What is the role of Immunohistochemistry (IHC) in differentiating between benign and malignant papillary lesions of the breast?

Role of Immunohistochemistry in Papillary Lesions of the Breast

Immunohistochemistry (IHC) plays a crucial role in differentiating between benign and malignant papillary lesions of the breast, significantly improving diagnostic accuracy and reducing observer variability.

Key Immunohistochemical Markers for Papillary Lesions

• Myoepithelial Markers: Essential for distinguishing benign papillomas (which typically show a continuous layer of myoepithelial cells) from papillary carcinomas 1

• p63: The preferred myoepithelial marker due to its nuclear staining pattern, minimal cross-reactivity, and high sensitivity 1

• Basal Cytokeratins (CKs): Useful for differentiating various types of epithelial hyperplasia within papillary lesions 1

• CK5/6: Considered the best marker for identifying usual hyperplasia, which shows a characteristic mosaic staining pattern 1

• Neuroendocrine Markers: Chromogranin A and synaptophysin may be positive in papillary carcinomas, particularly in the solid type 1

Diagnostic Approach for Papillary Lesions

Initial Assessment

• Core needle biopsy (CNB) specimens should be evaluated with H&E staining first 2
• For challenging cases, a panel of IHC markers should be applied 1, 3

Recommended IHC Panel

• Myoepithelial markers: p63, calponin 3
• Epithelial markers: CK5/6 3
• Neuroendocrine markers: Chromogranin A, synaptophysin (when solid papillary carcinoma is suspected) 1

Impact of IHC on Diagnostic Accuracy

• Observer agreement on H&E sections alone in papillary core biopsies is only 44% (unweighted kappa = 0.54) 3

• IHC significantly increases agreement to 91% (unweighted kappa = 0.91) 3

• The main effect of IHC is reducing the use of intermediate diagnostic categories and allowing more definitive diagnosis 3

• IHC may decrease the upgrade-to-malignancy rate for benign papillary lesions after ultrasound-guided 14-gauge CNB 2

Diagnostic Challenges and Limitations

• Despite improved accuracy with IHC, misdiagnosis can still occur, suggesting that IHC cannot completely replace surgical excision for definitive diagnosis of benign papillary lesions 2

• Papillary lesions with overlapping features remain challenging even with IHC 4

• There is controversy regarding the presence of a complete myoepithelial cell layer around intracystic papillary carcinomas 1

• Recognition of low nuclear grade atypia within benign papillary lesions and its classification into atypia or in situ carcinoma may pose diagnostic challenges 4

Clinical Implications and Recommendations

• A panel approach using CK5/6, p63, and neuroendocrine markers is recommended for problematic papillary lesions 1

• Complete removal of the lesion remains the treatment of choice for definitive diagnosis, as experience with these markers is still limited 1

• Difficult cases should trigger consensus opinion or expert referral 4

• Judicious use of IHC is recommended to preserve tissue for potential additional studies 5

Pitfalls to Avoid

• Relying solely on IHC without re-evaluation of histological findings on H&E stain 5

• Failing to consider the clinicopathological correlation of each case 5

• Using IHC indiscriminately rather than in targeted situations where it adds diagnostic value 5