Lobular carcinoma, not only a classic

Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia are rare lesions, found incidentally in breast biopsies. They have been regarded traditionally as high-risk lesions, but recent genetic evidence and follow-up data indicates that they also constitute nonobligate precursors of invasive carcinoma. In addition to 16q deletion, a genetic alteration common across the spectrum of low-grade mammary epithelial neoplasia, lobular lesions consistently demonstrate deletion or functional inactivation of the CDH1/E-cadherin gene, with consequent loss of membranous immunoreactivity for the same antigen. The use of E-cadherin in the evaluation of solid mammary carcinoma in situ with ambiguous morphology has identified variants of LCIS characterized by massive acinar expansion and necrosis with calcifications, and/or marked nuclear pleomorphism or signet ring cell formation. In contrast to classic LCIS, these rare lesions are detected mammographically and often occur in association with invasive carcinoma. Genetic analysis of these tumors has confirmed lobular lineage and demonstrated more extensive chromosomal alterations than in classic LCIS. A pleomorphic variant of invasive lobular carcinoma has also been described. Here, we summarize our evolving knowledge of in situ and invasive lobular neoplasia and highlight the implications for patient management.