Chapter 72: Lobular Carcinoma in Situ and Lobular Neoplasia

BACKGROUND

The term lobular neoplasia (LN) encompasses the entire spectrum of atypical epithelial lesions that originate in the terminal duct-lobular unit (TDLU) of the breast, and are characterized by a population of dyshesive cells, which expand the lobules and acini of the TDLUs, and may involve the terminal ducts in a pattern known as Pagetoid spread.¹ These lesions were traditionally described under the terms lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH), which refer to the degree of involvement of the acinar structures of a given TDLU.

The first description of LCIS, as an “atypical proliferation of acinar cells” of the breast, was reported by Ewing in 1919.² The main characteristics of this lesion, however, were not thoroughly documented until 1941 in the seminal study by Foote and Stewart.³ The term LCIS was chosen to emphasize the histologic similarities between the cells of LCIS and those of frankly invasive lobular carcinoma (ILC), and, importantly, was not meant to infer that the cell of origin resided in the lobules. In fact, it was acknowledged that LCIS would originate in the TDLU and small ducts. Based on the frequent identification of LCIS in association with ILC, and following the analogy of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), Foote and Stewart³ hypothesized that the neoplastic cells of LCIS would still be contained within a basement membrane, and that this lesion would constitute a precursor of breast cancer development, leading to the recommendation for mastectomy.

Emerging data throughout the 1970s from Haagensen et al⁴ and others⁵ demonstrated that the risk of breast cancer development following a diagnosis of LCIS was lower than that expected for a direct precursor lesion (approximately 1% per year) and was conferred equally to both breasts, generating controversy regarding the significance of LCIS and leading to disparate recommendations for management, ranging from observation only to bilateral mastectomy.

The term ALH was coined in 1978 to refer to a less prominent in situ proliferation composed of cells cytologically identical to those of LCIS which were associated with a significantly lower risk of subsequent breast cancer development; approximately one-half of the risk associated with LCIS.⁶ However, as the distinction between LCIS and ALH, which is based on quantitative rather than qualitative differences between the lesions (described below), often proves challenging in diagnostic specimens, Haagensen et al⁴ put forward the term “lobular neoplasia” to refer to the entire spectrum of these in situ lesions, including ALH and LCIS.

In addition to the classic forms of LN, several variants of LN have also been described. Of potential clinical significance is the pleomorphic variant (see below), first described in its pure form by Sneige et al⁷ under the name of pleomorphic lobular carcinoma in situ (PLCIS). Recognition of this variant is important, given that its histological features can lead to ...