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Phagocytic mesothelial cells are a rare finding that can complicate the diagnosis of serous effusions, especially after allogeneic peripheral blood stem cell transplantation. Differentiation from histiocytic hemophagocytosis is vital. This distinction ensures patients receive correct care, as these conditions imply very different clinical paths. A recent case study published in Diagnostic Cytopathology detailed a patient presenting with fever and dyspnea 18 months post-transplant for chronic active Epstein-Barr virus (EBV) infection.
The patient exhibited mild chronic graft-versus-host disease (GvHD). Initially, cytomorphological examination of the pericardial effusion showed cells containing lymphocyte-like structures and hemosiderin. These appeared similar to phagocytic histiocytes. However, immunocytochemical (ICC) staining was pivotal for a definitive diagnosis. The cells tested positive for pan-cytokeratin (AE1/AE3), calretinin, and desmin. Conversely, they remained negative for CD163, which is a specific marker for histiocytes. This profile confirms their mesothelial origin despite their unusual phagocytic behavior.
Accurate identification of phagocytic mesothelial cells is crucial for avoiding misdiagnosis of systemic syndromes like hemophagocytic lymphohistiocytosis (HLH). In this case, the patient’s EBV DNA levels were undetectable. Furthermore, the ferritin levels were not significantly elevated. These factors, combined with the favorable clinical course, reinforced that the effusion was not caused by a recurrence of EBV or a systemic hyperinflammatory response.
Moreover, clinicians must recognize that reactive mesothelial cells can mimic the activity of the mononuclear phagocyte system. Therefore, utilizing a robust panel of ICC markers is essential. Specifically, calretinin and desmin are excellent markers for confirming mesothelial identity. Meanwhile, CD163 or CD68 helps rule out histiocytic involvement. Consequently, pathologists can provide a precise diagnosis that prevents unnecessary aggressive therapy.
Pathologists use immunocytochemistry. Mesothelial cells typically express calretinin, desmin, and pan-cytokeratin. Histiocytes, however, express markers like CD163 or CD68 and are negative for mesothelial markers.
Mistaking mesothelial cells for histiocytes might lead to an incorrect diagnosis of hemophagocytosis or HLH. This could result in unnecessary and potentially toxic immunosuppressive treatments.
Disclaimer: This content is for informational and educational purposes only... Refer to the latest local and national guidelines for clinical practice.
References
1. Satomi H et al. Phagocytic Mesothelial Cells in Pericardial Effusion Following Allogeneic Peripheral Blood Stem Cell Transplantation for Chronic Active Epstein-Barr Virus Infection: A Distinctive Cytomorphological and Immunocytochemical Case Study. Diagn Cytopathol. 2026 Feb 06. doi: 10.1002/dc.70094. PMID: 41646004.
2. Maruyama R, et al. Phagocytic mesothelial cells in serous effusions. Acta Cytologica. 1998;42(5):1225-1229.
3. Gouda MH. Immunohistochemical Differentiation between Reactive and Malignant Mesothelial Proliferations in Pleural Effusion. Faculty of Medicine, Benha University. 2022.

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