Pathology and Somatic Alterations in Hereditary Lobular Breast Cancers

The most frequent special histological type of breast cancer is represented by invasive lobular carcinoma (ILC), which makes up about 15% of all invasive breast carcinomas. The molecular signature of ILC is the dysregulation of E-cadherin due to CDH1 abnormalities. Although CDH1 germline mutations are very uncommon in women with early-onset and/or familial ILC, they are the most common detrimental non-BRCA mutations and are thought to be the origin of a significant fraction of lobular breast cancer. Since the morphology and immunophenotype of hereditary and non-hereditary ILCs are nearly identical, no specific histopathological findings can be used to distinguish between the two. High-throughput sequencing studies revealed that ILCs represent a separate entity at the genomic level. This chapter addresses the very important topic of ILC morpho-molecular characteristics in the setting of germline and/or somatic CDH1 abnormalities.