Pericardial effusion cytology: malignancy rates, patterns of metastasis, comparison with pericardial window, and genomic correlates

Introduction

Cytologic evaluation of pericardial fluid is essential for diagnosing malignant pericardial effusions secondary to metastatic disease and for guiding appropriate clinical management; however, large cohort and up-to-date studies on malignancy rates and distribution of primary tumor sites is lacking.

Materials and methods

A retrospective analysis of pericardial fluid specimens from 2 large academic medical centers over a 10-year period was conducted. Clinical and specimen characteristics were correlated with cytologic diagnoses, and compared with surgical pathology pericardial specimens when available. In addition, genomic testing results were examined in a subset of malignant cases.

Results

A total of 1667 pericardial fluid specimens were evaluated, with 15.3% diagnosed as malignant. Lung cancer (50.6%) was by far the most common primary tumor causing malignant pericardial effusions, followed by breast (13.0%), hematolymphoid (12.6%), and gastrointestinal (6.1%) cancers. A subset of patients with paired cytology and surgical pathology pericardial specimens showed concordance in 84.2% of cases, with discordant cases more frequently presenting with a positive cytology but negative surgical pathology result. Genomic analysis of a subset of malignant pericardial effusions revealed the most frequently mutated genes to be TP53, KRAS, CDKN2A/B, and PIK3CA, with a larger proportion of high tumor mutational burden (≥10 muts/Mb) in pericardial fluid samples compared to primary or metastatic sites.

Conclusions

While lung cancer is the most frequent cause of a cytology-confirmed malignant pericardial effusion, familiarity with relative frequencies of metastases from other sites can be particularly helpful, especially in the diagnostic work-up of an occult malignant pericardial effusion.