Malignant Mesothelioma
Summary
Malignant Mesothelioma (MM) is an aggressive, incurable neoplasm arising from the mesothelial cells of the pleura (or rarely peritoneum/pericardium). It is intrinsically linked to Asbestos exposure, with a latency period of 20-50 years. Due to peak asbestos use in the 1970s, incidence is currently peaking in the UK/Australia. Immunotherapy (Ipilimumab + Nivolumab) has recently revolutionized treatment, replacing Chemotherapy as the standard of care for many patients. [1,2]
Clinical Pearls
The "Frozen Hemithorax": On examination, a mesothelioma patient often has a chest that simply does not move on one side. The tumour forms a restrictive "rind" that encases the lung, preventing expansion even if the fluid is drained.
Procedural Tract Metastasis: Mesothelioma is uniquely notorious for "seeding" along biopsy tracks or drain sites. Historically, these tracks were irradiated prophylactically. However, the PIT Trial proved this is unnecessary.
The "Boring" Pain: Unlike pleurisy (sharp with breath), invasion of the chest wall causes a deep, gnawing, "toothache-like" pain that is often neuropathic and very difficult to treat (often requiring Methadone).
Demographics
- Incidence: 2,500 deaths/year in UK (highest rate in world). Peaking now.
- Latency: 30-50 years.
- Gender: M >> F (Occupational bias).
Asbestos Types
- Amphiboles: Straight, sharp fibers. Highly carcinogenic because macrophages cannot clear them.
- Blue (Crocidolite): Most dangerous.
- Brown (Amosite): Dangerous.
- Serpentine: Curved fibers.
- White (Chrysotile): Less dangerous (controversial, but used in most braking pads/roofing).
Mechanism of Carcinogenesis
- Inhalation: Fibres are small enough to reach distal alveoli.
- Translocation: Fibres pierce the lung and migrate to the pleural space.
- "Frustrated Phagocytosis": Macrophages try to engulf the long fibers but fail. They release Reactive Oxygen Species (ROS) and Cytokines constantly for decades.
- DNA Damage: Chronic inflammation + direct interference with mitosis -> Loss of tumour suppressors (BAP1, NF2).
Histological Subtypes
- Epithelioid (60%): Best prognosis.
- Sarcomatoid (10-20%): Spindle cells. Poor prognosis. Resistant to chemo.
- Biphasic (20%): Mixed.
Symptoms
- Chest: Stony dullness (Effusion). Reduced expansion.
- Clubbing: Paradoxically RARE in mesothelioma (but common in Asbestosis/Lung Cancer).
- Abdomen: Check for peritoneal mass (dual pathology).
Imaging
- CXR: Unilateral effusion. Lobulated pleural thickening.
- CT with Contrast: "Rind-like" circumferential thickening. Mediastinal pleural involvement. Volume loss on affected side.
Biopsy (Essential)
Fluid cytology is insensitive (sensitivity less than 30%). Tissue is required.
- Thoracoscopy (Medical/VATS): Gold standard. Allows biopsy + talc pleurodesis.
- CT-Guided Core Biopsy: If mass is accessible.
Biomarkers
- Mesothelin: Raised in blood/fluid (limited sensitivity).
- Immunohistochemistry: Calretinin (+), CK5/6 (+), TTF-1 (Negative - excludes adenocarcinoma).
Management Algorithm
CONFIRMED MESOTHELIOMA
↓
STAGING [CT/PET]
(Check for distant metastasis)
↓
ASSESS PERFORMANCE STATUS (PS)
┌─────────┴─────────┐
PS 0-1 (Fit) PS 2+ (Frail)
↓ ↓
SYSTEMIC THERAPY BEST SUPPORTIVE CARE
- **Immunotherapy** - Palliative Care
(Ipi + Nivo) - Opioids
*Preferred* - Palliative RT
- Chemotherapy
(Pemetrexed +
Cisplatin)
↓
PLEURAL FLUID MANAGEMENT
- Indwelling Pleural Catheter (IPC)
(Best for trapped lung)
- Talc Pleurodesis (Video Assisted)
Systemic Therapy
- Immunotherapy: Nivolumab + Ipilimumab (Dual Checkpoint Inhibition).
