Unveiling the Uncommon: Paraneoplastic Cerebellar Degeneration, a Rare Presentation of HER2-Positive Breast Cancer

Paraneoplastic syndromes (PNS) are triggered by an altered immune system response to a neoplasm. The symptoms of PNS usually precede malignancy making its diagnosis difficult. They are rarely associated with breast cancer. We report a case of a 25-year-old woman who presented with subacute cerebellar degeneration with no positive findings on MRI brain or routine cerebrospinal fluid (CSF) cytology. She did not improve with steroids or plasmapheresis. She was incidentally detected with a right-sided breast lump on FDG-PET CECT. An ultrasound of the breast showed a well-defined hypoechoic lesion of 2 × 1.5 × 1.2 cm in right breast graded as Breast Imaging Reporting and Data System (BIRADS-4a). A diagnostic excision biopsy of the breast lump showed human epidermal growth factor receptor 2 (HER2)/neu positive invasive ductal carcinoma of the breast. She had no distant metastases and had positive anti-Yo/Purkinje cell cytoplasmic antibody type 1 antibody in CSF. A diagnosis of PNS along with a cT1N0M0 breast cancer, was thus confirmed. She showed immediate symptomatic relief after excision biopsy which further improved with chemotherapy and anti-HER2-based targeted therapy. A high index of clinical suspicion, a multitude of imaging modalities, and other relevant investigations in a patient presenting with neurological symptoms are needed to accurately and promptly diagnose the malignancy. PNS in breast cancer is peculiarly associated with HER2-positive tumors due a cross-reaction between sensitized T cells and cerebellar degeneration–-related protein 2 proteins, which are expressed by Purkinje cells in the brain and in HER2 positive tumors. Prompt treatment of the malignancy improves neurological recovery.