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PA25.7 | Lung Disease & Tumour Morphology — Practical — SDL Guide (Part 3)

Mesothelioma — The Pleural Rind

A four-panel medical diagram shows pleural mesothelioma as a thick white rind encasing the lung, its pleural spread pattern, histological subtypes, and key immunohistochemistry markers. — **Panel A:** Gross pleural mesothelioma with thick white pleural rind, compressed lung parenchyma, pleural cavity, lobulated tumour deposits, visceral pleura, parietal pleura, bloody pleural effusion.. **Panel B:** Cross-section showing mesothelioma spreading along pleural surfaces as a constrictive mantle, encased lung, pleural surface growth, minimal deep invasion, and progressive lung compression.. **Panel C:** Histology insets showing epithelioid pattern with tubules or papillae, sarcomatoid pattern with spindle cells and fibrous stroma, and biphasic pattern with mixed epithelioid and sarcomatoid areas.. **Panel D:** Immunohistochemistry comparison: mesothelioma calretinin positive, WT-1 positive, CK5/6 positive, CEA negative, TTF-1 negative; pulmonary adenocarcinoma CEA positive, TTF-1 positive, calretinin negative..

Mesothelioma is a primary tumour of mesothelial cells lining the pleura (rarely peritoneum or pericardium).

Gross: The classic appearance is a thick, white, rubbery pleural rind encasing the lung — the tumour envelops rather than invades; it grows along pleural surfaces forming a constrictive 'mantle'. Effusion is commonly bloody.

Micro: Three histological patterns:
• Epithelioid (most common, ~60%): Cuboidal/polygonal cells forming tubules, papillae, or solid sheets — can mimic adenocarcinoma (important distinction)
• Sarcomatoid: Spindle cells, fibrous stroma
• Biphasic: Mixed epithelioid + sarcomatoid

Key IHC panel (exam-level): Mesothelioma is calretinin+, WT-1+, CK5/6+, CEA−, TTF-1−. This separates it from pulmonary adenocarcinoma (CEA+, TTF-1+, calretinin−).

Aetiology: >80% asbestos-related; latency 20–40 years. Amphibole fibres (crocidolite — blue asbestos) are more carcinogenic than serpentine (chrysotile).

Three-panel medical illustration of pleural mesothelioma showing a thick white pleural rind encasing and compressing the lung with lobulated tumour deposits lining the pleural cavity. — **Panel A:** Gross specimen view showing thick white pleural rind, compressed lung parenchyma, lobulated tumour deposits, and pleural cavity.. **Panel B:** Thoracic cross-section showing pleural cavity, circumferential pleural rind, chest wall, and compressed lung.. **Panel C:** Magnified pleural surface detail showing lobulated pleural tumour deposits and thickened parietal pleura..

H5P Hotspot Activity — Four-Panel Specimen Grid

A 2x2 labelled H&E-style histology grid comparing lobar pneumonia, caseating tuberculosis granuloma, small cell lung carcinoma, and squamous cell carcinoma of the lung. — **Panel A:** Lobar pneumonia showing alveolar neutrophil exudate, fibrin, and intact alveolar walls.. **Panel B:** Caseating tuberculosis granuloma showing central acellular caseation, epithelioid macrophages, and a Langhans giant cell with horseshoe nuclei.. **Panel C:** Small cell lung carcinoma showing small hyperchromatic cells, scant cytoplasm, nuclear moulding, and crush artefact.. **Panel D:** Squamous cell carcinoma showing malignant squamous nests, keratin pearl formation, and intercellular bridges..

Study the four lung specimens in the composite image below. For each panel, identify the diagnosis using the gross and microscopic features described above. Use the hotspot markers to reveal labelled annotations.

A 2x2 labeled histopathology grid compares lobar pneumonia, caseating tuberculosis granuloma, small cell lung carcinoma, and squamous cell carcinoma with key microscopic features annotated. — **Panel A:** Lobar pneumonia with alveolar neutrophil exudate, fibrin, and intact alveolar wall. **Panel B:** Caseating tuberculosis granuloma with central acellular caseation, epithelioid macrophages, and Langhans giant cell. **Panel C:** Small cell lung carcinoma with nuclear moulding, scant cytoplasm, hyperchromatic nuclei, and crush artefact. **Panel D:** Squamous cell carcinoma with keratin pearl and intercellular bridges.

