Papillary lesions of the breast constitute around 5% of breast lesions. They may be benign, atypical or malignant, and can be classified into the following categories (Collins and Schnitt, 2008):
- benign intraductal papilloma,
- benign intraductal papilloma with usual type hyperplasia,
- intraductal papilloma with focal atypia,
- intraductal papilloma with focal ductal carcinoma in situ (DCIS),
- intracystic papillary carcinoma,
- solid encapsulated papillary carcinoma.
Benign and atypical lesions are more common in women in their 40’s and usually present with nipple discharge. Malignant lesions develop in older women and may present as a mass or a mammographic abnormality. Tissue diagnosis can be carried out by cytological examination of the nipple discharge or by fine-needle aspiration or core biopsy if a mass lesion is identified either clinically or radiologically. In the UK, where core biopsies are in wide use, papillary lesions, benign or atypical, are usually given a minimum of B3 score and excision is carried out either by surgery or by the use of vacuum core biopsy. This is to allow microscopic examination of the entire lesion and exclude the presence of atypia or malignancy. If there are definite malignant features in the core (see below), a score of B5 is given and surgical excision is carried out.
Benign and atypical intraductal papillomas
These are discrete intraductal polypoid lesions with arborizing fibrovascular stroma covered by two layers of cells: a myoepithelial layer and a columnar or a cuboidal luminal epithelial layer (Collins and Schnitt, 2008; Fig. 1). They are usually divided into central and peripheral. Central papillomas are usually subareolar and are mostly single, but can reach considerable sizes and become symptomatic. Peripheral papillomas are generally smaller, but may be multiple and recurrent. A patient is usually considered to have multiple papillomas if she has five or more lesions.
Excessive epithelial proliferation, that is, hyperplasia may be present. The latter is defined as the presence of more than four layers of epithelial cells covering the papillary fronds and can be of the usual (Fig. 2) or the atypical type (Page et al., 1996). In regular hyperplasia, the cells are not uniform and slit-like spaces may be present. In atypical hyperplasia, cell uniformity and regularly rounded spaces are present, but the affected area is less than 3 mm across (Page et al., 1996). If the atypical cells occupy more than 3 mm, the lesion is considered DCIS (Page et al., 1996). Atypical hyperplasia may be present within or adjacent to the papilloma.
In a review of 9108 benign breast cases, papillomas were found in 480 (5%). Most of these (372; 78%) were single with no atypia, whereas 54 (11%) were single with atypia, 41 (8%) were multiple without atypia and 13 (2%) were multiple with atypia (Lewis et al., 2006). The relative risk of breast cancer development in this large series was two for patients with single papillomas and no atypia (similar to proliferative breast disease without atypia), three for patients with multiple papillomas and no atypia, five for patients with single papillomas with atypia and seven for patients with multiple papillomas with atypia (Lewis et al., 2006). In another study, the presence of cellular atypia within, or outside, the papilloma was rather than is associated with a four-fold increased risk of carcinoma (Raju and Vertes, 1996). When the latter develops, it usually arises in the same breast and possibly closer to the site of the previously excised papilloma (Raju and Vertes, 1996; Lewis et al., 2006).
Papillomas may show wide areas of sclerosis and microcalcification, particularly in postmenopausal women. Apocrine metaplasia is common and usually indicates that the lesion is benign. Infarction and squamous metaplasia may also occur (Flint and Oberman, 1984). Necrosis is not a feature, but an occasional mitotic figure may be present.
Intracystic and solid papillary carcinoma
These are well-defined lesions composed of neoplastic epithelial cells that are larger than those present in benign lesions and have larger monotonous nuclei with no intervening myoepithelial cells. This can be observed by staining the section for cytokeratin 5 (CK5), where all the cells will be negative. This is in contrast to benign lesions, where CK5-positive myoepithelial cells will be observed underneath the CK5-negative luminal epithelial cells (Fig. 1). If the papillary pattern is still recognizable, in the form of fronds covered by the neoplastic cells, the lesion is called intracystic papillary carcinoma (Fig. 3). If the papillary fronds can no longer be recognized, but are only represented by small islands within the lesion containing fibrous tissue and blood vessels, the lesion is called a solid papillary carcinoma (Fig. 4). Both lesions are usually surrounded by condensed fibrous tissue; hence, they are also called encapsulated papillary carcinomas. In the solid variety, a cribriform pattern of proliferation is sometimes seen. The lesions may be associated with adjacent foci of DCIS or invasive carcinoma. Most encapsulated papillary carcinomas are ER-positive, but ER-negative cases are sometimes encountered (personal observation). Myoepithelial cells may or may not be present around the lesions.
There is currently a debate about whether these encysted lesions are truly in situ or low-grade invasive cancers with a pushing, rather than an infiltrative, margin. This is because many of these lesions have not been found to be surrounded by myoepithelial cells (Hull and Yeh, 2005; Collins et al., 2006; Mulligan and O'Malley, 2007; Collins and Schnitt, 2008; Esposito et al., 2009) and occasional cases with lymph node metastasis have been reported (Mulligan and O'Malley, 2007). However, the basement membrane material is usually found around these lesions as observed by moderate to intense staining for collagen type-IV (Esposito et al., 2009). The issue remains unsettled and the recommendation given by Collins and Schnitt (2008) is to add a note to the histology report stating that ‘although some recent studies have suggested that encapsulated papillary carcinoma may represent circumscribed nodules of low-grade invasive carcinoma rather than in-situ lesions, they should be managed in a manner similar to DCIS’. If there is an associated invasive carcinoma, only the size of the invasive component is taken into consideration in deciding the stage of the disease (Collins and Schnitt, 2008).
Differentiating benign from malignant papillary lesions in core biopsies
The majority of papillary lesions are benign and the core biopsy will show obvious fibrous tissue fronds covered by two layers of epithelial and myoepithelial cells (Fig. 5). The ratio of epithelial to fibrous tissue is important, and it is only when there is an abundant epithelial proliferation that immunohistochemistry may be required. Staining for CK5 will be completely negative, within the proliferating cells and in malignant lesions, whereas the benign ones will show a mosaic of positive and negative cells.
Conflicts of interest
There are no conflicts of interest.
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