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PA25.7 | Lung Disease & Tumour Morphology — Practical — SDL Guide (Part 2)

Emphysema — Airspace Destruction

Four-panel medical diagram showing gross emphysematous lungs, microscopic alveolar septal destruction, centriacinar versus panacinar distribution, and elastase-alpha-1 antitrypsin pathophysiology. — **Panel A:** Gross emphysema: hyperinflated lung, failure to collapse, enlarged irregular airspaces, subpleural bullae, cut surface.. **Panel B:** Microscopy comparison: normal alveolar septa, emphysematous enlarged airspaces, loss of alveolar septa, capillary loss, mild chronic inflammation, no exudate or tumour.. **Panel C:** Disease patterns: centriacinar emphysema with upper-lobe predominance and respiratory bronchiole-centered enlargement; panacinar emphysema with lower-lobe predominance and uniform acinus destruction.. **Panel D:** Pathophysiology: tobacco smoke, activated neutrophils/macrophages, neutrophil elastase, elastin degradation, alpha-1 antitrypsin inhibition, alpha-1 antitrypsin deficiency..

Emphysema is a permanent, abnormal enlargement of airspaces distal to the terminal bronchiole with destruction of alveolar walls — the defining word is destruction, not just dilation.

Gross appearances:
• Hyperinflated, voluminous lungs that do not collapse on opening the chest.
• Cut surface shows enlarged, irregular airspaces; bullae (emphysematous blebs >1 cm, often subpleural) are visible to the naked eye.
• Centriacinar (centrilobular) emphysema — upper lobe predominance, associated with smoking; enlargement centred on respiratory bronchioles.
• Panacinar emphysema — lower lobe predominance, associated with α₁-antitrypsin deficiency; uniform destruction from respiratory bronchiole to alveolar sac.

Microscopic appearances:
• Loss of alveolar septa — 'holes in the tissue', fewer alveolar walls per high-power field than normal.
• Remaining walls show capillary loss and mild chronic inflammation.
• No exudate, no granuloma, no tumour — the key diagnostic feature is architectural loss, not filling.

Pathophysiology link: Neutrophil elastase (from tobacco-smoke-activated neutrophils/macrophages) degrades elastin in alveolar walls. α₁-antitrypsin normally inhibits this; its deficiency accelerates destruction.

Side-by-side low-power H&E comparison of normal lung with intact alveolar septa and emphysematous lung with enlarged airspaces, septal destruction, and bullae. — **Panel A:** Normal lung low-power H&E showing small regular alveoli, thin intact alveolar septa, and preserved alveolar network.. **Panel B:** Emphysematous lung low-power H&E showing enlarged airspaces, destroyed and reduced alveolar septa, fragmented septal remnants, and bulla formation..

SELF-CHECK

Which microscopic feature is MOST diagnostic of emphysema, distinguishing it from other causes of radiological hyperinflation?

A. Permanent loss and destruction of alveolar septa

B. Alveoli filled with neutrophilic exudate

C. Caseating granulomas in alveolar walls

D. Proliferation of type II pneumocytes lining intact alveoli

Reveal Answer

Answer: A. Permanent loss and destruction of alveolar septa

Emphysema is defined by permanent destructive enlargement of airspaces distal to the terminal bronchiole — alveolar wall destruction (septal loss) is the pathological hallmark. Neutrophilic exudate filling alveoli indicates pneumonia. Caseating granulomas indicate TB. Type II pneumocyte proliferation is a repair response (e.g., after diffuse alveolar damage) and does not feature septal destruction.

Pneumoconiosis — Dust-Induced Lung Disease

A three-panel comparison diagram of anthracosis, silicosis, and asbestosis showing gross lung changes, microscopic findings, and key exam points. — **Panel A:** Anthracosis / coal-worker's pneumoconiosis: black lung parenchyma, black hilar lymph nodes, anthracotic macules, anthracotic nodules, respiratory bronchiole, alveoli, carbon-laden macrophages, anthracotic pigment granules, no birefringence, no giant cells in simple CWP.. **Panel B:** Silicosis: upper-lobe white-grey silicotic nodules, progressive massive fibrosis, concentric laminated collagen whorls, birefringent silica particles under polarized light, surrounding macrophage reaction.. **Panel C:** Asbestosis: lower-lobe fibrosis, honeycombing, calcified pleural plaques with holly-leaf pattern, asbestos bodies, ferruginous bodies, golden-brown beaded rods, interstitial fibrosis, mesothelioma risk, lung adenocarcinoma risk..

Pneumoconiosis refers to lung diseases caused by inorganic dust inhalation. The three most testable types are:

1. Anthracosis (Coal-worker's pneumoconiosis)
• Gross: Black discolouration of lung parenchyma and hilar nodes; in simple CWP, anthracotic macules (1–2 mm black foci) and slightly larger anthracotic nodules around respiratory bronchioles.
• Micro: Collections of carbon-laden macrophages (anthracotic pigment = black granules) in respiratory bronchioles and surrounding alveoli. No birefringence. No giant cells in simple CWP.

2. Silicosis
• Gross: Multiple hard, white/grey silicotic nodules (2–5 mm, palpable) in upper lobes; in advanced disease nodules coalesce → progressive massive fibrosis.
• Micro: Concentric laminated collagen whorls with birefringent silica particles under polarised light at the centre. Surrounding macrophage reaction.