After reviewing each panel:
• Panel A — What exudate type fills the alveoli? (neutrophilic = bacterial)
• Panel B — What do the peripheral nuclei in the giant cell tell you? (Langhans type = TB)
• Panel C — Why does SCLC show crush artefact? (fragile neuroendocrine cells)
• Panel D — What is the significance of keratin pearls? (squamous differentiation = SCC)

SELF-CHECK

In the 2x2 panel grid, Panel B shows a granuloma with central acellular eosinophilic material and a multinucleated giant cell whose nuclei are arranged in a horseshoe pattern at the periphery. This giant cell morphology is:

A. Touton giant cell — characteristic of xanthogranuloma

B. Langhans giant cell — characteristic of TB and sarcoidosis

C. Foreign body giant cell — nuclei randomly scattered

D. Reed-Sternberg cell — characteristic of Hodgkin lymphoma

Reveal Answer

Answer: B. Langhans giant cell — characteristic of TB and sarcoidosis

Langhans giant cells have nuclei arranged in a horseshoe or peripheral wreath pattern — a hallmark of TB and sarcoidosis granulomas. Touton giant cells (lipid vacuoles centrally, peripheral nuclei wreath) are found in xanthogranulomas. Foreign body giant cells have haphazardly distributed nuclei. Reed-Sternberg cells are binucleated owl-eye cells of Hodgkin lymphoma, not giant cells of granulomas.

Putting It Together — Differential Pattern Grid

A diagnostic grid links gross lung specimen patterns to likely respiratory diseases and confirmatory microscopic findings. — **Header:** Gross pattern -> First diagnosis -> Microscopy to confirm. **Row 1:** Lobe-sized consolidation; Lobar pneumonia; alveolar neutrophil exudate with intact alveolar walls. **Row 2:** Patchy grey-yellow foci; Bronchopneumonia; focal purulent bronchiolitis and alveolar exudate. **Row 3:** Upper-lobe cavitated nodule; Tuberculosis; caseating granuloma, Langhans giant cells, optional AFB. **Row 4:** Hyperinflated lung with bullae; Emphysema; alveolar septal destruction without exudate. **Row 5:** Black macules or nodules; CWP / anthracosis; carbon-laden macrophages. **Row 6:** Hard upper-lobe nodules; Silicosis; collagen whorls with birefringent particles. **Row 7:** Pleural plaques with lower-lobe fibrosis; Asbestosis; ferruginous asbestos bodies and interstitial fibrosis.

Use this rapid-read grid when approaching an unknown lung specimen:

Gross finding	First thought	Micro to confirm
Lobe-sized consolidation	Lobar pneumonia	Alveolar neutrophil exudate + intact walls
Patchy grey-yellow foci	Bronchopneumonia	Focal purulent exudate, bronchiolitis
Upper lobe cavitated nodule	TB	Caseating granuloma, Langhans cells, ±AFB
Hyperinflated + bullae	Emphysema	Septal destruction, no exudate
Black macules or nodules	CWP/anthracosis	Carbon-laden macrophages
Hard upper-lobe nodules	Silicosis	Collagen whorls, birefringent particles
Pleural plaques + lower fibrosis	Asbestosis	Asbestos bodies (ferruginous)
Central hilar mass	SCLC or SCC	SCLC: small cells, moulding; SCC: keratin pearls
Peripheral subpleural mass	Adenocarcinoma	Glands, mucin, TTF-1+
Pleural rind	Mesothelioma	Epithelioid/biphasic; calretinin+

Whenever a diagnosis seems ambiguous, ask: Is there exudate (infection), destruction (emphysema/fibrosis), granuloma (TB/sarcoidosis), or abnormal architecture (neoplasm)? These four questions exclude 90% of conditions by pattern.