV, influenza).
- CXR: diffuse interstitial infiltrates. Cold agglutinins → Mycoplasma.
- Complications: superinfection, Reye syndrome (aspirin + viral illness).

Empiric antibiotics → adjust per culture/sensitivities. Always consider atypical coverage.

Tuberculosis – aerosolized bacilli.
- Primary: Ghon focus (subpleural caseous granuloma) + hilar nodes = Ghon complex. 95% fibrose/calcify.
- Secondary (reactivation): apical Simon focus (high O₂). AFB‑positive caseating granulomas.
- Miliary dissemination: meninges, cervical nodes, liver, bone (Pott), adrenals, ileum, fallopian tubes.
- M. avium complex (MAC): AIDS (CD4 <50) – disseminated.
Sarcoidosis – systemic noncaseating granulomas (unknown etiology).
- Most common: African American women, age 20‑60.
- Bilateral hilar adenopathy on CXR; elevated ACE.
- Biopsy: noncaseating granulomas, Schaumann bodies, asteroid bodies.
- Prognosis: variable; most recover, some progress to respiratory failure.

Sarcoidosis is a diagnosis of exclusion – no pathognomonic feature.

Chronic bronchitis – cough + sputum ≥3 months/2 years.
- 90% smoking; Reid index >0.4 (gland hyperplasia).
- Complications: recurrent infections, cor pulmonale, lung cancer.
Emphysema – septal destruction, enlarged air spaces, loss of elastic recoil.
- Centrilobular (smoking) – proximal acinus.
- Panacinar (α‑1 antitrypsin deficiency) – entire acinus.
- Distal acinar – pleura → pneumothorax.
- Irregular – post‑inflammatory scarring.
Asthma – hyperreactive airways, episodic bronchospasm.
- Atopic (IgE), nonatopic (infections/stress), drug‑induced (aspirin), occupational.
- Sputum: Curschmann spirals, eosinophils, Charcot‑Leyden crystals.
- Autopsy: mucous plugs, goblet cell hyperplasia, smooth muscle hypertrophy, thickened basement membrane.
Bronchiectasis – permanent airway dilatation from chronic necrotizing inflammation.
- Causes: obstruction, necrotizing pneumonia, cystic fibrosis, Kartagener (dynein defect, situs inversus).
- Complications: abscess, septic emboli, cor pulmonale, amyloidosis.

ARDS (DAD) – diffuse alveolar/capillary damage, progressive hypoxemia.
- Causes: shock, sepsis, trauma, aspiration, radiation, drugs.
- Path: heavy, stiff lungs; hyaline membranes; type II pneumocyte proliferation.
- Mortality ~40%.
Neonatal RDS – surfactant deficiency (prematurity, maternal diabetes, C‑section).
- CXR: ground‑glass reticulogranular densities; hyaline membranes.
- Treatment: surfactant, mechanical ventilation, CPAP; corticosteroids if preterm.
Chronic interstitial
- IPF (usual interstitial pneumonia) – honeycomb fibrosis, fatal.
- Nonspecific interstitial pneumonia – better prognosis.
- Cryptogenic organizing pneumonia – responds to steroids.
- Collagen vascular disease – poor prognosis.
- Smoking‑related: desquamative interstitial pneumonia, respiratory bronchiolitis, fibrosis.
Occupational
- Coal worker’s: simple (black lung) → complicated (progressive massive fibrosis).
- Asbestosis: diffuse fibrosis (lower lobes); asbestos bodies (ferruginous); pleural plaques; ↑ lung cancer & mesothelioma (synergy with smoking).
- Silicosis: upper lobe nodular fibrosis; ↑ TB risk.
- Berylliosis: granulomatous (type IV hypersensitivity).

Aspiration→ Chemical pneumonitis→ ARDS/DAD→ Hyaline membranes

Pulmonary edema – Starling imbalance / endothelial injury.
- ↑ hydrostatic: left heart failure, mitral stenosis, fluid overload.
- ↓ oncotic: nephrotic, liver disease.
- ↑ permeability: infection, drugs (bleomycin, heroin), shock.
- Path: heavy lower lobes, intra‑alveolar fluid, hemosiderin‑laden macrophages (heart‑failure cells).
Pulmonary hypertension – ↑ pulmonary artery pressure.
- Causes: COPD, interstitial disease, recurrent PE, mitral stenosis, left‑to‑right shunts.
- Path: medial hypertrophy, intimal fibrosis, plexogenic arteriopathy → cor pulmonale.
Lung cancer – leading cancer death.
- Adenocarcinoma: peripheral, scar carcinoma, women/nonsmokers. Precursor: AAH → AIS → minimally invasive.
- Squamous: central, smoking, metaplasia → dysplasia → CIS → invasive. Keratin pearls.
- Small cell: aggressive, neuroendocrine, paraneoplastic. Crush artifact, dense‑core granules.
- Large cell: anaplastic, no differentiation.
Carcinoid – younger age, polypoid intrabronchial, organoid nests, neurosecretory granules.
Metastatic – most common lung malignancy; multiple bilateral nodules.
Hamartoma – benign coin lesion, fibromyxoid tissue; Carney triad (chondroma, paraganglioma, GIST).

Horner syndrome (Pancoast): ptosis, miosis, anhidrosis, enophthalmos.

Pleural effusion
- Exudative: protein/serum >0.5, LDH/serum >0.6, LDH >⅔ upper normal. Causes: infection, malignancy, PE.
- Transudative: left ventricular failure, cirrhosis.
Hemothorax – blood (trauma); tracheal shift to unaffected side.
Chylothorax – lymphatic fluid (malignancy).
Pneumothorax – air in pleural space.
- Spontaneous: rupture of apical blebs (tall young adults).
- Tension: mediastinal shift, life‑threatening.
Mesothelioma – asbestos exposure (90%), biphasic pattern, poor prognosis.

Pleural plaques (asbestos) spare apices and costophrenic angles.