Invasive lobular breast carcinoma metastasising to the rectum.

Gastrointestinal (GI) metastasis from a primary breast carcinoma is uncommon, with the rectum being one of the least reported sites in the literature. We report a case of a 79-year-old woman who underwent treatment for an infiltrative lobular carcinoma of the right breast with nodal involvement, and 10 years later developed recurrence in the form of rectal metastasis. Spread to the GI tract is most commonly seen with lobular breast carcinomas. Any patient with a history of breast cancer presenting typically or atypically with abdominal symptoms or altered bowel habit should raise a high index of suspicion for recurrent or metastatic disease.

ß-III spectrin underpins ankyrin R function in Purkinje cell dendritic trees: protein complex critical for sodium channel activity is impaired by SCA5-associated mutations.

Beta III spectrin is present throughout the elaborate dendritic tree of cerebellar Purkinje cells and is required for normal neuronal morphology and cell survival. Spinocerebellar ataxia type 5 (SCA5) and spectrin associated autosomal recessive cerebellar ataxia type 1 are human neurodegenerative diseases involving progressive gait ataxia and cerebellar atrophy. Both disorders appear to result from loss of ß-III spectrin function. Further elucidation of ß-III spectrin function is therefore needed to understand disease mechanisms and identify potential therapeutic options. Here, we report that ß-III spectrin is essential for the recruitment and maintenance of ankyrin R at the plasma membrane of Purkinje cell dendrites. Two SCA5-associated mutations of ß-III spectrin both reduce ankyrin R levels at the cell membrane. Moreover, a wild-type ß-III spectrin/ankyrin-R complex increases sodium channel levels and activity in cell culture, whereas mutant ß-III spectrin complexes fail to enhance sodium currents. This suggests impaired ability to form stable complexes between the adaptor protein ankyrin R and its interacting partners in the Purkinje cell dendritic tree is a key mechanism by which mutant forms of ß-III spectrin cause ataxia, initially by Purkinje cell dysfunction and exacerbated by subsequent cell death.