The role of an immunohistochemical panel including CD45, CK5/6, and ER in classifying challenging breast lesions in Iraqi pathology.

Accurate diagnosis of breast lesions is often complicated by the morphological overlap between benign, pre-malignant, and malignant entities on hematoxylin and eosin (H&E) stained sections. This study evaluated the diagnostic utility of an immunohistochemical (IHC) panel, comprising Estrogen Receptor (ER), Cytokeratin 5/6 (CK5/6), and Leukocyte Common Antigen (CD45), in resolving these diagnostic ambiguities among Iraqi patients. The panel was designed to differentiate epithelial (ER, CK5/6) and lymphoid (CD45) lineages, enabling the distinction between benign, pre-malignant, and malignant processes. A retrospective cross-sectional analysis was performed on 120 challenging breast lesions where the initial H&E diagnosis was inconclusive. Statistical performance was assessed using sensitivity, specificity, and accuracy metrics, with significance determined at p < 0.05. The IHC panel resulted in the reclassification of 53 cases (44.2%), with the highest reclassification in ADH (72.0%). The combined panel demonstrated 91.1% sensitivity, 93.3% specificity, and 92.5% accuracy (p < 0.001) for differentiating benign from malignant lesions. ER and CK5/6 were decisive in the majority of reclassified cases. In conclusion, the three-marker IHC panel (ER, CK5/6, and CD45) provides a statistically significant improvement in diagnostic accuracy and reliability in challenging breast lesions, reducing diagnostic uncertainty and supporting optimal patient management.