Multiple ANNA-2 paraneoplastic syndromes have been identified in association with breast cancer. But a PSP phenotype has been rarely reported, with extremely scant literature of any ANNA-2 association with such presentation.

A 55 year old Caucasian female with history of stage IIB invasive ductal carcinoma of the breast status post bilateral mastectomy and 6 cycles of FEC/Tax chemotherapy 3 years prior to presentation. The patient was in remission for 2 years until she presented with bilateral lower extremity weakness and frequent backward falls, hand tremor, vertical/oblique diplopia, and dysphagia of 3 months duration. She had an unremarkable brain MRI prior to admission. Presenting exam revealed normal cognition, “astonished-like” facial expression, retrocollis, restricted upward and lateral gaze bilaterally, preferred downward gaze, absent convergence, intact vestibulo-ocular reflex, intermittent resting hand tremor, and 4+/5 power throughout consistent with PSP. However, rapid progression was atypical and paraneoplastic syndrome was considered. High dose IV methylprednisolone was started empirically with minimal improvement.  PET-CT revealed bilateral hilar lymphadenopathy, lung and pleural heterogenous nodularities, and a T10 vertebral focus. An endobronchial lymph node biopsy was performed and plasma exchange was started with noted improvement in lateral and vertical gaze by third session. Biopsy revealed metastatic adenocarcinoma of the breast and oncology began treatment. Serum paraneoplastic panel revealed ANNA-2 with titer of 1:30720. She received rituximab infusion once prior to discharge, with discharge planning for continued chemotherapy and maintenance rituximab.

PSP phenotype has been very rarely reported as a paraneoplastic syndrome associated with classic neuronal antibodies and malignancies.  Our patient presented with corticosteroid and PLEX responsive ANNA-2 positive paraneoplastic PSP phenotype associated with breast cancer.