Abstract
Encephalitis with anti-NMDAR antibodies (NMDAR-E) is a severe autoimmune neurological disorder, defined by a clinical presentation of encephalitis and the presence of IgG targeting the GluN1 subunit of NMDA receptors in the CSF. An underlying ovarian teratoma is commonly associated with this autoimmune disease suggesting a role of the tumor in immunopathogenesis. In this study, we characterized the salient histopathological features of 27 ovarian teratomas associated with NMDAR-E (3 immature and 24 mature teratomas) and 40 controls without associated encephalitis. All but one NMDAR-E-associated teratomas contained a nervous tissue component, while less than 40% of control teratomas did (p < 0.001). GluN1 expression by teratomatous nervous tissue seemed to be more often glial in NMDAR-E teratomas than in control teratomas (73% vs. 29%, p < 0.05). Strikingly, 3 out of 24 NMDAR-E-associated mature teratomas contained neuroglial tissue exhibiting histopathological features of central nervous system neuroglial tumor, while such glioma-like features are exceptionally described in the literature on ovarian teratomas. Moreover, NMDAR-E associated teratomas differed from sporadic ovarian teratomas by consistent and prominent infiltration of the nervous tissue component by immune cells, comprised of T- and B-cells and mature dendritic cells organized in tertiary lymphoid structures, with IgG and IgA deposits and plasma cells in close contact to the neuroglial tissue.These data demonstrate an association between massive infiltration of NMDAR-E-associated teratomas by immune cells and particular glial features of its neuroglial component, suggesting that this glial tissue might be involved in triggering or sustaining the anti-tumor response associated with the auto-immune neurological disease.
Highlights
Encephalitis (E) with anti-NMDA receptor (NMDAR) antibodies (NMDAR-E) is a recently described severe autoimmune neurological disorder, defined by a clinical presentation of encephalitis and presence of IgG targeting the GluN1 subunit of the NMDAR in patients’ cerebrospinal fluid (CSF) [7]
Expression of the NMDAR GluN1 subunit by the teratomatous nervous tissue was significantly more often glial in NMDAR antibodies (NMDAR-E) teratomas than in control teratomas. Another striking particularity was that among these 27 mature teratomas, 3 contained neuroglial tissue exhibiting histopathological features of central nervous system (CNS) neuroglial tumor, while it was exceptionally reported in the literature on sporadic ovarian teratomas ([1, 3, 10, 15, 24, 25, 31–34] the histological classification of these 20 cases is summarized in Additional file 1: Table S2 in Online Resource)
14% of all reported cases are immature which is much greater than sporadic ovarian teratomas; only 3% of the latter are diagnosed as immature, mostly on the presence of immature neural tissue. [4, 22]
Summary
Encephalitis (E) with anti-NMDA receptor (NMDAR) antibodies (NMDAR-E) is a recently described severe autoimmune neurological disorder, defined by a clinical presentation of encephalitis and presence of IgG targeting the GluN1 subunit of the NMDAR in patients’ cerebrospinal fluid (CSF) [7]. An underlying neoplasm is found in 25 to 40% of patients, primarily in young females, and this associated tumor is an ovarian teratoma. Chefdeville et al Acta Neuropathologica Communications neuroglial component have been reported in the recent literature [9, 14]. A marked intratumoral lymphoid infiltrate colocalizing with mature neuroglial elements is reported in a few patients with NMDAR-E but is yet to be fully characterized [6, 9, 14, 19, 27, 30]. We compared ovarian teratomas associated with NMDAR-E to those in patients with sporadic teratomas in order to describe histological features characterizing these tumors
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