Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.

N-methyl-D-aspartate receptor antibody production from germinal center reactions: Therapeutic implications.

INTRODUCTION: N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is mediated by immunoglobulin G (IgG) autoantibodies directed against the NR1 subunit of the NMDAR. Around 20% of patients have an underlying ovarian teratoma, and the condition responds to early immunotherapies and ovarian teratoma removal. However, despite clear therapeutic relevance, mechanisms of NR1-IgG production and the contribution of germinal center B cells to NR1-IgG levels are unknown. METHODS: Clinical data and longitudinal paired serum NR1-reactive IgM and IgG levels from 10 patients with NMDAR-antibody encephalitis were determined. Peripheral blood mononuclear cells from these 10 patients, and two available ovarian teratomas, were stimulated with combinations of immune factors and tested for secretion of total IgG and NR1-specific antibodies. RESULTS: In addition to disease-defining NR1-IgG, serum NR1-IgM was found in 6 of 10 patients. NR1-IgM levels were typically highest around disease onset and detected for several months into the disease course. Moreover, circulating patient B cells were differentiated into CD19+ CD27++ CD38++ antibody-secreting cells in vitro and, from 90% of patients, secreted NR1-IgM and NR1-IgG. Secreted levels of NR1-IgG correlated with serum NR1-IgG (p < 0.0001), and this was observed across the varying disease durations, suggestive of an ongoing process. Furthermore, ovarian teratoma tissue contained infiltrating lymphocytes which produced NR1-IgG in culture. INTERPRETATION: Serum NR1-IgM and NR1-IgG, alongside the consistent production of NR1-IgG from circulating B cells and from ovarian teratomas suggest that ongoing germinal center reactions may account for the peripheral cell populations which secrete NR1-IgG. Cells participating in germinal center reactions might be a therapeutic target for the treatment of NMDAR-antibody encephalitis. Ann Neurol 2018;83:553-561.

Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells.

The advantages of using induced pluripotent stem cells (iPSCs) instead of embryonic stem (ES) cells in regenerative medicine centre around circumventing concerns about the ethics of using ES cells and the likelihood of immune rejection of ES-cell-derived tissues. However, partial reprogramming and genetic instabilities in iPSCs could elicit immune responses in transplant recipients even when iPSC-derived differentiated cells are transplanted. iPSCs are first differentiated into specific types of cells in vitro for subsequent transplantation. Although model transplantation experiments have been conducted using various iPSC-derived differentiated tissues and immune rejections have not been observed, careful investigation of the immunogenicity of iPSC-derived tissue is becoming increasingly critical, especially as this has not been the focus of most studies done so far. A recent study reported immunogenicity of iPSC- but not ES-cell-derived teratomas and implicated several causative genes. Nevertheless, some controversy has arisen regarding these findings. Here we examine the immunogenicity of differentiated skin and bone marrow tissues derived from mouse iPSCs. To ensure optimal comparison of iPSCs and ES cells, we established ten integration-free iPSC and seven ES-cell lines using an inbred mouse strain, C57BL/6. We observed no differences in the rate of success of transplantation when skin and bone marrow cells derived from iPSCs were compared with ES-cell-derived tissues. Moreover, we observed limited or no immune responses, including T-cell infiltration, for tissues derived from either iPSCs or ES cells, and no increase in the expression of the immunogenicity-causing Zg16 and Hormad1 genes in regressing skin and teratoma tissues. Our findings suggest limited immunogenicity of transplanted cells differentiated from iPSCs and ES cells.

PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population.

BACKGROUND: PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile. METHODS: This study included 89 pediatric patients receiving standard treatment at Seoul National University Children's Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28. We performed immunohistochemistry assays for PD-1 and PD-L1. To characterize the gene expression, a custom immune-response focused gene panel was used. RESULTS: PD-1 expression was positive in 7 (35%) AT/RT, 7 (35%) EPN, 4 (19%) HGG, and 3 (11%) MBL patients. PD-L1 expression was positive in 8 (40%) AT/RT, 4 (20%) EPN, and 4 (19%) HGG; negative in all MBL patients. There was no statistically significant difference in the overall survival of PD-L1 positive patients. The gene expression analysis demonstrated differences in two clustering functional categories: cell-cell signaling and antigen presentation pathway. CONCLUSIONS: AT/RT, EPN, and HGG showed a relatively higher expression rate of PD-L1 (19-40%). This suggests these tumor types might be good candidates for PD-1 checkpoint blockade. We determined that gene expression may potentially serve as a molecular tool in predicting which patients will respond to immunotherapy. Further investigation is required to better understand the predictive and prognostic role of PD-L1 in pediatric brain tumors.

