Cytokeratins in papillary lesions of the breast: is there a role in distinguishing intraductal papilloma from papillary ductal carcinoma in situ?

We studied 50 papillary lesions (25 papillomas and 25 papillary ductal carcinomas in situ, DCIS) diagnosed at Singapore General Hospital, for immunohistochemical expression of cytokeratin (CK) 5/6, CK14, and 34betaE12. The immunoscore (proportion of stained cells multiplied by staining intensity) was compared between the two groups. Cytokeratin expression was corroborated by confocal microscopy. Results were applied to a separate series of 43 papillary tumors from Hong Kong (HK). CK5/CK6, CK14, and 34betaE12 showed higher immunoscores in papillomas (mean values, 107.6, 186.6, and 113.1, respectively) than papillary DCIS (mean values, 12, 29.6, and 34.5, respectively; P<0.0001, P<0.001, and P<0.02, respectively). A cutoff immunoscore threshold of 50 appeared discriminatory between papilloma and papillary DCIS, and this value was applied to the HK cases, with CK5/CK6, CK14, and 34betaE12 correctly predicting 25 (89.3%), 26 (92.9%), and 27 (96.4%), respectively, of 28 HK lesions labeled as papillomas; while they corroborated 13 (86.7%), 13 (86.7%), and 5 (33.3%), respectively, of 15 HK cases diagnosed as papillary DCIS. Review of discordant cases showed that lesions were small, derived from core biopsies, or disclosed accompanying invasive carcinoma. When both SGH and HK cases were combined as a group, the sensitivity of an immunoscore of 50 or less in the diagnosis of papillary DCIS was 95%, 85%, and 62.5% for CK5/CK6, CK14, and 34betaE12, respectively, while the specificity was 86.8%, 94.3%, and 86.8%, respectively. CK immunohistochemistry can aid in evaluating papillary breast lesions. 34betaE12 does not appear as useful in identifying papillary DCIS.