3. Asbestosis
• Gross: Lower lobe fibrosis (honeycombing), pleural plaques (white, calcified, 'holly-leaf' pattern).
• Micro: Asbestos bodies — golden-brown, dumbbell or beaded rod morphology (ferruginous bodies) formed by protein-iron coating on asbestos fibre. Background interstitial fibrosis.
• Carcinogenic: strongly associated with mesothelioma (pleural) and lung adenocarcinoma.

KEY EXAM POINT: Asbestos bodies = ferruginous bodies = golden-brown beaded rods on H&E. Silica nodules = laminated collagen whorls with birefringence.

CLINICAL PEARL

The latency period for asbestosis-related disease is long — mesothelioma may present 20–40 years after first exposure. When you see a pleural-based tumour in an older male with a history of shipbuilding, construction, or plumbing work, asbestos exposure tops the differential. Silicosis predisposes to secondary TB ('silicotuberculosis') — always check for concurrent granulomas in silicosis sections.

Lung Carcinoma — Histological Classification

A five-panel medical diagram compares the gross locations and microscopic hallmarks of small cell, squamous cell, adenocarcinoma, and large cell lung carcinoma. — **Panel A:** Lung silhouette with trachea, main bronchi, hilum, pleura, central/perihilar tumor zones, peripheral/subpleural tumor zones, and histology-guides-treatment note.. **Panel B:** Small Cell Lung Carcinoma showing small hyperchromatic cells, salt-and-pepper chromatin, scant cytoplasm, high N:C ratio, nuclear moulding, crush artefact, necrosis, mitoses, central bronchial mass, and neuroendocrine markers CD56, synaptophysin, chromogranin.. **Panel C:** Squamous Cell Carcinoma showing polygonal cells, keratin pearls, eosinophilic keratin center, intercellular bridges, individual cell keratinisation, and central cavitating hilar mass.. **Panel D:** Adenocarcinoma showing acinar glands, mucin production, papillary pattern, lepidic spread along intact alveolar walls, TTF-1 nuclear positivity, and peripheral subpleural mass.. **Panel E:** Large Cell Carcinoma showing large pleomorphic undifferentiated cells, abundant cytoplasm, prominent nucleoli, giant cells, necrosis, absence of glands or keratinisation, and peripheral bulky mass..

Lung carcinoma is classified primarily by histology because the type dictates treatment. The four main types and their microscopic hallmarks:

Small Cell Lung Carcinoma (SCLC)
• Micro: Sheets and clusters of small cells with:
- Hyperchromatic nuclei, coarsely granular ('salt-and-pepper') chromatin
- Scant cytoplasm — nuclear-to-cytoplasmic ratio is extremely high
- Nuclear moulding — nuclei conform to neighbours' shapes
- Crush artefact — nuclei smear in biopsy specimens (fragile cells)
- Necrosis common; mitoses abundant
• Gross: Central (perihilar) mass, bronchial origin, early mediastinal invasion
• Origin: Neuroendocrine (Kulchitsky cells); does NOT express TTF-1 in same pattern as ADC — immunostaining (CD56, synaptophysin, chromogranin) confirms

Squamous Cell Carcinoma (SCC)
• Micro: Sheets of polygonal cells with:
- Keratin pearls — concentric whorls of keratinising squamous cells, eosinophilic centre
- Intercellular bridges (desmosomes) between adjacent cells
- Individual cell keratinisation (bright pink cytoplasm)
• Gross: Central, hilar mass; may cavitate; often bronchial in origin

Adenocarcinoma
• Micro: Gland-forming structures and/or mucin production
- Acinar, papillary, micropapillary, lepidic patterns
- TTF-1 positive (nuclear)
• Gross: Peripheral mass, often subpleural; most common type in non-smokers and women
• Lepidic growth: tumour cells crawl along intact alveolar walls — 'spread along scaffolding'

Large Cell Carcinoma
• Diagnosis of exclusion: large anaplastic cells, no squamous/glandular/small-cell differentiation; requires IHC panel

Side-by-side H&E comparison of lung squamous cell carcinoma with keratin pearl and intercellular bridges, and lung adenocarcinoma with glandular lumina and mucin-containing cells. — **Panel A:** Squamous cell carcinoma showing malignant squamous nests, central keratin pearl highlighted by arrow, pleomorphic nuclei, eosinophilic cytoplasm, and inset showing intercellular bridges.. **Panel B:** Adenocarcinoma showing irregular malignant glands, glandular lumina, mucin-containing cells, pleomorphic nuclei, and surrounding desmoplastic stroma..

SELF-CHECK

A 52-year-old male heavy smoker presents with a central hilar mass. Biopsy shows small cells with scant cytoplasm, nuclear moulding, salt-and-pepper chromatin, and areas of crush artefact. The MOST likely diagnosis is:

A. Squamous cell carcinoma

B. Adenocarcinoma (lepidic pattern)

C. Small cell lung carcinoma

D. Carcinoid tumour

Reveal Answer

Answer: C. Small cell lung carcinoma

The combination of small hyperchromatic cells with scant cytoplasm, nuclear moulding, salt-and-pepper chromatin, and crush artefact is the classic SCLC picture. SCC shows keratin pearls and intercellular bridges. Adenocarcinoma shows gland formation and mucin. Carcinoid also has neuroendocrine features but cells are larger with more cytoplasm and absent crush artefact; carcinoid rarely shows moulding.