Approach to Diagnostic Cytopathology of Serous Effusions

Our plain-English summary of Approach to Diagnostic Cytopathology of Serous Effusions, by V.B. Shidham, L.J. Layfield (CytoJournal, 2021).

The study

• Authors: V.B. Shidham, L.J. Layfield
• Journal: CytoJournal
• Published: 2021;18:32
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2021 Cytopathology Foundation Inc, Published by Scientific Scholar.

In plain English

This article is a review that forms part of a cytopathology book series. It did not report a new study of patients and did not discuss asbestos exposure. The authors described how pathologists should process and interpret fluid drained from effusions around the lungs, abdomen and heart. They wrote that, except in high-grade cancers, the usual single-cell signs of cancer do not apply to most effusion specimens, partly because reactive mesothelial cells can look much like cancer cells. Finding a 'second foreign population' of cells besides mesothelial and inflammatory cells was described as generally consistent with cancer that has spread. For mesothelioma, the authors wrote that most cells show little atypia beyond larger size. The clues they named were many scattered mesothelial-type cells and many large three-dimensional groups. They recommended preparing a cell-block for immunostaining when cancer is suspected, using a five-tier reporting system, and being conservative to avoid false positive reports. The authors concluded that understanding pitfalls would increase diagnostic accuracy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review (book chapter published as a review article); no original data
• Who was studied: No study population. The article discusses cytologic evaluation of serous effusion fluids (pleural, peritoneal and pericardial) in general, illustrated with example specimens.
• Main results:
  • The authors stated that, except for high-grade neoplasms, standard single-cell criteria of malignancy are not applicable to most effusion cytology specimens.
  • The authors described reactive mesothelial cells as a consistent component of effusion fluids that may overlap in appearance with malignant cells.
  • The authors described a 'second foreign population' of cells, other than mesothelial and inflammatory cells, as generally consistent with metastatic neoplasm.
  • For mesothelioma, the authors wrote that most cells lack marked atypia apart from increased size. They named the clues as quantitative (numerous scattered mesothelial-lineage cells in a hypercellular smear) and qualitative (many large three-dimensional groups).
  • The authors wrote that the non-cohesive solitary cells of epithelioid-type mesothelioma may resemble different types of carcinoma, such as renal cell carcinoma.
  • The authors recommended routinely preparing a cell-block for immunocytochemistry when the clinical history suggests cancer.
  • The authors recommended a five-tier reporting system: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and positive for malignancy.
  • Because a positive result implies late disease and palliative rather than curative management, the authors recommended a conservative approach to avoid false positives.
  • On specimen handling, the authors recommended sending the entire collected fluid volume, up to 1000 ml, with at least 50 ml so that cell-blocks can be prepared. They said specimens may be refrigerated at 4°C for up to 24 hours before processing.
• The authors' conclusion: The authors concluded that understanding potential pitfalls at every stage, from processing to ancillary studies, would increase diagnostic accuracy and reduce atypical interpretations and false positive results.
• Limitations the authors state:
  • The authors noted that diagnostic criteria for the atypical and suspicious reporting categories have not been methodically studied and vary between institutions and observers.

Topics

Medical terms in this study, explained in our Lexicon: Cytology, Serous Fluid, Pathology, Fluid Cytology, Collagen, Reactive Mesothelial Hyperplasia, Fine-Needle Aspiration, Adenocarcinoma.

Related studies

• Practical Approach to Reporting Based on the International System for Serous Fluid Cytopathology — E. Viljanen, I. Kholová, et al. (2025)
• Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions — I. Cozzi, F.A. Oprescu, et al. (2018)
• Diagnostic problems in serous effusions — C.W. Bedrossian (1998)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Diagnostic accuracy of calretinin for malignant mesothelioma in serous effusions: a meta-analysis — D. Li, B. Wang, et al. (2015)
• Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions — A.F. Lauritzen (1989)

Browse more research in CytoJournal, or return to medical research.