Page 21 of 32

PA25.6 | Tumours of the Lung & Pleura — SDL Guide (Part 4)

Mesothelioma vs Metastatic Adenocarcinoma — IHC Distinction

Three-panel diagram comparing pleural mesothelioma and metastatic adenocarcinoma using IHC markers, with mesothelioma positive for Calretinin, WT-1, D2-40 and CK5/6, and lung adenocarcinoma positive for TTF-1. — **Panel A:** Pleural space, lung, chest wall, parietal pleura, visceral pleura, pleural tumor deposits, asbestos exposure relevance, diagnostic mimicry. **Panel B:** Malignant mesothelioma, epithelioid mesothelial tumor cells, Calretinin positive, WT-1 positive, D2-40 positive, CK5/6 positive, TTF-1 negative. **Panel C:** Metastatic adenocarcinoma in pleura, gland-forming tumor cells, TTF-1 positive, Calretinin negative, WT-1 negative, D2-40 negative, CK5/6 negative or focal.

A critical diagnostic challenge: malignant mesothelioma (especially epithelioid type) mimics metastatic adenocarcinoma in the pleural space. The distinction is clinically vital because management and legal implications (asbestos compensation) differ entirely.

The IHC panel:

Marker	Mesothelioma	Metastatic Adenocarcinoma
Calretinin	✓ Positive	Negative
WT-1	✓ Positive	Negative
D2-40 (podoplanin)	✓ Positive	Negative
CK5/6	✓ Positive	Negative (or focal)
TTF-1	Negative	✓ Positive (lung adeno)
CEA	Negative	✓ Positive
MOC-31	Negative	✓ Positive

Memory aid: "Calretinin, WT-1, D2-40 = MESothelioma"; TTF-1/CEA/MOC-31 = adenoCarcinoma.

Note: PAS-positive mucin vacuoles → adenocarcinoma. Long microvilli (EM) → mesothelioma.

Pleural effusion cytology alone is often insufficient; pleural biopsy with IHC panel is usually required for definitive diagnosis.

Other Pleural Tumours and Pleural Metastases

A four-panel medical diagram compares pleural metastases, solitary fibrous tumour, pleural plaques, and an asbestos-related mesothelioma self-check using thoracic anatomy, tumour routes, plaques, and IHC labels. — **Panel A:** Thoracic cutaway showing visceral pleura, parietal pleura, pleural cavity, malignant pleural effusion, metastatic tumour deposits, haematogenous route, lymphatic/direct extension, and common primary sources: lung, breast, lymphoma/leukaemia, gastrointestinal cancers.. **Panel B:** Pedunculated solitary fibrous tumour of pleura with submesothelial fibroblast origin, spindle-cell inset, CD34+, STAT6+, IGF-2 secretion, Doege-Potter hypoglycaemia, HPOA, and NOT mesothelioma label.. **Panel C:** Parietal pleural plaques shown as hyalinised collagenous thickenings with asbestos exposure marker, no malignant transformation, and medicolegal evidence labels.. **Panel D:** Self-check diagnostic strip showing shipyard asbestos exposure, pleural tumour biopsy, calretinin-positive, TTF-1 negative, CEA negative, malignant mesothelioma, and 25-45 year latency..

Pleural metastases — the commonest pleural malignancy:
• Secondary involvement of the pleura is far more common than primary mesothelioma.
• Commonest primary sources: lung carcinoma (any subtype), breast carcinoma, lymphoma/leukaemia, gastrointestinal cancers.
• Mechanism: haematogenous seeding of visceral pleura or direct lymphatic extension to parietal pleura.
• Results in malignant pleural effusion — exudate (Light's criteria), often haemorrhagic; cytology positive in ~60%.

Solitary fibrous tumour of the pleura (SFTP):
• Rare; arises from submesothelial fibroblasts (NOT mesothelial cells — hence NOT a mesothelioma).
• Usually benign; pedunculated; CD34-positive, STAT6-positive on IHC.
• Associated with hypoglycaemia (Doege-Potter syndrome — IGF-2 secretion) and HPOA.

Pleural plaques:
• Hyalinised collagenous thickenings on parietal pleura; asbestos exposure marker.
• Do NOT undergo malignant transformation; do NOT cause mesothelioma directly.
• Important as medicolegal evidence of exposure in compensation claims.

SELF-CHECK

Pleural biopsy from a 65-year-old shipyard worker (30 years' asbestos exposure; no smoking) shows a tumour. IHC: calretinin-positive, TTF-1 negative, CEA negative. What is the MOST LIKELY diagnosis and its typical latency from exposure?

A. Metastatic lung adenocarcinoma; 5–10 year latency

B. Malignant mesothelioma; 25–45 year latency

C. Squamous cell carcinoma; 20–25 year latency

D. Solitary fibrous tumour; no asbestos association

Reveal Answer

Answer: B. Malignant mesothelioma; 25–45 year latency

Calretinin-positive, TTF-1-negative, CEA-negative IHC profile is characteristic of malignant mesothelioma. Asbestos (especially amphibole fibres) is the dominant aetiological factor, and the hallmark of mesothelioma is its long latency of 25–45 years from first exposure. Metastatic adenocarcinoma would be TTF-1/CEA-positive. Squamous cell carcinoma typically arises centrally in the bronchus, not the pleura. SFTP has no asbestos association and is usually benign.