What labs and tests are used to diagnose mesothelioma?

Diagnostic Tests for Mesothelioma

The diagnosis of malignant pleural mesothelioma (MPM) requires a comprehensive approach including occupational history, imaging studies, and pathological confirmation through biopsy, with thoracoscopy being the preferred method for obtaining tissue samples. 1

Initial Diagnostic Workup

History and Basic Tests

• Occupational history with emphasis on asbestos exposure is essential as asbestos is a well-established etiological factor for MPM, documented in 70-80% of cases 1
• General laboratory blood tests including hemoglobin, leukocytes, platelets, and basic biochemistry should be performed 1
• High white blood cell count, high platelet count (thrombocytosis), and low hemoglobin are associated with poor prognosis 1, 2

Imaging Studies

• Contrast-enhanced CT scan of the chest and upper abdomen is the recommended initial imaging for diagnosis and staging 1
• Chest X-ray is typically the first imaging study but lacks sufficient sensitivity and specificity for definitive diagnosis 1
• FDG-PET/CT should be obtained for initial staging in patients being considered for treatment, as it provides superior diagnostic specificity and sensitivity compared to CT or MRI alone 1, 3
• MRI (preferably with IV contrast) may be used to further assess invasion of the tumor into the diaphragm, chest wall, and mediastinum 1, 4

Pathological Diagnosis

Pleural Fluid Analysis

• Thoracentesis with cytological examination of pleural effusion can be diagnostic but often shows equivocal results 1
• Effusion cytology for definitive MPM diagnosis remains controversial, and biopsy is recommended especially for histological subtyping 1

Biopsy Techniques

• Thoracoscopy is the preferred method for obtaining tissue samples 1
• Biopsy sampling of at least three distant sites is recommended for robust subtyping and grading 1
• CT-guided needle biopsy can be used but has a lower success rate (92%) compared to thoracoscopic pleural biopsy (100%) 3, 5
• Video-assisted thoracoscopy or open pleural biopsy may be needed to provide sufficient material for accurate histological diagnosis 1, 5

Histopathological Analysis

• Immunohistochemistry (IHC) is recommended for all primary diagnoses of MPM 1
• For epithelioid subtype, at least two 'mesothelial' markers and at least two '(adeno)carcinoma' markers should be used 1
• For sarcomatoid subtype, cytokeratin staining should be used 1
• Loss of BAP1 and/or MTAP as surrogate for CDKN2A deletion aid in MPM diagnosis 1

Advanced Diagnostic Methods

Molecular Testing

• Loss of BAP1 (more common in epithelioid subtype) and/or loss of CDKN2A (more common in sarcomatoid subtype) are important molecular markers 1, 6
• Tumor genomic sequencing is currently done on a research basis and is not recommended for routine clinical use 1
• BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1, and DDX51 are frequently mutated genes in MPM 1

Biomarkers

• Circulating tumor markers alone cannot adequately distinguish MPM 1
• Soluble mesothelin-related protein (SMRP) has been studied as a potential biomarker but lacks sufficient sensitivity and specificity 1
• Other biomarkers such as osteopontin (OPN) and Fibulin-3 (FBLN3) have been investigated but are not recommended for routine diagnosis 1

Staging Procedures

Additional Imaging for Staging

• For surgical candidates, additional staging investigations may be required 1
• PET-CT is important to exclude metastases in surgical candidates 1
• Dedicated abdominal (+/- pelvic) CT scan with IV and oral contrast should be considered if abnormalities suggesting metastatic disease are observed on chest CT or PET/CT 1

Invasive Staging Procedures

• Mediastinal staging by endobronchial ultrasound (EBUS) or mediastinoscopy should be considered for surgical candidates to exclude contralateral involvement 1
• Mediastinoscopy is recommended in case of potentially resectable disease if EBUS is negative despite fluorodeoxyglucose-avid lymph nodes 1
• Laparoscopy may be needed in selected cases to rule out transdiaphragmatic extension 1

Common Pitfalls and Caveats

• Relying solely on pleural fluid cytology may lead to missed or incorrect diagnoses; biopsy is essential for definitive diagnosis 1, 5
• Inadequate sampling can lead to misclassification of histological subtypes, affecting treatment decisions and prognosis 1
• Molecular testing should not be used in isolation as the field is still evolving 1
• The interval within which pre-treatment assessment should be finalized should be as short as possible to avoid treatment delays 1
• Recent (<1 month) imaging studies should be available prior to invasive procedures 1