Clinicopathologic analysis of breast lesions associated with multiple papillomas

We performed a retrospective clinicopathologic study of 28 patients with breast lesions characterized by the presence of multiple (at least 5) papillomas (MPs) in at least 2 nonconsecutive blocks. All histologic sections were assessed for the presence of coexisting fibrocystic lesions, including atypical hyperplasia (atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH]), lobular carcinoma in situ (LCIS), and papillary atypia (defined as nuclear hyperchromatism, stratification, and architectural complexity of a lesser degree than in papillary carcinoma). All of the lesions were compared with a set of cases in which ductal carcinoma in situ (DCIS) (n = 20) or invasive carcinoma (INV)(n = 13) was accompanied by MPs. The MP cases had a characteristic morphologic appearance, typically presenting as a mass comprising multiple adjacent ducts filled by papillomas, accompanied by dense fibrosis and intermingled with various proliferative fibrocystic lesions, particularly florid adenosis. Atypical hyperplasia was a frequent finding (in 12 of 28 cases; 43%), particularly in cases with atypical papillomas (7 of 11; 63.6%). Although contralateral lesions occurred in 4 of 28 patients (14.2%; 3 MPs and 1 INV), only 1 patient (4%) has developed ipsilateral breast carcinoma (mean follow-up, 47 months). DCIS associated with MP was typically low grade (17 of 20; 85%) and arose from areas within or immediately adjacent to preexisting benign lesions. None has recurred (mean follow-up, 41 months), although 1 patient has contralateral MP and 3 patients (23%) have developed carcinomas in the opposite breast. INVs developing in a background of (ipsilateral) MPs were mostly small (8 of 11 <2.0 cm), node negative (7 of 10), and estrogen receptor (ER) positive (8 of 8). Only 1 of 13 patients (8%) has died from disease (mean follow-up, 59 months), but 5 (38%) have developed contralateral breast lesions (including 1 MP, 1 MP-DCIS, 1 DCIS, 1 LCIS, and 1 INV). We conclude that the frequent associations with ADH, ALH/LCIS, malignant lesions, and bilaterality imply that MP may represent a marker of constitutionally increased breast cancer risk. Because carcinomas arose within or close to areas involved by preexisting benign MP lesions, it may also be appropriate to excise segments of tissue involved by MP, particularly cases with atypia, and closely monitor for contralateral disease.