Aquaporin-4 IgG Positive Neuromyelitis Optica Spectrum Disorder: Frequency and Type of Cancer Co-Existence, Antigen Expression and Proof of Paraneoplastic Phenotype
Naga Pradyumna Kothapalli1, Yong Guo1, Dean Wingerchuk1, Eoin Flanagan1, Divyanshu Dubey1, Fernando Cuascut Lassus2, Hemali Patel2, Nanthaya Tisavipat1, Mark Keegan1, W. Tobin1, Cristina Valencia Sanchez3, Claudia Lucchinetti4, Sean Pittock5
1Mayo Clinic, 2Baylor College of Medicine, 3Mayo Clinic Arizona, 4University of Texas/Dell Medical School, Health Learning Blg, 5Mayo Clinic Dept of Neurology
Objective:
To report malignancy screening data in a large AQP4+NMOSD cohort and investigate the AQP4 expression in tumor tissues.
Background:
The link between tumors expressing AQP4 and NMOSD onset is a fascinating area of research. Paraneoplastic AQP4+NMOSD (PAN) was labeled by prior studies to have a male predominance, area postrema syndrome at onset, definite association of adenocarcinomas, without emphasis on demonstrating AQP4 expression on tumors.
Design/Methods:
Retrospective chart analysis was performed in AQP4+NMOSD cohort; patients with cancers diagnosis independent of the time cutoff from the onset of NMOSD were identified; tumor tissues underwent immunohistochemical (IHC) analysis for AQP4 expression, cases tested positive were classified as PAN. Age-appropriate (AA) malignancy screening data was gathered per American Cancer Society guidelines.
Results:
33 NMO patients had coexisting malignancies (male=6, female=27) with median age of onset (MAO) of 57 years (range 15-71), comprising 9% of AQP4-NMOSD cohort.

 

 AQP4 expression was present in 4/13 tumors tested. All 4 were women (MOA 57, range 30-59 years), cancers were identified 29 months (range 1-86) after NMOSD onset. Patient 1, with recurrent ON, had serous ovarian adenocarcinoma; Patient 2, with recurrent LETM, had papillary thyroid carcinoma; Patient 3, with area postrema attack, had ductal carcinoma breast. Patient 4, with multifocal attack had poorly differentiated breast carcinoma.

AQP4 expression was absent- endometrial adenocarcinomas (2), lung squamous cell carcinoma (1), clear cell renal carcinomas (2), Lymphomas (4).  

In AQP4+NMOSD cohort (n=394, male=63, female=331), 40% (160, male=36, female=124) were in age of NMOSD onset >50 years subset. Complete AA malignancy screening was pursued in 19% of males, 19% of females; partial AA malignancy screening in 39% of males, 49% of females.

Conclusions:
Most of the coexisting malignancies are incidental per IHC analysis. PAN has no specific phenotypic preponderance or a definite association with adenocarcinomas. Further proteomic analysis studies are necessary to guide malignancy screening in AQP4+NMOSD.
10.1212/WNL.0000000000209063
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