Papillary lesions of the breast – review and practical issues

Papillary lesions of the breast encompass a broad spectrum of diseases ranging from benign and atypical lesions to malignant ones. They represent a heterogeneous group of neoplasm featuring fibrovascular cores covered by epithelial cells with or without intervening myoepithelial cells.  According to the World Health Organization classification of breast tumors,1 papillary lesions of the breast are further classified into intraductal papilloma (including intraductal papilloma with atypical ductal hyperplasia (ADH)/ductal carcinoma in situ (DCIS)), papillary DCIS, encapsulated papillary carcinoma, solid papillary carcinoma (in situ and invasive) and invasive papillary carcinoma. The clinical manifestation of this group of disease varies. They can present with nipple discharge when centrally located, or as palpable masses when located near the surface or are relatively large. Deeper lesion can be revealed by ultrasound, mammography and magnetic resonance imaging. Smaller lesions can also be picked up incidentally in breast biopsy or excision obtained for other reasons. The overlapping morphological features and immunohistochemical (IHC) profiles make accurate diagnosis of breast papillary lesion a challenge for pathologists, especially in the setting of core needle biopsy (CNB), in which the tissue for assessment is a minute fraction of the lesion, and may not demonstrate the telltale architecture. In the external quality assurance scheme of the UK National Health Service Breast Screening, papillary lesions belong to the most frequently misinterpreted breast lesions, particularly basing on HE sections alone.2 The diagnostic difficulty is also reflected by the increasing publications covering the diagnostic challenge of breast papillary lesions2, 3, 4, 5, 6, 7, 8, 9, 10, 11

The pathogenesis of papillary lesions is still enigmatic. Although increasing numbers of genetic studies are trying to characterize their pathogenesis, the solid and distinct molecular features which are diagnostically useful are still lacking.

In this review, the morphological and relevant IHC features of breast papillary lesions will be discussed, with further emphasis on some commonly-encountered practical diagnostic issues. A simple diagnostic algorithm will be established. The relevant molecular characteristics will be discussed as well. Invasive micropapillary carcinoma, which lacks true papillae, and tall cell carcinoma with reversed polarity, a recently-recognized separate entity included in the 5th edition of the WHO classification, will also be included, because of the potential confusing terminology and similar solid papillary growth pattern, respectively.

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