Approach to Diagnostic Cytopathology of Serous Effusions
Authors: Shidham Vinod B. , Layfield Lester J. 
Published: January 2022

Collection of most serous fluids from various effusions is a relatively simple procedure. Because of this, serous fluids are commonly submitted for pathologic examination including cytopathologic evaluation by various clinical institutions. As a consequence, even a general pathology laboratory which may not have expertise with highly trained cytopathologist would be confronted with serous fluids for cytologic evaluation.
However, cytopathologic evaluation of serous fluids is complex as compared to evaluation of fine needle aspiration cytology. This signifies the fact that all pathologists, irrespective of subspeciality cytopathology training and level of subspeciality expertise, should be conversant with the diagnostic challenges and pitfalls of effusion fluid cytology.
Although, majority of effusions are due to reactive and non-neoplastic etiologies, cancer is one of the causes of an effusion as a manifestation of advanced cancer. Detecting neoplastic cells in effusion specimens in most of clinical settings is related to the advanced status of the disease, which usually is equivalent to incurable stage. Thus, interpretation of cytopathology as positive for cancer cell is highly critical in planning the trajectory of the clinical management with an obvious negative impact of false positive interpretation.
Apart from cancer, effusions may be secondary to hemodynamic pathologies such as heart failure, hypoalbuminemia, cirrhosis etc. in addition to the different inflammatory conditions including parasitic infestations, bacterial, fungal, or viral infections, and other non-neoplastic etiologies including collagen diseases. Due to the cytomorphologic overlap of reactive mesothelial cells with malignant cells, general cytologic criteria for diagnosis of malignancy in single cells cannot be applied in most of the effusion specimens. This challenge is further amplified because of surface tension related phenomenon which ‘round up’ the cells after exfoliation in serous fluids. As a result, the native shapes of cancer cells cannot be a guiding feature. Thus the cytomorphologic features of cancer cells in serous fluids may not be same as seen in routine cytopathology of exfoliative, brushing, and fine-needle aspiration specimens.
The cancer cells may continue to proliferate after exfoliation in the nutrient rich effusion fluids and may form proliferation spheres. It is crucial to consider these factors when interpreting effusion cytology. Amongst malignant effusions, adenocarcinomas are the most common cause of metastatic cancers, but almost any type of malignancy including melanomas, hematopoietic neoplasms, sarcomas, and mesotheliomas may involve serous cavities. The interpreter must be aware of the wide range of the cytomorphologic appearances of reactive mesothelial cells in effusion fluids. It is essential to understand these and other nuances related to effusion fluid cytology. Understanding potential pitfalls during various stages from processing to application of ancillary studies would increase the diagnostic accuracy and minimize atypical interpretations and false positivity.