Peritoneal Mesothelioma: Symptoms, Types, Causes and Treatment

Peritoneal mesothelioma is a rare and aggressive cancer that originates in the lining of the abdominal cavity, known as the peritoneum. Despite its rarity, awareness and knowledge about this disease are crucial for early detection and improved outcomes. In this article, we will explore the symptoms, types, causes, and the latest treatment approaches for peritoneal mesothelioma, drawing on the latest research and clinical experience.

Symptoms of Peritoneal Mesothelioma

Peritoneal mesothelioma often presents insidiously, making early diagnosis challenging. The initial symptoms are typically non-specific and can mimic more common abdominal conditions, which frequently leads to delays in diagnosis. Recognizing these symptoms early is vital for timely intervention.

Symptom	Frequency/Prevalence	Clinical Impact	Source
Abdominal Pain	Most common (33–50%)	Often localized; may relate to tumor mass	1,2,3,4,5
Ascites (Fluid buildup)	Very common (up to 61%)	Causes abdominal distension/girth	1,2,3,4,5
Weight Loss	Frequent, especially advanced	Indicator of disease progression	1,4,2
Anorexia	Reported in many cases	Associated with weight loss and malaise	1,4
Abdominal Mass	Sometimes present	Palpable in advanced cases	1,4
Fever	Less common	Nonspecific; may indicate inflammation	1,4
Vomiting/Diarrhea	Occasionally reported	Related to bowel involvement	1,4
Hernia	New onset in some patients (12%)	May be presenting sign	2
Asthenia (Fatigue)	Not uncommon	Generalized weakness	1,4

Table 1: Key Symptoms

Common Presenting Symptoms

The most frequent presenting symptom is abdominal pain, reported in up to half of patients. This pain may be localized and often relates to the presence of a dominant tumor mass. Closely following is abdominal distension, caused by the accumulation of fluid (ascites) within the abdominal cavity. Ascites may lead to a noticeable increase in abdominal girth, which can be distressing and is sometimes the initial sign prompting further investigation 1,2,3,4,5.

Other common symptoms include:

• Weight Loss and Anorexia: Many patients experience unintentional weight loss and loss of appetite, which can reflect disease progression or systemic involvement 1,4.
• Abdominal Mass: In some cases, a palpable mass may be detected, especially as the disease advances 1,4.
• Fatigue (Asthenia): Generalized weakness or fatigue is reported by many patients and can significantly impact daily life 1,4.
• Gastrointestinal Symptoms: Less commonly, patients may present with vomiting, diarrhea, or even new-onset hernias. These symptoms often occur when the tumor affects the gastrointestinal tract or increases intra-abdominal pressure 1,2,4.

Symptom Variability and Diagnostic Challenges

The variability and non-specific nature of symptoms often lead to misdiagnosis or delayed diagnosis. Some patients may initially undergo evaluation for much more common abdominal conditions such as irritable bowel syndrome, gastrointestinal infections, or ovarian disease before peritoneal mesothelioma is considered 5. In rare cases, fever may be present, reflecting the inflammatory nature of the disease 1,4.

Patients with smaller tumors or lower disease volume may be asymptomatic or present with very subtle symptoms, further complicating early detection. Notably, the prognosis is generally better for women and for patients who have a lower volume of disease at the time of diagnosis 2,3.

Types of Peritoneal Mesothelioma

Peritoneal mesothelioma is not a single, uniform disease. It encompasses several histological and clinical subtypes, each with differing behaviors and prognoses. Understanding these types can guide both diagnosis and management.

Type/Subtype	Key Characteristics	Prognosis/Behavior	Source
Diffuse Malignant	Most common; widespread peritoneal involvement	Aggressive, poor prognosis	1,3,4,6,7
Localized	Rare; solitary mass	Sometimes less aggressive	6,8
Epithelioid	Most prevalent cell type	Better prognosis	3,16
Sarcomatoid	Spindle-shaped cells	Worse prognosis	16
Biphasic	Mixed epithelioid and sarcomatoid cells	Intermediate prognosis	8,16
Multicystic	Benign or indolent, often in women	Good prognosis, non-malignant	6
Well-differentiated Papillary	Rare, low-grade, often in women	Indolent, excellent outcome	6,8

Table 2: Subtypes of Peritoneal Mesothelioma

Histological Subtypes

• Epithelioid: This is the most common histological subtype, characterized by cells resembling normal mesothelial cells. It is associated with a relatively better prognosis and tends to respond more favorably to therapy 3,16.
• Sarcomatoid: Exhibiting spindle-shaped cells, this subtype is rare in the peritoneum and linked with a much poorer prognosis due to its aggressive nature 16.
• Biphasic: Contains both epithelioid and sarcomatoid elements, with an intermediate clinical outcome 8,16.

