Malignant pleural mesothelioma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Malignant pleural mesothelioma arises from pleural mesothelial cells after durable mineral-fibre exposure, most commonly asbestos. Occupational exposure may have occurred during cutting, lagging, drilling, demolition, ship repair or maintenance rather than through a job title labelled asbestos worker. Family exposure from contaminated clothing and environmental exposure also occur. Latency is commonly 30 to 50 years, so a retired person may not connect present symptoms with work early in adult life. Smoking does not cause mesothelioma, although it adds separate lung-cancer risk.

Tumour grows along the pleural surface rather than as one rounded pulmonary mass. Effusion, nodular thickening and a rind encase the lung, restrict expansion and invade intercostal nerves, chest wall, diaphragm and mediastinum. Persistent unilateral pain can be more prominent than breathlessness. Pleural plaques demonstrate prior asbestos exposure but are benign and do not prove that a new effusion is mesothelioma. Conversely, absence of plaques cannot exclude exposure or cancer.

Contrast-enhanced CT with pleural-phase technique defines thickening, nodularity, fissural involvement, chest-wall or diaphragm invasion and a biopsy target. Cytology can diagnose some epithelioid tumours but has insufficient sensitivity for exclusion and may not provide invasion or molecular classification. Image-guided cutting-needle biopsy or thoracoscopy provides deeper tissue, distinguishes epithelioid, sarcomatoid and biphasic histology and supports immunohistochemistry and molecular adjuncts. PET-CT and MRI are selected when staging will alter treatment or clarify invasion, mindful that recent pleurodesis causes inflammatory uptake.

Care integrates fluid control, systemic treatment and symptom support. Talc pleurodesis needs pleural apposition and therefore works poorly in trapped lung; an indwelling pleural catheter allows ambulatory intermittent drainage and may produce spontaneous pleurodesis. Systemic therapy may use platinum-pemetrexed or immunotherapy under current NICE guidance. Extensive radical surgery carries high morbidity and is not routine outside tightly selected specialist or research settings. Pain often needs opioid, neuropathic treatment, radiotherapy and specialist procedures, while compensation and industrial-disease support should be offered sensitively.

Key points

Malignant pleural mesothelioma is a diffuse pleural cancer strongly linked to asbestos exposure after a latency often exceeding several decades.
Key features are progressive unilateral chest pain, breathlessness, recurrent unilateral exudative effusion, pleural nodularity or rind and loss of hemithoracic volume.
Take a detailed lifetime exposure history including job tasks, employers, dates, work clothing, home renovation and para-occupational contact; smoking does not cause mesothelioma.
First-line imaging is contrast-enhanced CT thorax with pleural protocol and upper-abdominal coverage; ultrasound guides fluid and pleural sampling.
Histological core or thoracoscopic pleural biopsy is the diagnostic reference when the patient can tolerate it; do not rely on negative or equivocal cytology alone.
For recurrent symptomatic effusion, choose talc pleurodesis when lung expands or an indwelling pleural catheter when trapped lung, preference or outpatient control favours it.
Systemic treatment is selected from platinum-pemetrexed and current immunotherapy options by histology, performance, comorbidity and NICE eligibility; radical surgery is not routine.
Offer early specialist pain and palliative care and discuss occupational documentation, compensation and benefit routes without making legal support a substitute for clinical treatment.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Occupational asbestos exposure

Inhaled amphibole and chrysotile fibres from construction, shipbuilding, insulation and industrial work create risk after a latency commonly measured in decades.

Para-occupational exposure

Family members exposed to contaminated work clothing and communities near asbestos industry may develop mesothelioma without direct employment in a high-risk trade.

Environmental mineral fibres

Naturally occurring erionite and other durable fibres cause mesothelial carcinogenesis in specific geographical and exposure settings.

Inherited susceptibility

Germline BAP1 tumour-predisposition syndrome is rare but increases mesothelioma and other cancer risk and may justify genetics assessment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Fibres persist in pleura
Long biopersistent fibres migrate to pleural surfaces, resist clearance and repeatedly injure mesothelial cells and resident macrophages.
2
Chronic inflammation damages DNA
Reactive oxygen species, cytokines and repeated repair promote genomic instability over decades after exposure has ceased.
3
Tumour-suppressor pathways fail
Loss involving BAP1, CDKN2A and NF2 permits mesothelial survival, proliferation and altered chromatin and contact-inhibition signalling.
4
Pleural rind restricts lung
Diffuse tumour spreads along pleura, encases lung, invades chest wall and diaphragm and produces fluid, pain, trapped lung and restrictive ventilatory failure.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Unilateral pleural syndrome

Progressive breathlessness, reduced expansion and breath sounds, dull percussion and recurrent fluid suggests a unilateral pleural process requiring imaging.

Invasive chest pain

Persistent local or circumferential pain, night pain and neuropathic intercostal radiation reflects parietal pleural and chest-wall invasion.

Pleural rind imaging

Nodular circumferential pleural thickening, fissural involvement and contraction of the hemithorax is strongly suspicious but still needs tissue.

