Answer: In-situ and infiltrating lobular carcinoma

Histology: The tumor consists of an in situ component which is composed of somewhat pleomorphic tumor cells with central comedo-type necrosis with microcalcification. This creates an excellent mimic of ductal carcinoma in situ. However, closer inspection of the tumor cells reveals that they are dyscohesive and the nuclei are often eccentric, yielding a signet ring appearance. Also associated with this lesion is an invasive component consisting of cords of tumor cells infiltrating in a single file pattern. These cells, like the in situ component, have significant pleomorphism. Immunostain for E-cadherin was performed and was completely negative in the lesion, supporting the diagnosis of in situ and infiltrating lobular carcinoma, with pleomorphic features.

Discussion: The main differential diagnosis here is in situ and infiltrating ductal carcinoma. While the absence of E-cadherin immunostaining establishes the lesion as lobular, the single-file infiltrating growth pattern of the invasive component, as well as the dyscohesive nature of the tumor cells and their signet ring cell-like appearance in the in situ component, are histologic clues to the lobular nature of this lesion. The infiltrating component has a single-file pattern that is not rounded at its edges and does not fit an established type of adenosis. It irregularly infiltrates fat, which is another feature supporting invasion.

Classic invasive lobular carcinomas are characterized by distinctive architecture (single-file growth pattern, low cellular density) and cytology (uniform small cells, often with intercytoplasmic mucin). Variants of invasive lobular carcinoma include architectural variants, such as solid, alveolar, or tubululolobular, and cytologic variants, such as pleomorphic lobular carcinoma. Invasive lobular carcinomas are typically immunoreactive for estrogen and progesterone receptors, but are very infrequently Her-2/neu overexpressors. Occasional plromorphic lobular carcinomas will overexpress Her-2/neu. Regardless, invasive lobular carcinomas should be Elston graded, just as invasive ductal carcinomas are. The majority of the lesions will be Elston grade 2. The current lesion qualified as Elston grade 3/3, based on the high mitotic rate.