Refined Diagnosis of Pleural Effusions by Immunocytochemistry of Cell Blocks

Anticancer Res. 2023 Feb;43(2):669-673. doi: 10.21873/anticanres.16204.


Background/aim: The main objective of microscopic examination of pleural effusions is to ascertain the presence of malignant cells. Effusions prepared routinely using May-Grünwald-Giemsa (MGG)- and Papanicolaou (PAP)-staining can, in a number of cases, provide inconclusive cytological results regarding malignancy.

Patients and methods: This report describes the refined diagnosis of such cases based on immunocytochemical analysis of pleural effusion cell blocks. Of the 340 pleural effusions obtained during 2019 at the Department of Clinical Cytology, Gävle Hospital, Sweden, 63 (18.5%) contained atypical cells of undetermined significance or potentially malignant cells.

Results: This diagnosis could be refined using Epithelial Cell Adhesion Molecule/EPCAM (BEREP4) immunocytochemical analysis of effusion cell blocks, allowing previously inconclusive effusions to be classified as clearly benign 42/63 (66.7%) or malignant 21/63 (33.3%). Effusions initially diagnosed as clearly malignant (27/340; 7.9%) were all 27 (100%) BEREP4-immuno-stained. Most BEREP4-positive effusions (37/48; 77.1%) were also carcinoembryonic antigen (CEA) positive. The number of BEREP4-positive cells, however, tended to exceed that of CEA-positive cells. The BEREP4 positive effusions were further examined using different monoclonal antibodies, such as Thyroid transcription factor 1 (TTF-1) for primary pulmonary adenocarcinoma, to determine the original site of the primary tumour.

Conclusion: Immunohistochemical staining of pleural effusion cell blocks significantly refines the diagnosis of serous pleural effusions, especially in cases where the preliminary diagnosis was atypical cells of undetermined significance or potentially malignant cells. Furthermore, in the cases of malignancy, the origin of the primary tumour could most often be determined.

Keywords: BEREP4; CEA; Pleural effusions; cell block; immunohistochemistry; malignant cells.

MeSH terms

  • Antibodies, Monoclonal
  • Biomarkers, Tumor / metabolism
  • Carcinoembryonic Antigen / analysis
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry
  • Neoplasms* / pathology
  • Pleural Effusion* / diagnosis
  • Pleural Effusion* / pathology
  • Pleural Effusion, Malignant* / diagnosis
  • Pleural Effusion, Malignant* / pathology


  • Carcinoembryonic Antigen
  • Antibodies, Monoclonal
  • Biomarkers, Tumor