Trapped lung

Failure of lung re-expansion after drainage, persistent pneumothorax space or pain with fluid removal indicates visceral pleural restriction.

Procedure complicationRed flag

Acute hypoxaemia, severe pain, bleeding or sepsis after biopsy, drain or catheter requires urgent pleural and surgical assessment.

Late systemic disease

Weight loss, cachexia, thrombosis, abdominal involvement or distant metastasis indicates advanced burden and narrows local treatment benefit.

Red flags requiring action

Progressive unilateral chest pain and breathlessness with a recurrent unilateral pleural effusion or diffuse pleural thickening requires urgent pleural investigation.
A history of construction, shipyard, insulation, boiler, railway, military, factory or secondary household asbestos exposure matters even decades later.
Severe breathlessness or mediastinal shift after a pleural procedure raises pneumothorax, haemothorax or re-expansion complication.
Fever, purulent drainage, pleuritic pain or sepsis with an indwelling pleural catheter suggests pleural infection.
New leg swelling, pleuritic pain, syncope or unexplained oxygen requirement raises cancer-associated venous thromboembolism.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line contrast CT thorax and upper abdomenFirst stepFirst line
Why
Characterise pleural tumour, fluid, lung, nodes and invasion and identify a safe biopsy site.
Interpretation and limitations
Use pleural-phase contrast when possible and report fissures, diaphragm, chest wall and mediastinum; CT suspicion does not replace histology.
02
Thoracic ultrasound
Why
Confirm fluid, septation, pleural nodularity and a safe drainage or biopsy path.
Interpretation and limitations
Ultrasound guides procedures and can identify non-expandable lung clues, but it cannot complete cancer stage.
03
Pleural fluid analysis and cytology
Why
Evaluate malignant, infective and alternative exudative causes and sometimes establish epithelioid malignancy.
Interpretation and limitations
Send adequate volume with cell block, but do not use negative cytology to exclude mesothelioma or avoid tissue when the patient is fit for biopsy.
04
Reference tissue biopsy
Why
Confirm invasion and histological subtype and distinguish metastatic carcinoma and reactive mesothelium.
Interpretation and limitations
Use image-guided core or thoracoscopy from viable thickened pleura; obtain enough tissue for mesothelial and carcinoma panels and relevant molecular adjuncts.
05
PET-CT or MRI for selected staging
Why
Define nodal or distant disease and chest-wall or diaphragm invasion when this changes a treatment decision.
Interpretation and limitations
Recent talc pleurodesis causes prolonged FDG uptake, so sequence staging before pleurodesis when PET will be decision-changing and feasible.
06
Pulmonary function and performance assessment
Why
Estimate tolerance and likely benefit from systemic, surgical or radiotherapy options.
Interpretation and limitations
Interpret restriction with fluid and trapped lung and reassess after therapeutic drainage when safe; function and goals matter more than age alone.
07
Occupational exposure record
Why
Support diagnosis, prevention reporting and access to statutory or legal advice.
Interpretation and limitations
Record actual tasks, materials, dates, employers and secondary exposure; absence of remembered asbestos branding does not exclude relevant fibre contact.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Metastatic pleural carcinoma

Lung, breast and other adenocarcinomas commonly involve pleura; immunohistochemical panels distinguish epithelial lineage from mesothelial differentiation.

Benign asbestos pleural disease

Pleural plaques, diffuse benign thickening and rounded atelectasis indicate exposure but do not themselves establish mesothelioma.

Pleural infection or tuberculosis

Fever, inflammatory fluid and pleural thickening can mimic malignancy; microbiology and histology are important when epidemiology or immune status supports infection.

Reactive mesothelial proliferation

Inflamed pleura can show atypical mesothelial cells in fluid or small biopsy; invasion and molecular adjuncts may be needed for confident malignancy.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnoseObtain pleural tissue safelyFirst stepCT and clinical features suggest mesothelioma.

1Take a lifetime task-based asbestos history, assess performance and goals and review contrast CT with the pleural MDT.
2Drain only the amount needed for symptoms and diagnosis while planning image-guided core or thoracoscopy that will provide adequate tissue and stage information.
3Classify epithelioid, sarcomatoid or biphasic disease with specialist pathology and complete only the staging tests capable of changing treatment.

02EffusionMatch fluid control to lung expansionRecurrent pleural fluid causes clinically important breathlessness.

1Perform symptom-guided drainage with manometry or clinical caution when non-expandable lung is suspected and document radiological and symptomatic response.
2DefinitiveOffer talc pleurodesis when lung re-expands and a definitive inpatient or thoracoscopic procedure suits the patient.
3Offer an indwelling pleural catheter for trapped lung, outpatient preference or recurrent disease, teaching drainage, infection and blockage care.

03SystemicChoose treatment from histology and fitnessUnresectable or advanced mesothelioma is confirmed and anticancer treatment is desired.

