Reactivity with the EpCAM-specific antibodies MOC-31 and Ber-Ep4 in plasma cell neoplasms: a potential diagnostic pitfall in cytology samples

Objective: Epithelial cell adhesion molecule (EpCAM) is a protein expressed on surfaces of healthy epithelia, and is overexpressed in dysplasias and carcinomas. Immunohistochemistry (IHC) utilizing antibodies that react with EpCAM, such as MOC-31 and Ber-EP4, distinguish reactive mesothelial cells from carcinomas in serous effusions. IHC is crucial in effusions with singly dispersed atypical cells, a scenario with a broad differential, including hematopoietic malignancies. Plasma cell neoplasms (PCN) are the second most common hematopoietic malignancy, manifesting as multiple myeloma or plasmacytoma, with 6% of cases developing serous cavity involvement. Most PCNs are readily recognizable; however, variants that deviate from the classic cytomorphology risk erroneous diagnosis. This study demonstrates EpCAM expression in a subset of PCNs, highlighting a potential diagnostic pitfall in serous effusion cytology. Methods: A 10-year retrospective search for cytology specimens with a diagnosis of PCN was performed. All cases demonstrating CD138/CD38 and monoclonal immunoglobulin expression, and adequately cellular cell block were included. IHC analysis for MOC-31 and Ber-EP4 was performed using Ventana Benchmark Ultra. Scoring was performed as follows: total IHC score equals the positive proportion (0 = no positive tumor cells; 1 = <1%; 2 = 1–10%; 3 =11–33%; 4 = 34–66%; 5 = 67–100%) plus staining intensity (0, no staining; 1, weak; 2, moderate; 3, strong). A score > 4 was considered positive. Results: 2 of 28 (7%) PCNs demonstrated positivity for MOC-31 and Ber-Ep4. Conclusion: A subset of PCNs in cytology samples show positivity for MOC-31 and Ber-EP4 which could result in misinterpretation as carcinoma.