Ms. MM is a 78–year–old female former smoker with history of MAI, OSA, HTN, and anxiety admitted with hypercalcemia and FTT. Primary complaints were progressive weakness, malaise, weight loss, and decreased appetite. Exam was notable for dysarthric speech, dysmetria, and ataxic gait. Three months PTA, she had visited the ED due to progressive decline, and was worked up with NCHCT (unremarkable) and MR brain (deep white matter changes consistent with small vessel ischemic disease). At that time, neurology was consulted, and recommended PT eval and labs (UA, HgbA1c, TSH, FT4, folic acid, B12), all negative. At neurology follow–up, she was set up with EMG (normal), MR c–spine (degenerative changes), and paraneoplastic panel was drawn given ongoing symptoms. By the time of admission 1 month later, the panel was noted to be positive for Purkinje Cell Antibody type 1 (anti–Yo) with a titer of 1:245,760 (normal <1:240) consistent with paraneoplastic cerebellar degeneration (PCD). Given anti–Yo’s association with gynecologic malignancies, the patient had a pelvic US and CT abdomen/pelvis, which were unremarkable; mammogram was up to date. PET scan had intense uptake in the right axillary lymph nodes. Axillary lymph node biopsy revealed carcinoma with prominent lymphoid stroma. Immunostains were positive for CK7 and Her–2/neu, and negative for estrogen and progesterone receptors; biopsy report was revised to indicate breast cancer, either primary in tail of the breast, or metastatic. MR demonstrated two pathologic axillary lymph nodes, but no evidence for breast cancer. Lymph node dissection indicated 2 of 14 nodes positive. Ms. MM was given pulse solumedrol and IVIG X 5 days. As an outpatient, she received a dose of cyclophosphamide for further immunosuppression and chemotherapy for metastatic breast cancer with weekly Taxol/Herceptin. She had progressive decline, was enrolled in hospice, and expired 3 months after initial admission.
Paraneoplastic cerebellar degeneration is due to anti–Yo antibodies which exist in cases of breast and ovarian cancer, and more rarely uterine, bronchial, and gastric cancer. The antibody against the tumor also acts against cerebellar cells leading to ataxia and tremors, with degeneration on imaging. In a majority of cases, the cancer has already metastasized by time of diagnosis. Patients have rapid decline and most are bedbound within 3 months. Attempts to treat the condition with chemotherapy or immunosuppression usually do not lead to significant improvement in neurologic symptoms.
Paraneoplastic cerebellar degeneration should be considered in elderly patients with progressive cerebellar symptoms. Diagnosis is confirmed by elevated anti–Yo levels on paraneoplastic panel, and should prompt a search for underlying malignancy, often breast or ovarian.