Peritoneal mesothelioma
Peritoneal mesothelioma is a rare cancer arising from the mesothelial cells that line the abdominal cavity. It accounts for a minority of all mesotheliomas, the majority of which occur in the chest. For decades it was regarded as uniformly fatal within months. That is no longer accurate: with cytoreductive surgery and heated intraperitoneal chemotherapy in specialist centres, median survival has improved several-fold and long-term survival is achievable in selected patients. This is one of the conditions where being assessed in the right place changes the answer entirely.
How it develops
The peritoneum is lined by a single layer of mesothelial cells, which produce the lubricating fluid allowing the abdominal organs to slide over one another. Mesothelioma arises when these cells become malignant.
Asbestos is the principal recognised cause, though the association is less consistent than for pleural mesothelioma — a definite exposure history is found in only around half of peritoneal cases, and in women it is often absent altogether. The mechanism is thought to involve asbestos fibres reaching the peritoneum either by ingestion of fibres cleared from the lungs and swallowed, or by lymphatic transport from the pleura.
Once in the tissue, the fibres cause harm through several routes:
- Frustrated phagocytosis — macrophages attempt to engulf long, thin fibres they cannot digest, and in the process release reactive oxygen species and inflammatory mediators continuously
- Chronic inflammation — with HMGB1 release and sustained cytokine signalling driving proliferation and resisting cell death
- Direct genetic damage — fibres interfere physically with the mitotic spindle, producing chromosomal abnormalities
The characteristic molecular events are loss of BAP1, loss of CDKN2A, and loss of NF2 — all tumour suppressors. Loss of BAP1 is diagnostically useful, and germline BAP1 mutation defines an inherited tumour predisposition syndrome associated with mesothelioma, uveal and cutaneous melanoma and renal cancer, which is worth considering in younger patients or where there is a suggestive family history.
Other associations include therapeutic radiation, and chronic peritoneal inflammation. Latency is long — typically twenty to forty years after exposure — so the exposure may be remote and easily forgotten; specific questioning about construction, shipbuilding, insulation, plumbing, boilerwork and dockyard employment, and about a partner's or parent's work clothing, is often needed.
Types
- Epithelioid — the commonest and the type with the best outlook; the type most amenable to cytoreductive surgery.
- Sarcomatoid — aggressive, with a poor prognosis and generally not suitable for cytoreductive surgery.
- Biphasic — a mixture, with an intermediate outlook.
- Well-differentiated papillary mesothelioma and multicystic (benign cystic) mesothelioma — borderline tumours, occurring predominantly in younger women, with no asbestos association, an indolent course and a good outlook, though multicystic disease recurs locally. Distinguishing these from malignant mesothelioma is important and changes the treatment completely.
Symptoms
Non-specific and insidious, which is why diagnosis is commonly delayed by six months or more.
- Abdominal distension from ascites — the commonest presentation
- abdominal pain, often vague and diffuse
- a palpable mass
- weight loss, night sweats, fever
- early satiety, nausea, altered bowel habit
- new hernia, with the diagnosis sometimes made from tissue in the sac
- bowel obstruction in advanced disease
- thrombocytosis and venous thrombosis
The combination of ascites and abdominal pain without an identifiable primary tumour elsewhere should raise the possibility.
How the diagnosis is made
- CT of chest, abdomen and pelvis — showing ascites, peritoneal thickening and nodularity, omental caking and mesenteric infiltration. The chest is imaged to look for pleural plaques, which support asbestos exposure, and pleural disease.
- MRI with diffusion-weighted imaging — more sensitive for peritoneal disease extent.
- PET-CT — useful for assessing extent and excluding disease elsewhere.
- Laparoscopy with biopsy — the definitive diagnostic step, giving adequate tissue and allowing assessment of resectability and calculation of the Peritoneal Cancer Index. Ascitic fluid cytology is frequently non-diagnostic, and a negative cytology should not be taken as excluding the diagnosis.
- Immunohistochemistry — essential, and the diagnosis should not be made without it. Mesothelioma is typically positive for calretinin, WT1, CK5/6 and D2-40, and negative for the markers of adenocarcinoma (CEA, MOC-31, Ber-EP4, claudin-4). Loss of BAP1 expression and deletion of CDKN2A by FISH distinguish malignant mesothelioma from reactive mesothelial proliferation, which can look deceptively similar — a genuinely difficult distinction that has led to both over- and under-diagnosis.
Because the histological diagnosis is difficult, review by a pathologist experienced in mesothelioma is advisable.
Treatment
Cytoreductive surgery with HIPEC
This is the treatment of choice for selected patients and has transformed the outlook. It involves removal of all visible disease by peritonectomy and organ resection, followed by heated intraperitoneal chemotherapy — commonly cisplatin with doxorubicin, or mitomycin C.