1Review histology, performance, organ function, autoimmune and transplant context and current NICE eligibility at the mesothelioma MDT.
2Offer platinum-pemetrexed or a funded immunotherapy regimen according to the current indication, explaining response probability and organ-specific toxicity.
3Assess response and clinical benefit early and stop ineffective treatment while maintaining pleural, pain, nutritional and psychosocial care.

04Pain and supportTreat invasive chest-wall morbidityPain, breathlessness or functional and occupational consequences persist alongside tumour treatment.

1Combine regular analgesia, neuropathic adjuvant, radiotherapy or interventional pain options according to the somatic and nerve-invasion pattern.
2Provide pulmonary rehabilitation, fan and breathing support, nutrition, sleep and psychological care and integrate specialist palliative care early.
3Offer benefits, industrial-injury and legal-information routes with consent and accurate exposure records, while protecting clinical time for symptom and cancer decisions.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides cytotoxic first-line disease control for suitable unresectable malignant pleural mesothelioma.

Pemetrexed with platinum

Give pemetrexed 500 mg/m² intravenously on day 1 of each 21-day cycle with cisplatin 75 mg/m² or protocol-selected carboplatin, using the current mesothelioma regimen and organ-function criteria.

Give folic acid and vitamin B12 supplementation and dexamethasone skin prophylaxis exactly as the product protocol; monitor marrow, renal function, infection, mucositis, rash, fatigue and emesis.

Combines PD-1 and CTLA-4 blockade as a first-line option for eligible unresectable disease.

Nivolumab with ipilimumab

Use the licensed weight-based or fixed-dose intravenous combination schedule for unresectable mesothelioma under current NICE TA818 criteria, followed to the protocol duration or stop point.

Dual checkpoint blockade increases immune lung, bowel, liver, endocrine, skin, cardiac, renal and neurological toxicity; review autoimmunity, transplant, infection and steroid requirements and provide urgent contact education.

Treats constant pleural and chest-wall pain while radiotherapy and neuropathic or interventional options are assessed.

Morphine for invasive pleural pain

For an opioid-naive adult with severe persistent pain, start immediate-release oral morphine 2.5 to 5 mg every 4 hours with the same dose for breakthrough, titrating and converting to modified release after stable need is known.

Prescribe laxative and antiemetic when indicated, review sedation, respiration and driving and reduce or select another opioid in renal impairment; pain progression still requires structural reassessment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Recurrent effusion and trapped lung

Fluid reaccumulates while visceral pleural tumour prevents expansion, limiting pleurodesis and causing repeated breathlessness and procedure burden.

Chest-wall and nerve pain

Tumour invades intercostal nerves, ribs and procedure tracts, producing mixed nociceptive and neuropathic pain with sleep and movement impairment.

Restrictive respiratory failure

A thick pleural rind, effusion, atelectasis and diaphragm invasion reduce ventilation and exercise capacity and can lead to oxygen dependence.

Thrombosis and systemic decline

Inflammation, immobility and advanced cancer increase VTE, cachexia, fatigue and loss of independence during progressive pleural disease.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track breathlessness, pain, weight, performance, oxygenation and pleural fluid recurrence rather than relying on tumour dimensions alone.
After an indwelling catheter, monitor drainage trend, pain, skin, cellulitis, pleural infection, blockage and spontaneous pleurodesis with community ownership.
During platinum-pemetrexed, check FBC, renal and liver function, supplementation adherence, infection, neuropathy, hearing and emesis before each cycle.
During immunotherapy, screen every organ system at each contact and after treatment, withholding and treating significant suspected immune toxicity promptly.
Review response at protocol intervals and reassess whether treatment is improving symptoms and function enough to justify continuing burden.
Maintain occupational documentation and confirm referral to benefits or compensation support where the patient wishes.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Plaques are exposure markers

Calcified pleural plaques support past asbestos contact but are benign and neither prove nor exclude a separate malignant pleural process.

Cytology cannot safely exclude

Mesothelioma may shed few diagnostic cells and invasion cannot be assessed reliably in fluid, so adequate pleural tissue is often necessary.

Pleurodesis needs pleural contact

Talc cannot fuse surfaces when tumour prevents the lung reaching the chest wall, making an indwelling catheter more effective in trapped lung.

PET timing matters

Talc produces long-lasting inflammatory avidity that can confuse later staging, so obtain decision-changing PET beforehand when feasible.

Exposure history uses tasks

People may not recognise asbestos by name, but drilling board, removing lagging or washing dusty clothes can reveal meaningful exposure.

11Common pitfallsFrequent interpretation and management errors.

01
Treating pleural plaques as proof that a new effusion is mesothelioma.
02
Excluding mesothelioma from one negative cytology result.
03
Obtaining a superficial or necrotic biopsy that cannot show invasion or subtype.
04
Performing pleurodesis without checking that the lung re-expands.
05
Requesting PET immediately after talc and interpreting inflammatory uptake as tumour stage.
06
Offering radical surgery as routine without specialist selection and evidence discussion.
07
Waiting until anticancer treatment ends before addressing chest-wall pain, breathlessness and occupational support.