Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma

Background: We retrospectively analyzed hyaluronic acid (HA) concentrations in pleural fluid and evaluated its utility for the differential diagnosis of malignant pleural mesothelioma (MPM).

Methods: Pleural fluid HA concentrations were measured in 334 patients, including 50, 48, 85, 18, 86, 6, and 41 patients with MPM, benign asbestos pleurisy (BAP), lung cancer (LC), other malignant conditions (OMCs), infectious pleuritis (IP), collagen disease (CD), and other conditions, respectively.

Results: The median (range) HA concentrations in pleural fluid were 78,700 (7920-2,630,000)ng/ml in the MPM group, 35,950 (900-152,000)ng/ml in the BAP group, 19,500 (2270-120,000)ng/ml in the LC group, 14,200 (900-101,000)ng/ml in the OMC group, 23,000 (900-230,000)ng/ml in the IP group, 24,600 (9550-80,800)ng/ml in the CD group, and 8140 (900-67,800)ng/ml in the other diseases group. HA levels were significantly higher in the MPM group than in the other groups. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve value of 0.832 (95% confidence interval, 0.765-0.898) for the differential diagnosis of MPM. With a cutoff value of 100,000ng/ml, the sensitivity and specificity were 44.0 and 96.5%, respectively. In the MPM group, HA values were significantly higher for the epithelioid subtype than for the sarcomatous subtype (p=0.007), and higher in earlier stages (I and II) than in advanced stages (III and IV) (p=0.007).

Conclusions: A diagnosis of MPM should be strongly considered in patients with pleural fluid HA concentrations exceeding 100,000ng/ml.