The utility of claudin‐4 versus MOC‐31 and Ber‐EP4 in the diagnosis of metastatic carcinoma in cytology specimens.

Background: Claudin‐4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin‐4 versus MOC‐31 and Ber‐EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. Methods: This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine‐needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin‐4 and compared with those previously stained for MOC‐31 and Ber‐EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases). Results: None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin‐4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC‐31 and Ber‐EP4, claudin‐4 had the highest specificity and PPV (100% for each), followed by Ber‐EP4. Claudin‐4 showed high sensitivity (93.7%), albeit lower than MOC‐31. MOC‐31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber‐EP4 had the lowest sensitivity (91.6%). Conclusions: Claudin‐4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC‐31 and Ber‐EP4. Mesothelial lineage can be ruled out when claudin‐4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin‐4 and Ber‐EP4 results in the highest combined sensitivity and specificity. The findings in this study demonstrate the high sensitivity and superior specificity of claudin‐4 as a single marker for carcinoma in cytology specimens and its ability to rule out mesothelial lineage with high certainty. The authors also identify the highly sensitive and specific combination of claudin‐4 and Ber‐EP4 in diagnosing equivocal specimens previously categorized as atypical or suspicious. [ABSTRACT FROM AUTHOR]