Unlike in colorectal peritoneal metastases, where the role of HIPEC has been questioned, the evidence supporting it in peritoneal mesothelioma is consistent, and this combination is accepted as standard of care in specialist centres.
Favourable factors for surgery are epithelioid histology, disease that can be completely removed, absence of extensive small bowel and mesenteric involvement, no disease outside the abdomen, no lymph node involvement, and adequate fitness. Sarcomatoid histology is generally a contraindication.
Systemic treatment
- Chemotherapy — platinum with pemetrexed is the standard regimen, used for unresectable disease and sometimes before or after surgery.
- Immunotherapy — combination checkpoint inhibition (nivolumab with ipilimumab) has become an established first-line option, with particular benefit in non-epithelioid disease where chemotherapy performs poorly.
- Antiangiogenic agents added to chemotherapy in some settings.
- Clinical trials are especially relevant in this disease and are worth asking about.
Palliative measures
Management of ascites by paracentesis or indwelling drain; treatment of obstruction; nutritional support; pain management; and early specialist palliative care.
Medico-legal and benefits
Where asbestos exposure is identified, patients may be entitled to state compensation or to pursue a civil claim, and in many jurisdictions the diagnosis is reportable. This is a practical matter that makes a real difference to families and is easily overlooked in the clinical discussion. Taking a careful occupational history early, while the patient is able to give it, is important for this reason as well as the diagnostic one.
Recovery
Cytoreductive surgery with HIPEC involves a hospital stay of two to three weeks, usually including critical care, with a significant complication rate and a recovery of three to six months. Chemotherapy and immunotherapy have their own well-described side-effect profiles.
Follow-up
Regular clinical review and CT surveillance. Recurrence is common and may be amenable to repeat cytoreduction in selected patients with good initial control.
When to seek an opinion
Unexplained ascites, particularly with abdominal pain and no identifiable primary tumour, warrants laparoscopy rather than repeated drainage. Any diagnosis of peritoneal mesothelioma should be discussed with a specialist peritoneal malignancy centre before treatment is decided, because the surgical option is not available everywhere and the difference in outcome is substantial.
Common questions
Is this the same as the lung mesothelioma caused by asbestos?
It is the same type of cancer, arising from the same lining cells, but in the abdomen rather than around the lungs. It is much less common, and the link with asbestos, while real, is found in only around half of cases — particularly in women, where an exposure history is often absent.
I do not remember any asbestos exposure. How can I have this?
Exposure is often decades in the past — typically twenty to forty years — and may have been brief or indirect, such as washing work clothes belonging to a family member, or living near a workplace. In a proportion of cases no exposure is ever identified, and the cause is unknown. Either way, this is worth discussing carefully, because it can matter for compensation.
How long do I have?
This depends heavily on the type of cells and whether surgery is possible, and the figures you may have read are often out of date. Untreated, the outlook is poor. With complete surgery and heated chemotherapy in a specialist centre, patients with the commonest (epithelioid) type frequently live for years, and long-term survival occurs. The more aggressive types have a worse outlook, and that should be said plainly too.
Is surgery an option for me?
It depends on the type of cells under the microscope, how extensive the disease is — particularly whether the small bowel and its supporting tissue are heavily involved — whether there is disease outside the abdomen, and your fitness for a long operation. A laparoscopy is usually needed to answer this properly, because scans underestimate the extent.
Why was the fluid drained from my abdomen not diagnostic?
Because the cells in the fluid are frequently insufficient or ambiguous, and mesothelioma cells can look very similar to normal reactive lining cells. A tissue sample taken at laparoscopy, with specialised staining, is usually needed. A negative fluid test does not exclude the diagnosis.
Does immunotherapy work for this?
Yes, and it has become an established treatment option, given as a combination of two drugs. It appears particularly useful for the more aggressive cell types, which respond poorly to conventional chemotherapy. Whether it is the right first treatment for you depends on the cell type and on whether surgery is being considered.
Can I claim compensation?
In many countries yes, where asbestos exposure is established, through state industrial injury schemes or a civil claim. It is worth raising early, and a careful record of where and when you may have been exposed, taken while you are well, is valuable. Your clinical team can usually point you to the right advice.
Should I get a second opinion on the pathology?
It is reasonable. Distinguishing mesothelioma from a reactive, non-cancerous proliferation of the same cells is genuinely difficult, and specific tests — such as loss of the BAP1 protein — are used to make the distinction. Review by a pathologist who sees this condition regularly is worthwhile, particularly as the diagnosis carries such significant consequences.
Related conditions
Other conditions of the peritoneal disease covered on this site:
- Peritoneal metastases
- Pseudomyxoma peritonei
- Primary peritoneal cancer
- Peritonitis
- Intra-abdominal abscess
- Adhesions and adhesive bowel obstruction
This page provides general information and does not replace an individual medical consultation. Peritoneal mesothelioma should be assessed in a specialist peritoneal malignancy centre.