NMOSD is one of demyelinating, autoimmune disease affecting the central nervous system. In most cases, NMOSD is associated with autoantibodies targeting AQP-4. Herein, we reported a rare case of a 60-year-old woman with paraneoplastic NMOSD associated with breast cancer.
Autoimmune diseases are sometimes associated with neoplasms. Patients with NMOSD occasionally develop carcinomas. Several case reports have demonstrated AQP-4 expression in tumor tissue, and the prevalence of cancer in patients with NMOSD associated with positive AQP4-IgG antibodies has been reported incidentally in 0.02% . There are quite rare cases presenting as a paraneoplastic syndrome in association with carcinomas , such as carcinoma of lung [5, 6], esophageal , small-bowel neuroendocrine tumor , carcinoid tumor of the stomach , thymoma, breast carcinoma, lymphoma. As a result, the possibility of underlying malignancy should be considered in patients with the diagnosis of NMOSD, especially in the elderly. What triggers the production of AQP4-IgG antibodies in patients with malignancy has been poorly understood, but it has been speculated that such antibody production is triggered by an immune response against a patient’s cancer.  However, AQP-4 is also expressed in neurologically normal patients’ tumors, suggesting additional factors are required for NMOSD induction in patients with cancer . AQP4-IgG may involve in the pathogenesis of paraneoplastic NMOSD, however, its clinical utility and underlying exact mechanism warrant further investigations.
Breast cancer has been proved to be related paraneoplastic endocrine syndromes with neurologic syndromes. As for the breast carcinoma found in NMOSD, there was an observation about 41 patients with positive NMO-IgG, six malignancies were identified in five NMOSD seropositive patients, inluding breast carcinoma (three cases), lymphoma, cervical carcinoma and leiomyosarcoma (in a patient who also had breast carcinoma) . Furthermore, from another studies of 34 paraneoplastic NMOSD cases, 11 (32%) cases had breast carcinoma . We should attach importance to the detection of paraneoplastic etiology, especially the breast carcinoma in NMOSD cases.
The strengths of our case were showed as follows. Firstly, we reported a rare case of a 60-year-old woman with paraneoplastic NMOSD associated with breast cancer. The final of diagnosis of paraneoplastic NMOSD was performed, which was based on the patient’s progressing neurological symptoms, MRI findings both in brain and spine, and breast cancer, the positive AQP-4 autoantibodies, and the effect of treatment. Secondly, our case was finally diagnosed as paraneoplastic NMOSD after the occurrence of breast cancer with the interval of 3 years. As a result, clinical findings suggestive of NMOSD in elderly patients should raise the suspicion of paraneoplastic etiology and warrants thorough investigations for an underlying cancer, with long-term follow-ups, at least for several years. Thirdly, this case was combined with the diagnosis of pulmonary embolism and venous thrombosis in both lower limbs and right peroneal vein, which may be due to the hypercoagulable state from the breast cancer, which could also support the paraneoplastic syndrome may also occur in NMOSD cases.