Paraneoplastic Neuromyelitis Optica Spectrum Disorder: A single center cohort description with two cases of histological validation

Background Paraneoplastic syndromes are remote effects of cancer caused by an autoimmune response triggered by tumor cells. Paraneoplastic Neuromyelitis Optica Spectrum Disorders (NMOSD) has been previously described, but the underlying mechanism for these rare cases is not well characterized. This paper presents a newly described case series of paraneoplastic NMOSD, including 2 new histological types of cancer and histological validation. Methods The UBC NMO clinic database was surveyed and identified 6 patients with paraneoplastic NMOSD. In 2 cases, aquaporin-4 (AQP4) immunoreactivity was assessed on patients’ tumor specimens. Results The mean age at NMOSD diagnosis was 56 years old and 5/6 patients were older than 50 years old. 4/6 patients with paraneoplastic NMOSD have positive AQP4 antibodies. The median time between NMOSD and cancer was 12 months. Two new cancer types- serous ovarian carcinoma and adrenocortical carcinoma - were found in paraneoplastic NMOSD cases. A serous ovarian carcinoma and a thymoma, found in patients with AQP4 serological evidence, showed a positive reactivity to AQP4 immunostaining. Conclusions Our findings will increase the recognition of NMOSD as a paraneoplastic syndrome. Cancer cells can express AQP4, increasing the likelihood of a direct mechanism between cancer cells and the development of NMOSD in paraneoplastic cases.