Abnormal neurons in teratomas in NMDAR encephalitis.

IMPORTANCE: Ovarian teratomas are frequently described in patients with N-methyl-d-aspartate receptor (NMDAR) encephalitis, yet NMDAR encephalitis is rarely described in patients with ovarian teratomas. Understanding why a minority of patients with teratomas are seen with autoimmune encephalitis may improve the management of NMDAR encephalitis and other teratoma-associated autoimmune diseases.

OBJECTIVE: To characterize the unique organization of neuroglial elements within ovarian teratomas resected from patients with NMDAR encephalitis.

DESIGN: Case-control study comparing the pathological features of ovarian teratomas resected from consecutively accrued cases with NMDAR encephalitis between January 1, 2009, and December 15, 2013, and ovarian teratomas resected from controls between June 1, 2012, and June 30, 2013.

SETTING: Pathology tissue database at a tertiary academic care center.

PARTICIPANTS: Five cases with teratoma-associated NMDAR encephalitis and serum or cerebrospinal fluid autoantibodies against central nervous system (CNS) NMDAR and 38 controls (39 ovarian teratomas) without neurological symptoms or signs.

EXPOSURES: Formalin-fixed, paraffin-embedded ovarian teratomas were examined for the presence of CNS tissue and inflammatory infiltrates using direct microscopy, enhanced with standard histopathological and immunological stains.

MAIN OUTCOMES AND MEASURES: Frequency of detection of atypical (dysplastic) CNS neuronal elements in ovarian teratomas resected from cases vs controls, as well as characterization of the relationship between atypical neurons and immune infiltrates.

RESULTS: Central nervous system neuronal elements were detected in 4 of 5 teratomas resected from cases with NMDAR encephalitis and in 20 of 39 controls (P = .36). Atypical neurons were seen within teratomas resected from 4 of 5 cases but not in 39 controls, reliably distinguishing teratomas associated with NMDAR encephalitis (P < .001). If found within the CNS, these histological abnormalities would have received the diagnosis of gangliogliomas (n = 3) and ganglioneuroblastoma (n = 1). Reactive changes were present in teratomas from controls, including ferruginated neurons and Rosenthal fibers. Abnormal neuroglial elements were closely related to immune infiltrates in teratomas resected from 4 of 4 cases. Inflammatory infiltrates were not associated with neuroglial tissue in 20 controls, further differentiating these populations (P < .001).

CONCLUSIONS AND RELEVANCE: Abnormal neurons within teratomas distinguish cases with NMDAR encephalitis from controls and may promote the development of autoimmunity.