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Mesothelioma
Biopsy, Staging, and an Honest Answer About Surgery

Mesothelioma cannot be diagnosed on a scan. It is diagnosed on a specimen, and the subtype found in that specimen decides which treatments are worth giving. The surgeon's work in mesothelioma is to obtain that specimen reliably, to stage the disease properly, and to control the fluid that causes the breathlessness — usually in a single anaesthetic. For most patients an operation to remove the tumour is not the right treatment. For a small minority it remains a real question, and it deserves a proper answer rather than a reflex.

Last reviewed: 14 July 2026 · Mr Lawrence Okiror FRCS(CTh) FRCSEd(CTh) · GMC 6150382

Every other cancer of the chest is now, to some degree, an imaging problem: a nodule is measured, tracked, and modelled, and the picture carries a great deal of the decision. Mesothelioma is not like that. A scan can tell you that something is wrong with the pleura and roughly how much of it there is. It cannot tell you what the disease is, and it cannot tell you what to do about it. The whole of the treatment — whether chemotherapy or immunotherapy is first-line, whether an operation is even a question, what the outlook realistically is — turns on the histological subtype, and the subtype comes from a specimen. That is why the first decision in mesothelioma is not which treatment, but how the tissue is obtained.

Key Takeaways

  • No scan diagnoses mesothelioma. CT, PET-CT and MRI raise the suspicion and measure the disease. Only a specimen names it — and the subtype reported on that specimen is the single strongest determinant of what treatment is worth giving.
  • VATS pleural biopsy is the definitive test. Pleural fluid cytology is positive in only a minority of mesotheliomas. Keyhole biopsy under direct vision gives a large, reliable specimen — adequate for subtyping and for the molecular work that now guides treatment.
  • Whether the lung re-expands decides how the fluid is treated. If it re-expands, talc pleurodesis can seal the space permanently. If the lung is trapped by a rind of tumour, pleurodesis will fail and an indwelling pleural catheter is the better answer. The lung decides, not the surgeon.
  • Radical surgery is not offered for most mesothelioma — and that is the evidence talking. The MARS2 randomised trial found that adding extended pleurectomy/decortication to chemotherapy shortened survival and caused substantially more serious complications.
  • A small minority of patients are a genuine question. Early-stage, node-negative, epithelioid disease in someone fit to complete the whole of their treatment is a different situation, and the international literature no longer treats the two the same way. Telling them apart requires staging, not an opinion.

How is mesothelioma diagnosed, and why does the biopsy decide everything?

Most patients reach a thoracic surgeon after a chest X-ray or CT has shown fluid around the lung, often with thickening of the pleural lining, and often after the fluid has already been drained once. The fluid is sent for cytology, and in mesothelioma it comes back unhelpful more often than not — for a reason worth understanding. Mesothelioma sheds relatively few cells into the fluid, and the cells it does shed are hard to distinguish from the reactive mesothelial cells that any irritated pleura produces. A negative or equivocal cytology therefore does not lower the suspicion of mesothelioma at all; repeating the tap is the commonest cause of delay in this disease.

There is a deeper reason a small or superficial sample fails. The single feature that separates an invasive mesothelioma from a benign, reactive process is invasion itself — malignant cells breaching the surface and infiltrating the underlying fat or muscle. Fluid cytology cannot show that, and neither can a shallow biopsy that never reaches the deep tissue; both are commonly reported as atypical mesothelial proliferation, which sounds like a diagnosis but is not one. It means the pathologist can see abnormal cells but cannot see whether they are invading, and so cannot call the disease malignant. The specimen has to be deep enough, and large enough, to answer that question.

The definitive test is therefore a pleural biopsy. Where a CT-guided needle biopsy of thickened pleura is feasible it is a reasonable route. Where it is not — or where it has already been tried and been non-diagnostic — keyhole (VATS) pleural biopsy under general anaesthetic is the reference standard. The pleural cavity is inspected directly through one or two small incisions, the fluid is fully drained, and biopsies are taken from the abnormal pleura under vision rather than blindly, deep enough to show whether the disease is invading.

Three things follow from doing this properly. The specimen is large enough to subtype the disease confidently — epithelioid, biphasic or sarcomatoid — and that distinction now does real work in treatment, not only prognosis: non-epithelioid mesothelioma derives markedly greater benefit from first-line immunotherapy (nivolumab and ipilimumab) than epithelioid disease, in which chemotherapy and immunotherapy perform more comparably. The subtype genuinely steers which systemic treatment leads, so it has to be established on adequate tissue rather than guessed from a sliver. The specimen is large enough, too, for the immunohistochemistry that confirms the diagnosis and rules out the cancers that imitate it. And the extent of disease inside the chest is seen rather than inferred from a picture, which is the beginning of honest staging.

