Malignant pleural effusions for cancer genotyping: A matter of trans-pleural traffic of cell-free tumor DNA

Body cavity fluids accumulating in progressive malignancies are potential subjects of regular clinical testing for cancer-related features. Besides the cellular component, the supernatant of the fluid proved to gain diagnostic impact as the cell-free DNA (cfDNA) fraction ideally reflects general molecular features of the related tumorous process, e.g. in lung carcinoma. Thus, malignant pleural effusions can be used for lung cancer genetic profiling and this might remain the only source for testing in critical cases. The cfDNA concentration of the pleural effusion depends on many factors in both benign and malignant conditions. Further to direct pleural metastatic spread, the redirection of tissue lymphatic circulation, tumor angiogenesis, inflammatory processes and other variables may contribute to or enhance the enrichment of the effusion tumor DNA from the earliest stages of carcinogenesis. Our review addresses the traffic of cfDNA in the pleural space and the diagnostic utility of effusion cfDNA from the perspective of the complex pleural pathophysiology.

Automated summary

Fluid accumulating in progressive malignancies can be tested for cancer-related features, with the cell-free DNA fraction reflecting molecular characteristics of the tumor process. Pleural effusions can be used for genetic profiling in lung cancer, with the concentration of cfDNA depending on various factors in benign and malignant conditions. The enrichment of effusion tumor DNA may be influenced by factors such as pleural metastasis, tumor angiogenesis, and inflammatory processes.