To describe a unique case of AQP4-IgG–positive NMOSD in a patient with two simultaneous malignancies—metastatic rectal adenocarcinoma and a lung carcinoid tumor—and to contextualize the presentation within the existing paraneoplastic NMOSD literature.

Neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin-4 immunoglobulin G (AQP4-IgG) can rarely occur in a paraneoplastic context. Tumor expression of AQP4 has been demonstrated in select malignancies, including carcinoid tumors, suggesting a potential antigenic trigger. Recognition of such cases is critical, particularly in older adults or patients with concurrent neoplasia.

We reviewed the patient’s clinical, radiologic, and laboratory data, including cerebrospinal fluid (CSF) analysis and MRI findings, and compared them with published reports of paraneoplastic NMOSD.

A 69-year-old woman with rectal adenocarcinoma (with liver metastases) and a lung carcinoid tumor presented with progressive weakness, sensory loss, and sphincter dysfunction. MRI demonstrated longitudinally extensive T2 hyperintense lesions from C2–C6 and T3–T8 with additional periependymal and temporal FLAIR changes. CSF showed lymphocytic pleocytosis and positive oligoclonal bands. Serum AQP4-IgG was strongly positive by cell-based assay, confirming NMOSD. The patient improved markedly with high-dose corticosteroids and plasma exchange and was discharged on maintenance rituximab. Given the advanced age and concurrent malignancies, a paraneoplastic mechanism was suspected; however, tumor AQP4 expression could not be confirmed.

This case expands the spectrum of reported paraneoplastic NMOSD and underscores the importance of cancer screening in older patients with new-onset AQP4-IgG–positive disease. While the coexistence of adenocarcinoma and carcinoid tumors suggests a possible paraneoplastic trigger, definitive causality requires demonstration of tumor AQP4 expression. The presence of CSF oligoclonal bands, though atypical for NMOSD, does not exclude the diagnosis when supported by AQP4 seropositivity and characteristic imaging. Awareness of potential paraneoplastic associations can guide early malignancy evaluation and prompt immunotherapy initiation.