What the biopsy has to deliver
  • A confident histological subtype — epithelioid, biphasic or sarcomatoid — which now steers systemic treatment, not only prognosis
  • Enough depth to demonstrate invasion — what separates malignant disease from a reactive proliferation — and enough tissue for confirmatory immunohistochemistry
  • Direct visual assessment of how far the disease extends within the chest
  • Treatment of the effusion in the same anaesthetic, where the lung allows it
Staging: what is actually needed
  • PET-CT, to look for disease beyond the hemithorax
  • Histological assessment of the mediastinal nodes where an operation is being contemplated — usually by endobronchial ultrasound (EBUS)
  • Measurement of pleural thickness, which now carries weight in the current staging system
  • Discussion at a specialist mesothelioma multidisciplinary meeting before any treatment begins

What can be done about the fluid and the breathlessness?

The breathlessness of mesothelioma is usually mechanical. Fluid accumulates in the pleural space and compresses the lung, and the patient cannot fill their chest. Draining it brings immediate relief — and then, in most cases, it comes back.

The decision about how to stop it coming back rests on a single observation: does the lung re-expand once the fluid is out? If it does, the two pleural surfaces can be brought into contact and sealed, and talc pleurodesis will usually hold. If the lung is trapped — encased in a rind of tumour that physically prevents it re-expanding — then there is no surface to seal against, pleurodesis will fail, and putting a patient through it is a wasted admission.

For a trapped lung, an indwelling pleural catheter is the better answer: a soft tube tunnelled under the skin, drained at home by the patient or a district nurse, with no repeated hospital visits. It does not treat the cancer. It treats the breathlessness, which is what the patient came in with.

If the lung re-expands

Talc pleurodesis, usually at the same anaesthetic as the biopsy. The pleural space is obliterated and the fluid cannot re-accumulate. One admission, one anaesthetic, diagnosis and treatment together.

If the lung is trapped

An indwelling pleural catheter, drained at home. Pleurodesis in a trapped lung does not work, and offering it anyway costs the patient a hospital stay for nothing.

The general principles of fluid, drainage and pleurodesis are set out on the pleural disease page →

Is surgery to remove the mesothelioma an option?

For most patients, no — and it is worth being direct about why, because this is a question on which a great deal of confusing material exists online.

Two operations have historically been offered. Extrapleural pneumonectomy removed the pleura, the lung, the diaphragm and the pericardium together; it was largely abandoned in the UK after a randomised feasibility study in 2011 reported excess deaths in the surgical arm. Extended pleurectomy/decortication spares the lung but takes the pleura and, in most published series, the diaphragm as well.

In 2024 the MARS2 randomised controlled trial compared chemotherapy alone against chemotherapy plus extended pleurectomy/decortication. Median survival was 24.8 months without surgery and 19.3 months with it, and serious adverse events ran at more than three times the rate in the surgical arm. British practice changed within months, and I stopped offering the operation.

What has happened since is more interesting than the trial itself, and it does not amount to a reversal. The trial's own lead recruiter subsequently restaged half of the surgical arm against the current staging system and found that only one in three of those patients would have been offered an operation under contemporary selection criteria — and that the survival of that one in three was very different from the survival of the two-thirds who should not have been operated on. An international expert consensus published in 2026 places surgery inside a multimodal regimen conditional on selection, multidisciplinary assessment, and the experience of the surgeon and centre.

The honest position, which is the one I hold, is this. For advanced disease, for non-epithelioid subtypes, and for anyone in whom the nodes have not been properly assessed, an operation to remove mesothelioma is not the right treatment, and no amount of surgical enthusiasm changes that. For a small number of patients — early-stage, node-negative, epithelioid disease, in someone well enough to complete the rest of their treatment — the question is genuinely open, is contested internationally, and belongs in a specialist multidisciplinary discussion rather than in a single surgeon's opinion. I have written at greater length about what MARS2 did and did not settle in the Journal.

What this means in practice
  • Everyone gets a proper tissue diagnosis and proper staging first. Nothing is decided before that.
  • The effusion is controlled, because the breathlessness is what most affects how a patient actually lives.
  • Systemic treatment is led by the oncologist, and the subtype is what steers it.
  • Resection is discussed only where the staging supports the question, and always at a specialist mesothelioma multidisciplinary meeting.