Clinical Presentation: Diffuse vs. Localized

• Diffuse Malignant Peritoneal Mesothelioma: By far the most common clinical form, this type involves widespread thickening and nodularity of the peritoneal surfaces. It is highly aggressive, with a tendency to remain within the abdomen rather than metastasize to distant organs. This pattern is responsible for most clinical presentations and deaths 1,3,4,7.
• Localized Peritoneal Mesothelioma: Rarely, the disease may present as a solitary mass. These cases may behave less aggressively and can sometimes be resected with curative intent 6,8.

Other Peritoneal Tumors

• Multicystic Mesothelioma: While not truly malignant, this variant is notable for its benign or indolent behavior, often affecting women. It consists of multilocular cystic masses and rarely transforms into a malignant form 6.
• Well-differentiated Papillary Mesothelioma: Another indolent entity, this type is low-grade, slow-growing, and generally has an excellent prognosis, especially in women 6,8.

Molecular Subtypes

Recent research has uncovered molecular subtypes based on genetic alterations, such as BAP1 mutations and ALK rearrangements. These molecular features may eventually guide targeted therapies and personalized treatment approaches 8,11,12,16.

Causes of Peritoneal Mesothelioma

The causes of peritoneal mesothelioma are multifactorial, involving environmental, occupational, and genetic factors. Understanding these can help in prevention and risk reduction.

Cause/Risk Factor	Description/Details	Relative Importance	Source
Asbestos Exposure	Occupational/environmental inhalation or ingestion	Main known cause	4,9,10,13,16
Erionite Exposure	Natural mineral fiber, highly carcinogenic	Rare, geographically limited	9,10
Radiation Exposure	Therapeutic radiation to abdomen	Rare, possible risk factor	9,12
Genetic Predisposition	Germline mutations (e.g., BAP1)	Important in some cases	9,11,12,8
ALK Rearrangements	Unique molecular alteration, esp. in young women	Rare, actionable target	12,8,16
Other Suspected Factors	SV40 virus, Thorotrast, chronic inflammation	Unclear, less established	9,10

Table 3: Causes and Risk Factors

Asbestos: The Primary Culprit

Asbestos exposure remains the single most important risk factor for developing peritoneal mesothelioma. Both direct occupational exposure (e.g., construction, insulation, shipbuilding) and environmental exposure (proximity to asbestos mines or contaminated buildings) have been implicated. Asbestos fibers can be inhaled or ingested, eventually reaching the peritoneum, where they trigger chronic inflammation and DNA damage in mesothelial cells 4,9,10,16.

• In men, about 30% of peritoneal mesothelioma cases are linked to asbestos, whereas the association is weaker in women 9,16.
• The type of asbestos matters: amphibole forms are more potent than chrysotile in causing mesothelioma 10.

Other Environmental and Occupational Risks

• Erionite: This naturally occurring mineral fiber is even more carcinogenic than asbestos but is geographically restricted (notably Turkey and parts of the US) 9,10.
• Radiation: Therapeutic abdominal or pelvic radiation has been implicated in rare cases 9,12.
• Thorotrast: A historical radiographic contrast agent, now obsolete, has been associated with rare cases 10.

Genetic and Molecular Factors

• Genetic Predisposition: Germline mutations, particularly in the BAP1 gene, greatly increase susceptibility to mesothelioma. Families with inherited BAP1 mutations have higher rates of both pleural and peritoneal mesothelioma and other cancers 8,11,12.
• ALK Rearrangements: Recent studies have identified unique ALK gene rearrangements in peritoneal mesothelioma, particularly in young women with no asbestos exposure. These cases lack typical genetic changes seen in other mesotheliomas and may be amenable to targeted therapy 12,8,16.

Other Factors

• Simian Virus 40 (SV40): Some studies suggest an association with SV40 infection, but this remains controversial and unproven 9,10.
• Chronic Inflammation: Prolonged peritoneal inflammation from other causes may play a role, though this is less well established 9.