- CheckMate 743 Trial: Showed superior survival to chemotherapy, especially in sarcomatoid subtypes (median survival 18.1m vs 8.8m in non-epithelioid). Now First Line (NICE 2022).
- Chemotherapy: Pemetrexed + Cisplatin.
- Former gold standard (Vogelzang trial). Still used if immunotherapy contraindicated.
Surgery (MARS 2 Trial)
- Extra-Pleural Pneumonectomy (EPP): Radical removal of lung/pleura/diaphragm.
- Pleurectomy/Decortication (PD): Lung sparing debulking.
- Current Consensus: The MARS 2 Trial (2023) showed that surgery (PD) increased complications/death and did not improve survival compared to chemo alone. Surgery is largely being abandoned outside of trials.
- Trapped Lung: Lung cannot re-expand due to visceral pleural thickening. Fluid drains but air space remains. Best managed with IPC.
- SVC Obstruction.
- Pericardial Tamponade.
- Spinal Cord Compression: Direct invasion.
- Median Survival: 12-18 months (improved from 9 months pre-immunotherapy).
- Poor Prognostic Factors: Sarcomatoid type, High WCC, Low Hb, Poor Performance Status, Male gender (CALGB Score).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Mesothelioma | BTS (2018) | Diagnosis and fluid management. |
| New Therapies | NICE (2022) | Immunotherapy approval. |
Landmark Evidence
1. CheckMate 743 (Lancet 2021)
- The trial that changed the paradigm. Ipilimumab + Nivolumab vs Chemo.
- 4 year survival: 17% (Immuno) vs 11% (Chemo).
- Huge benefit in Sarcomatoid histology (Hazard Ratio 0.46).
2. MARS 2 (WCLC 2023)
- The "nail in the coffin" for radical surgery. Surgery arm had worse survival than Chemo alone.
What is Mesothelioma?
It is a cancer of the lining of the lung (the pleura), caused by exposure to asbestos. It is not lung cancer (which is inside the lung), but a cancer of the "shrink wrap" around the lung.
Why now? I worked with asbestos 40 years ago.
Asbestos fibers are indestructible. Once inhaled, they sit in the lining of the lung for decades, causing slow irritation. It takes 30-50 years for this irritation to turn into cancer. This is why we see so many cases today from the building boom of the 1970s.
Treatment
We cannot usually cut it out because it grows like a sheet rather than a lump. However, we have very effective new treatments (Immunotherapy) that boost your own immune system to fight the cancer, which work much better than old-fashioned chemotherapy.
Compensation
Because this is an industrial disease, you are almost certainly entitled to government compensation. We will help you with the paperwork.
Primary Sources
- Baas P, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021.
- Lim E, et al. Pleurectomy Decortication but not Extrapleural Pneumonectomy for malignant pleural mesothelioma (MARS 2). WCLC Presentation. 2023.
- Woolhouse I, et al. British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. Thorax. 2018.
Common Exam Questions
- Diagnosis: "Bloody effusion + Chest pain + Asbestos?"
- Answer: Mesothelioma.
- Histology: "Calretinin Positive, TTF-1 Negative?"
- Answer: Mesothelioma (TTF-1 positive would be Lung Adenocarcinoma).
- Treatment: "Best systemic therapy for Sarcomatoid type?"
- Answer: Ipilimumab + Nivolumab.
- Surgical: "Role of EPP?"
- Answer: Rarely indicated (high mortality/no benefit vs chemo in MARS 2).
Viva Points
- Why is fluid cytology poor?: Mesothelioma cells look very similar to reactive mesothelial cells (which occur in any inflammation). Only a tissue biopsy showing invasion into fat/muscle proves malignancy definitively.
- Trapped Lung: If CXR shows hydropneumothorax after drainage without a leak, the lung is trapped. Talc won't work (layers can't stick). Use an IPC.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.