When is a second opinion worth having?

Early — while the choices are still open. Mesothelioma is uncommon, the decisions turn on details of subtype and stage that are easy to get wrong, and the single most consequential question in the disease (whether surgery has any part to play at all) is one on which serious people disagree. A second opinion after treatment has started is worth much less than a second opinion before it does.

What is useful to bring: the CT and PET-CT images themselves, not only the reports; the histology report and, where possible, the pathology slides; and a note of what has already been drained, biopsied or attempted. With those in hand a second opinion can be substantive rather than a restatement of what you already know.

Mr Okiror is a Consultant Thoracic and Robotic Surgeon at Guy's and St Thomas' NHS Foundation Trust, which runs a specialist mesothelioma multidisciplinary team, and has published on the staging of pleural mesothelioma, on pleurectomy/decortication within multimodality treatment, on PET-CT surveillance after surgery, and on survival in advanced disease. Private consultations are held at London Bridge Hospital and The Lister Hospital Chelsea.

Practical, emotional and welfare support for patients and families is available from Mesothelioma UK, an independent charity with specialist nurses across the country.

Related

Pleural Disease → Journal: One in three → Pleural Surgery Reference → Breathlessness → Second Opinion →

Questions About
Mesothelioma

Common questions from patients and referrers. If your question is not answered here, please get in touch directly.

Book a Consultation →

Or call Jo Mitchelson:
020 7952 2882

Can a scan tell me whether I have mesothelioma?
No. A CT or PET-CT scan can show pleural thickening, fluid and nodularity that make mesothelioma likely, and can measure how much disease is present, but it cannot make the diagnosis. Mesothelioma is diagnosed on tissue. A pleural biopsy — usually a keyhole (VATS) biopsy under direct vision — is required, and the subtype reported on that specimen is what determines which treatments are worth giving.
Why is my pleural fluid test not enough?
Draining fluid and sending it for cytology is a reasonable first step, but in mesothelioma it is positive in only a minority of cases. Mesothelioma sheds few cells into the fluid, and those it sheds are hard to tell apart from the reactive cells any irritated pleura produces — and cytology can never show whether the disease is invading the deeper tissue, which is what distinguishes cancer from a reactive process. Even a positive sample is often too small to subtype reliably. Where mesothelioma is suspected and the fluid is unhelpful, the next step is a biopsy, not another tap.
What is a VATS pleural biopsy?
Keyhole surgery under general anaesthetic, through one or two small incisions. The pleural cavity is inspected directly, the fluid is fully drained, and biopsies are taken from the abnormal pleura under vision. It gives a large, reliable specimen, allows the extent of disease to be seen rather than inferred, and lets the effusion be treated in the same anaesthetic — usually with talc pleurodesis if the lung re-expands.
How is the breathlessness treated?
Breathlessness in mesothelioma is usually caused by fluid compressing the lung, and the treatment depends on one thing: whether the lung re-expands once the fluid is removed. If it does, talc pleurodesis seals the space and prevents the fluid returning. If the lung is trapped by tumour and will not re-expand, pleurodesis will not work, and an indwelling pleural catheter — drained at home, without repeated hospital visits — is the better option.
Will I be offered an operation to remove the mesothelioma?
For most patients, no. The MARS2 randomised trial, reported in 2024, found that adding extended pleurectomy/decortication to chemotherapy shortened median survival and caused substantially more serious complications, and British practice changed accordingly. A small minority of patients — early-stage, node-negative, epithelioid disease, in someone fit to complete the rest of their treatment — remain a genuine question, and are discussed individually at a specialist mesothelioma multidisciplinary meeting. Read the longer argument →
Is a second opinion worth having?
Yes, and it is worth having early. Mesothelioma is uncommon, the treatment decisions turn on details of subtype and stage that are easy to get wrong, and the question of whether an operation has any part to play is genuinely contested internationally. A second opinion is most useful before treatment starts, while the choices are still open. Second opinion page →
Do I need a GP referral to be seen privately?
Self-referrals are welcome. Appointments are typically available within 2–3 days at London Bridge Hospital or The Lister Hospital Chelsea. If you have recent scans or a biopsy report, bringing them to the first appointment makes the consultation considerably more useful.

Book a Consultation

Appointments within 2–3 days. Self-referrals welcome. London Bridge Hospital and The Lister Hospital Chelsea.

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Jo Mitchelson, PA  · 020 7952 2882 · pa@lungsurgeon.co.uk

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