Ancillary studies in pleural, pericardial, and peritoneal effusion cytology

Our plain-English summary of Ancillary studies in pleural, pericardial, and peritoneal effusion cytology, by K.E. Sundling, E.S. Cibas (Cancer Cytopathology, 2018).

The study

• Authors: K.E. Sundling, E.S. Cibas
• Journal: Cancer Cytopathology
• Published: 2018;126 Suppl 8:590-598
• Type of article: Review
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural, pericardial, and peritoneal effusion specimens present diagnostic challenges and clinical opportunities for cytology. For the patient, these specimens may be the first diagnosis of malignancy or the first sign of disease recurrence. This review aims to provide useful approaches with which to resolve key difficulties in cytologic diagnosis through the use of ancillary studies, focusing on immunohistochemistry. These approaches are suggested in concert with clinical, radiographic, and morphologic findings. The differentiation of reactive mesothelial cells from malignant mesothelioma and adenocarcinoma is a recurring theme, and Wilms tumor 1 (WT1)/AE1/AE3, claudin 4, and BRCA1-associated protein 1 (BAP1) immunostains are useful new tools in the armamentarium. A targeted workup is suggested for patients with no known primary site or with multiple prior malignancies. Molecular and other biomarker testing can be performed on even modestly cellular fluid specimens and may allow patients to benefit from targeted therapy without the need for additional tissue biopsies. Cancer Cytopathol 2018;000:000-000. © 2018 American Cancer Society.

© 2018 American Cancer Society.

In plain English

This was a review of ancillary tests, mainly immunohistochemical stains, on fluid around the lungs (pleural), heart (pericardial) and abdomen (peritoneal). It reported no new patient data, only published studies and the authors' practice. A recurring theme was separating reactive mesothelial cells from malignant mesothelioma and adenocarcinoma. A combined WT1/AE1/AE3 stain, they wrote, usually suffices alone to separate mesothelial from epithelial cells. They wrote that claudin 4 outperforms older adenocarcinoma markers; a cited study found no membranous claudin 4 staining in 75 malignant mesotheliomas. They described BAP1 staining as present in benign mesothelial cells but absent in over half of malignant mesotheliomas. They cautioned that benign cells can show patchy BAP1 staining. They noted that malignant mesothelioma is difficult to diagnose with certainty from fluid, except perhaps when a patient with a robust asbestos exposure history, recurrent pleural effusions and characteristic imaging findings has a clearly malignant effusion with abundant large cell clusters of mesothelial type. The authors concluded that targeted stain panels, combined with clinical and morphologic features, give more specific diagnoses and may avoid more invasive tissue sampling.

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 of ancillary studies (mainly immunohistochemistry) in effusion cytology
• Who was studied: No study population; a review of published literature and the authors' practice concerning pleural, pericardial, and peritoneal effusion specimens
• Exposure: No exposure was studied. Asbestos exposure is mentioned only as part of the clinical history that may guide the diagnostic workup.
• Main results:
  • The authors stated that the WT1/AE1/AE3 dual stain is, in most cases, sufficient on its own to tell mesothelial cells from epithelial cells.
  • From cited literature: WT1 staining is reported as positive in approximately 70% to 95% of cases with cells of mesothelial origin.
  • Claudin 4 was described as having better sensitivity and specificity than Ber-EP4 and MOC-31 for distinguishing adenocarcinoma from mesothelial cells.
  • From a cited study: no membranous claudin 4 staining was found in 75 malignant mesotheliomas, although 11% (8 of 75 cases) had weak cytoplasmic staining, which is considered nonspecific.
  • BAP1 is expressed in the nuclei of benign mesothelial cells but is absent in more than half of cases of malignant mesothelioma (from cited literature).
  • The authors cautioned that patchy BAP1 staining may be seen in benign and reactive mesothelial cells.
  • From a cited study of patients with malignant mesothelioma: karyotyping combined with 9p21 and 22q deletion testing by FISH detected diagnostic abnormalities in approximately 54% of patients (13 of 24 patients).
  • The authors stated that malignant mesothelioma is difficult to diagnose with certainty on cytology, except perhaps when a patient with a robust asbestos exposure history, recurrent pleural effusions and characteristic radiographic findings has a clearly malignant effusion.
  • In that possible exception, the malignant effusion also has abundant large (mulberry-like) cell clusters with a mesothelial immunophenotype (a staining pattern typical of mesothelial cells).
• The authors' conclusion: The authors concluded that targeted panels of immunohistochemical stains, combined with clinical and morphologic features, provide more specific diagnoses and may eliminate the need for more invasive tissue sampling.
• Limitations the authors state:
  • The authors did not cover cell block preparation methods in detail.
  • The authors noted that very few data exist on reporting PD-L1 in specimens with fewer than 100 well-preserved tumor cells.

Topics

Medical terms in this study, explained in our Lexicon: Pericardial, Cytology, Immunohistochemistry, Reactive Mesothelial Cells, Malignant Mesothelioma, Adenocarcinoma, Wilms Tumor 1 (WT-1), BAP1.

Related studies

• Morphologic and immunocytochemical performances of effusion cell blocks prepared using 3 different methods — X. Jing, Q.K. Li, et al. (2013)
• The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: an institutional experience — E.D. Rossi, T. Bizzarro, et al. (2015)
• Cytomorphological profile of neoplastic effusions: an audit of 10 years with emphasis on uncommonly encountered malignancies — S. Gupta, P. Sodhani, et al. (2012)
• Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers — B. Davidson, B. Risberg, et al. (1999)
• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)

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