What is the difference between peritoneal carcinomatosis and mesothelioma in terms of diagnosis, treatment, and management?

Difference Between Peritoneal Carcinomatosis and Mesothelioma

Peritoneal carcinomatosis and peritoneal mesothelioma are fundamentally different diseases: carcinomatosis represents metastatic spread of cancer from another primary site (most commonly gastrointestinal or ovarian), while peritoneal mesothelioma is a primary malignancy arising from the mesothelial cells lining the peritoneum itself. 1, 2

Origin and Etiology

Peritoneal Carcinomatosis:

• Secondary malignancy representing metastatic spread from a primary tumor elsewhere (colon, rectum, ovary, stomach, appendix) 1
• No specific environmental exposure required
• Occurs as a complication of advanced primary cancer 1

Peritoneal Mesothelioma:

• Primary malignancy of peritoneal mesothelial cells 2, 3
• Accounts for approximately 30% of all mesotheliomas (pleural being most common at 70%) 2
• Strongly associated with asbestos exposure (85% of cases), though can occur in young women without known exposure 2, 4
• Germline BAP1 mutations increase susceptibility 3
• Long latency period of 20-40 years after asbestos exposure 5

Clinical Presentation

Both conditions share overlapping symptoms:

• Ascites, abdominal pain, weight loss, abdominal distension 1, 2, 3

Key distinguishing features:

Peritoneal Mesothelioma specifically presents with:

• Disproportionately small ascites relative to tumor burden (unlike carcinomatosis) 6
• Systemic symptoms including fever and night sweats 4
• Thrombocytemia and hypercoagulability 4
• Dyspeptic complaints may be initial presentation 3

Diagnostic Approach

Critical diagnostic distinction:

For Peritoneal Carcinomatosis:

• Must identify the primary tumor site through comprehensive imaging and endoscopy 1
• CT shows peritoneal nodules, omental caking, typically moderate to large ascites 1, 6
• Cytology and immunohistochemistry directed at identifying primary site (CEA, CA-19-9, CA-125 depending on suspected primary) 1

For Peritoneal Mesothelioma:

• Must exclude other primary tumors first - this is essential to diagnosis 6
• Occupational history of asbestos exposure is critical 5, 3
• CT/ultrasound shows soft-tissue masses, thickened omentum/peritoneum/mesentery, disproportionately small ascites, and may show pleural plaques 6
• Ascitic cytology with immunocytochemistry (calretinin positive, cytokeratin 5/6 positive, Claudin-4 negative, CEA negative) 7, 3
• Tissue biopsy via laparoscopy or CT-guided biopsy is mandatory for definitive diagnosis 3, 6
• Immunohistochemistry must demonstrate mesothelial phenotype and exclude adenocarcinoma 1, 7
• BAP1 loss and CDKN2A/p16 deletion support mesothelioma diagnosis 1, 3

Common pitfall: Cytology alone cannot reliably distinguish reactive mesothelial cells from malignant mesothelioma - tissue biopsy with immunohistochemistry is required 7, 3

Treatment and Management

Peritoneal Carcinomatosis:

• Treatment directed at primary tumor type (colorectal, ovarian, gastric protocols) 1
• For colorectal cancer with isolated peritoneal disease: cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in highly selected patients (PCI <20, complete resection achievable, no extra-abdominal disease) 1
• This remains experimental and should only be performed in specialized centers within clinical trials 1
• For ovarian cancer: HIPEC at interval debulking after neoadjuvant chemotherapy shows proven benefit 8
• Systemic chemotherapy based on primary tumor histology 1

Peritoneal Mesothelioma:

• Standard curative approach: cytoreductive surgery plus HIPEC (using cisplatin and doxorubicin) with 5-year survival rates of 29-63% 2, 9
• Surgery removes bulky tumor, leaving microscopic disease susceptible to intraperitoneal chemotherapy 2, 9
• For unresectable disease: systemic chemotherapy with pemetrexed plus cisplatin (median survival 12-14 months) 2, 3
• Alternative regimen: cisplatin plus irinotecan (CPT-11) with 24% response rate and good tolerability 4
• Rationale for CPT-11: mesothelial cells contain high carboxylesterase levels, activating irinotecan to SN-38 4

Prognosis

Peritoneal Carcinomatosis:

• Prognosis depends entirely on primary tumor type and extent of disease 1
• Generally indicates advanced stage with poor prognosis under systemic chemotherapy alone 1
• Selected patients with limited disease may achieve long-term survival with CRS/HIPEC 1

Peritoneal Mesothelioma:

• Historically dismal prognosis, but dramatically improved with CRS/HIPEC over last two decades 2, 9
• Without aggressive treatment: median survival approximately 12-14 months with chemotherapy alone 2, 3
• With CRS/HIPEC: 5-year survival 29-63% in selected patients 2
• Success requires complete cytoreduction to microscopic residual disease 9

Key Imaging Distinctions

The most useful radiologic clue:

• Peritoneal mesothelioma: disproportionately small ascites relative to tumor burden 6
• Peritoneal carcinomatosis: typically moderate to large ascites 6
• Both show omental caking, peritoneal nodules, and thickened peritoneum 6
• Mesothelioma may show pleural plaques (asbestos exposure marker) 6

Management Algorithm

When encountering peritoneal disease:

1. Obtain detailed occupational history (asbestos exposure suggests mesothelioma) 5, 3
2. Search exhaustively for primary tumor with CT chest/abdomen/pelvis, upper and lower endoscopy, mammography in women 1, 6
3. If primary tumor identified: diagnose as peritoneal carcinomatosis, treat primary tumor 1
4. If no primary tumor found: obtain tissue biopsy (laparoscopy or CT-guided) with immunohistochemistry 3, 6
5. Immunohistochemistry pattern:
   • Mesothelial markers positive (calretinin, cytokeratin 5/6, WT-1) + adenocarcinoma markers negative (CEA, Claudin-4, MOC-31) = mesothelioma 7, 3
   • Adenocarcinoma markers positive = carcinomatosis from occult primary 7
6. If mesothelioma confirmed: refer to specialized center for CRS/HIPEC evaluation 2, 9