Intraductal papillomas are benign lesions that can be divided into two groups: central papillomas, which involve large ducts and are usually solitary, and peripheral papillomas, which involve the terminal duct lobular units and are usually multiple (Fig. 8.1).

Central papillomas are tumors of the major lactiferous ducts and are most frequently observed in women 30 to 50 years of age. Patients usually present with nipple discharge that may be bloody; on occasion, the lesion reaches sufficient size to produce a palpable, subareolar mass. Peripheral papillomas occur in somewhat younger patients and less often present with nipple discharge or a mass.1 They may occasionally present as a mammographic abnormality (microcalcifications or multiple densities).

Central papillomas are generally <1 cm in diameter, but occasionally may be as large as 4 or 5 cm. On gross examination, they appear as tanpink, circumscribed nodules within a dilated duct or cyst. A frankly papillary configuration may be apparent, but more typically the lesion has a bosselated surface. The tumor may be attached to the wall of the involved duct by a stalk or may be sessile. Peripheral papillomas are usually not identifiable on gross examination.

On histologic examination, papillomas are composed of arborizing fronds with well-developed fibrovascular cores (Fig. 8.1, e-Fig. 8.1). The papillary fronds are covered by an inner myoepithelial cell layer and an outer epithelial layer (Fig. 8.2, e-Fig. 8.2). The myoepithelial layer is variably prominent, but is always present. In problematic cases, myoepithelial cells can be highlighted by immunostaining for actin, smooth muscle myosin heavy chain, calponin, p63, or other myoepithelial cell markers (Fig. 8.3, e-Fig. 8.3). Myoepithelial cells are also present at the periphery of the involved duct(s) (Fig. 8.4, e-Fig. 8.3) (Table 8.1). The epithelium of benign papillomas may consist of one or a few layers of cuboidal to columnar cells or it may show varying degrees of usual ductal hyperplasia (UDH). The epithelial hyperplasia may be extreme and may grow in a contiguous fashion between adjacent papillae (Fig. 8.5, e-Fig. 8.4). In some cases, the epithelial proliferation may in areas have the appearance of atypical ductal hyperplasia (ADH) or DCIS (see subsequent text). Apocrine metaplasia is frequent (Fig. 8.6, e-Fig. 8.5); squamous metaplasia may also be seen.2 Varying degrees of myoepithelial hyperplasia may be observed in some cases (Fig. 8.7). The hyperplastic myoepithelial cells can be epithelioid or spindle-shaped and may have abundant clear cytoplasm. The myoepithelial cell component may be sufficiently prominent that the foci resemble areas of adenomyoepithelioma (e-Fig. 8.6) (see subsequent text). Collagenous spherulosis is yet another change that may be seen in the epithelium of intraductal papillomas; this should not be misinterpreted as an area of ADH or DCIS (Fig. 8.8, e-Fig. 8.7) (see subsequent text).

The papillary fronds and/or the surrounding duct wall may show varying degrees of stromal fibrosis and may contain entrapped glands and/or solid epithelial cell nests. On occasion, the fibrosis is so extensive that it distorts or obscures the underlying papillary architecture. In such cases, the term sclerosing papilloma is appropriate. In the most extreme cases, the features overlap with those of a ductal adenoma (see subsequent text) or complex sclerosing lesion. The presence of glands or epithelial nests within a fibrous stroma may produce a worrisome appearance that raises the question of an invasive carcinoma (Fig. 8.9, e-Fig. 8.8). However, in benign intraductal papillomas with sclerosis, myoepithelial cells are discernible around at least some of the entrapped glands and epithelial nests, which is a feature supporting the benign nature of this process. In addition, the stroma of these lesions typically has a more hyalinized, sclerotic appearance than the stroma associated with invasive carcinomas.

Benign papillomas may undergo infarction, particularly larger central lesions; this may occur spontaneously or may be associated with trauma, such as a needling procedure (fine-needle aspiration or core-needle biopsy). Infarction is frequently associated with entrapment of benign epithelium at the periphery of the lesion. The entrapped epithelium may exhibit reactive cytologic atypia or squamous metaplasia (Fig. 8.10, e-Fig. 8.9).3

Although the histologic features of peripheral papillomas are similar to those of central papillomas, the epithelium of the peripheral lesions more often shows foci of ADH and DCIS than that of solitary, central papillomas.4,5

Intraductal papillomas are benign lesions that are adequately treated by excision. The risk of subsequent breast cancer associated with solitary intraductal papillomas is similar to that of women with other proliferative lesions without atypia (relative risk ∽2 compared with the general population). Multiple papillomas appear to be associated with a higher risk of concurrent and subsequent carcinoma than do solitary, central papillomas.1,5, 6 and 7 The key features of intraductal papillomas are summarized in Table 8.2.