Pleural effusion cytology has been widely used in the investigation of pathologic fluid accumulation in pleural spaces. However, up to one-tenth of the cases were not given a definitive diagnosis. These cases have largely been neglected in the bulk of the literature.


To provide real-world data on indefinite diagnoses including “atypia of uncertain significance” (AUS) and “suspicious for malignancy” (SFM) in pleural effusion cytology and to investigate pathologists’ practice patterns on using these diagnostic categories.


We reported the diagnoses of 51 675 cases. Descriptive statistics and correlation coefficients were used to analyze the relationships between different diagnostic categories and pathologists’ practice patterns and possible explanatory variables.


The diagnoses AUS and SFM were reported in 4060 cases (7.86%) and 1554 cases (3.01%) in the cohort, respectively. The mean rates for these indefinite diagnoses varied up to 3-fold between pathologists. Correlations were found between AUS and SFM, as well as between indefinite diagnoses and negative for malignancy (NFM). No correlations were found between pathologists’ years of experience or case volume and the rates of indefinite diagnosis or diagnostic certainty.


A real-world baseline for the rates of indefinite diagnoses in pleural effusion cytology is provided in this large retrospective study. Pathologists show significant variation in their use of indefinite diagnostic categories, and the tendency to use these ambiguous terms was not correlated with individuals’ experience or case volume. How to untangle the intertwined relationship between the uncertainty of indefinite diagnoses and that of NFM requires future prospective studies.

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Competing Interests

The authors have no relevant financial interest in the products or companies described in this article.

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