Treatment of Peritoneal Mesothelioma

Management of peritoneal mesothelioma has evolved dramatically in the past two decades. While the disease remains challenging, multimodal treatment strategies now offer hope for extended survival and improved quality of life for many patients.

Treatment Modality	Approach/Method	Outcome/Survival	Source
Cytoreductive Surgery (CRS)	Complete removal of visible tumor	Mainstay; crucial for cure	3,4,7,14,15,16
HIPEC (Heated Intraperitoneal Chemotherapy)	Chemotherapy delivered directly into abdomen during surgery	Improves survival; 5-year survival up to 70% in selected cases	3,4,7,14,15,16
EPIC/NIPEC (Early/Postoperative Intraperitoneal Chemotherapy)	Additional chemo post-surgery	Further survival benefit	14,15
Systemic Chemotherapy	Pemetrexed + cisplatin or raltitrexed	Palliative; median survival 12–14 months	4,7,16
Targeted Therapy	ALK inhibitors (select cases); angiokinase inhibitors, anti-VEGF	Experimental; promising for select molecular subtypes	12,16
Immunotherapy	Immune checkpoint inhibitors	In trials; emerging option	16
Palliative Care	Symptom control, supportive care	Improves quality of life	7

Table 4: Treatment Approaches and Outcomes

Multimodal Treatment: Surgery and Intraperitoneal Chemotherapy

The combination of cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is now considered the standard of care for eligible patients. The goal of CRS is to remove all visible tumor deposits within the abdominal cavity. HIPEC is then administered directly into the peritoneum, using heated chemotherapy agents (commonly cisplatin and doxorubicin) to kill microscopic residual cancer cells 3,4,7,14,15,16.

• Survival Impact: Median survival with this approach has improved dramatically, from about 1 year with supportive care alone to 3–5 years or longer. Five-year survival rates can reach as high as 70% in selected patients who undergo complete cytoreduction and adjuvant intraperitoneal chemotherapy 14,15,16.

• Additional Chemotherapy (EPIC, NIPEC): Early postoperative or long-term intraperitoneal chemotherapy can provide further benefit, especially in high-risk or recurrent cases 14,15.

Systemic Chemotherapy

For patients who are not candidates for surgery or HIPEC, systemic chemotherapy remains an option, primarily for palliation. The most effective regimens are based on those used for pleural mesothelioma, such as pemetrexed and cisplatin. However, these regimens offer only modest improvements in survival (median 12–14 months) 4,7,16.

Targeted and Novel Therapies

• ALK Inhibitors: For the small subset of patients with ALK rearrangements, ALK inhibitor drugs may offer a personalized, effective therapy 12,16.
• Angiokinase Inhibitors & Anti-VEGF Therapy: Agents like nintedanib and bevacizumab have shown some benefit in clinical trials when combined with chemotherapy 16.
• Immunotherapy: Immune checkpoint inhibitors are under investigation and may lead to future advances, particularly for patients with specific molecular features 16.

Supportive and Palliative Care

Regardless of treatment intent, managing symptoms such as pain, ascites, and nutritional problems is critical to maintaining quality of life. Palliative care teams play a key role throughout the disease course 7.

Prognostic Factors

Survival outcomes depend heavily on:

• Completeness of cytoreductive surgery
• Disease volume at diagnosis
• Patient age and gender (women fare better)
• Molecular and histological subtype 2,3,14,15

Conclusion

Peritoneal mesothelioma, though rare, is a complex and formidable disease. Recent advances in diagnosis and treatment have brought new hope, but early recognition and specialized care remain essential for optimal outcomes.

Key Points:

• Symptoms are often vague and include abdominal pain, swelling, weight loss, and fatigue, making early diagnosis challenging.
• Types include diffuse malignant, localized, and several histopathological and molecular subtypes, each with unique behaviors and prognoses.
• Causes are most strongly linked to asbestos exposure, with genetic and rare environmental factors playing a role in certain cases.
• Treatment now centers on cytoreductive surgery and HIPEC, with emerging roles for targeted therapies and immunotherapy. Multimodal approaches have significantly improved survival for many patients.

If you or a loved one is facing peritoneal mesothelioma, seeking care at a specialized center with experience in this rare disease can make a crucial difference. Early detection, multidisciplinary management, and access to evolving therapies are key to improving both survival and quality of life.