Malignant Mesothelioma: Asbestos-Related Cancer of the Pleura and Peritoneum — Overview, Diagnosis & Treatment Options | MyMedicPlus

Malignant mesothelioma is a rare but aggressive cancer arising from the mesothelial cells lining the pleura (most common, approximately 80%), peritoneum (approximately 10-15%), pericardium, and tunica vaginalis. Approximately 3,000 new US cases are diagnosed annually. Asbestos exposure is the primary cause of pleural mesothelioma, with a 20-50 year latency period. Three histological subtypes exist: epithelioid (best prognosis, approximately 60%), sarcomatoid (worst prognosis, approximately 20%), and biphasic (mixed, approximately 20%).

Asbestos exposure (crocidolite greater than amosite greater than chrysotile) is the dominant cause of pleural mesothelioma, responsible for 70-80% of cases with a 20-50 year latency period. SV40 virus was proposed as a co-carcinogen but evidence remains inconclusive. Erionite fiber exposure (Turkey, North Dakota) causes mesothelioma without asbestos. BAP1 germline mutations cause hereditary mesothelioma predisposition. Peritoneal mesothelioma has a weaker asbestos association (approximately 30-40%) and is more common in women and younger patients than pleural disease. Prior therapeutic radiation is a rare cause.

Pleural mesothelioma presents insidiously with progressive dyspnea (from pleural effusion) and pleuritic chest wall pain, which becomes persistent and severe. Dry cough, fatigue, and weight loss are common. Clubbing may occur. Pleural effusion on chest X-ray prompts thoracentesis; cytology is positive for malignancy in approximately 50% of cases. Peritoneal mesothelioma presents with abdominal distension (from ascites), diffuse abdominal pain, nausea, early satiety, new-onset hernia, and weight loss. Diagnosis is often delayed as symptoms mimic common benign conditions.

CT of chest, abdomen, and pelvis characterizes disease extent. MRI better defines chest wall invasion. Video-assisted thoracoscopic surgery (VATS) with pleural biopsy is the preferred diagnostic approach for pleural mesothelioma. IHC panel: calretinin, WT1, D2-40, and CK5/6 positive; CEA, B72.3, MOC-31, and BG8 negative for mesothelioma versus carcinoma. BAP1 IHC loss and CDKN2A (p16) FISH deletion support malignant diagnosis. Eighth edition AJCC TNM staging for pleural mesothelioma uses T (local extent), N (nodal), M (distant). IMIG staging is also used.

Unresectable pleural mesothelioma: nivolumab plus ipilimumab (CheckMate 743, first-line preferred); cisplatin plus pemetrexed plus bevacizumab (alternative); cisplatin plus pemetrexed (standard backbone chemotherapy). Selected resectable epithelioid patients: extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) plus adjuvant or neoadjuvant chemotherapy and radiation (trimodality therapy). P/D is preferred over EPP at most centers due to better quality of life. Peritoneal mesothelioma: cytoreductive surgery (CRS) plus HIPEC (cisplatin) for eligible patients with good performance status; pemetrexed-based chemotherapy for unresectable disease.

Pleural mesothelioma median OS with immunotherapy (nivolumab plus ipilimumab): 18.1 months overall; non-epithelioid histology benefits most (18.1 vs 8.8 months with chemotherapy). Epithelioid histology 3-year OS: approximately 28% with immunotherapy. Sarcomatoid and biphasic mesothelioma have worse prognosis (median OS 8-10 months). Peritoneal mesothelioma with CRS plus HIPEC: median OS 3-5+ years for selected patients with complete cytoreduction, significantly better than pleural mesothelioma. Prognostic factors: histological subtype, completeness of cytoreduction, BAP1 status, and performance status.

Complete elimination of asbestos use is the definitive prevention strategy, already achieved in many high-income countries. Asbestos workers require regular medical surveillance (chest X-ray or low-dose CT, pulmonary function testing). BAP1 germline mutation carriers should undergo annual whole-body MRI, ophthalmology screening for uveal melanoma, and dermatology surveillance for cutaneous melanoma. Workers in occupations with historical asbestos use (shipbuilding, construction, insulation) should disclose exposure history to their physicians. No validated biomarkers exist for early detection screening in high-risk populations.