Fulminant Paraneoplastic Neuromyelitis Optica Spectrum Disorder (NMOSD) with Triple-negative, Aquaporin-4-positive Breast Cancer
Hemali Patel1, Fernando Cuascut Lassus1, Ibrahim Noorbhai1, Joseph Kass1
1Baylor College of Medicine
Objective:
We aim to discuss the clinical presentation of a paraneoplastic neuromyelitis optica spectrum disorder (NMOSD) associated with pathology confirmed AQP4+ and triple-negative breast cancer and identify clinical patterns that could suggest an underlying malignancy.
Background:
An estimated 80% of NMOSD cases have IgG antibodies to the AQP4 channel. It has been reported that up to 5% of AQP4-seropositive cases can be paraneoplastic. Like other paraneoplastic conditions, it is attributed to an immune-mediated response to tumor-cell expression of AQP4. Previously available literature suggested that out of 11 tumors tested, AQP4 expression was present in 63.6% of cases. The current paraneoplastic incidence of seropositive NMOSD is thought to be so low that it often does not arise on the clinical differential. The ability to perform immunostaining on tissue for AQP4 expression is also limited at this time.
Design/Methods:
We describe the case with images, and review the literature.
Results:
This is a case of a young female who presented with an initially nonfocal and vague examination with fulminant worsening whilst inpatient including tetraplegia, neurogenic bladder and progressive mental status changes. Serum AQP4 IgG titer was high confirming NMOSD diagnosis. After acute respiratory decompensation necessitating intubation, a CT chest revealed lymphadenopathy with concern for breast tumor. Her neurological function continued to deteriorate with follow up MRI revealing extensive CNS demyelination not visualized ~1 week prior. Repeat CT showed worsening lymphadenopathy, tissue biopsy confirmed triple-negative stage IV breast cancer. The resected tumor was sent for immunostaining and the neoplastic cells stained positive for AQP4 expression.
Conclusions:
This case along with the available literature suggests the need to consider paraneoplastic causes in especially aggressive NMOSD. Increasing immunostaining capabilities combined with increasing clinician suspicion for paraneoplastic causes will lead to a better understanding of the true incidence of paraneoplastic NMOSD as well as improved diagnosis and treatment of these patients.