[Update on anti-N-methyl-D-aspartate receptor encephalitis]. / Update Anti-N-Methyl-D-Aspartat-Rezeptor-Enzephalitis.

Autoimmune encephalitis is a group of autoimmune inflammatory disorders affecting both grey and white matter of the central nervous system. Encephalitis with autoantibodies against the N­methyl-D-aspartate receptor (NMDA-R) is the most frequent autoimmune encephalitis syndrome presenting with a characteristic sequence of psychiatric and neurological symptoms. Treatment necessitates a close interdisciplinary cooperation. This article provides an update on the current knowledge on diagnostic standards, pathogenesis, and treatment strategies for anti-NMDA-R encephalitis from psychiatric and neurological perspectives.

Immunogenicity of induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells. Whereas it has been generally assumed that these autologous cells should be immune-tolerated by the recipient from whom the iPSCs are derived, their immunogenicity has not been vigorously examined. We show here that, whereas embryonic stem cells (ESCs) derived from inbred C57BL/6 (B6) mice can efficiently form teratomas in B6 mice without any evident immune rejection, the allogeneic ESCs from 129/SvJ mice fail to form teratomas in B6 mice due to rapid rejection by recipients. B6 mouse embryonic fibroblasts (MEFs) were reprogrammed into iPSCs by either retroviral approach (ViPSCs) or a novel episomal approach (EiPSCs) that causes no genomic integration. In contrast to B6 ESCs, teratomas formed by B6 ViPSCs were mostly immune-rejected by B6 recipients. In addition, the majority of teratomas formed by B6 EiPSCs were immunogenic in B6 mice with T cell infiltration, and apparent tissue damage and regression were observed in a small fraction of teratomas. Global gene expression analysis of teratomas formed by B6 ESCs and EiPSCs revealed a number of genes frequently overexpressed in teratomas derived from EiPSCs, and several such gene products were shown to contribute directly to the immunogenicity of the B6 EiPSC-derived cells in B6 mice. These findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients. Therefore, the immunogenicity of therapeutically valuable cells derived from patient-specific iPSCs should be evaluated before any clinic application of these autologous cells into the patients.

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma.

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome.

Anti-N-methyl-D-aspartate receptor encephalitis associated with an ovarian teratoma: two cases report and anesthesia considerations.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated syndrome caused by the production of anti-NMDAR receptor antibodies. The syndrome characterised by psychosis, seizures, sleep disorders, hallucinations and short-term memory loss. Ovarian teratoma is the confirmed tumour associated with anti-NMDAR antibodies. The patients with anti-NMDAR encephalitis complicated by ovarian teratoma require surgical treatment under general anesthesia. NMDARs are important targets of many anesthetic drugs. The perioperative management and complications of anti-NMDAR encephalitis, including hypoventilation, paroxysmal sympathetic hyperactivity (PSH) and epilepsy, are challenging for ansthesiologists. CASE PRESENTATION: This report described two female patients who presented for resection of the ovarian teratoma, they had confirmed anti-NMDAR encephalitis accompanied by ovarian teratoma. Two patients received gamma globulin treatments and the resection of the ovarian teratoma under total intravenous anesthesia. They were recovered and discharged on the 20(th) and 46(th) postoperative day respectively. CONCLUSIONS: There is insufficient evidence about the perioperative management, monitoring and anesthesia management of anti-NMDAR encephalitis. This report was based on the consideration that controversial anesthetics that likely act on NMDARs should be avoided. Additionally, BIS monitoring should to be prudently applied in anti-NMDAR encephalitis because of abnormal electric encephalography (EEG). Anesthesiologists must be careful with regard to central ventilation dysfunctions and PSH due to anti-NMDAR encephalitis.

Cytotoxic reaction mediators: granzymes A and B in women with ovarian cancer.

The purpose of this work was the assessment of cytotoxic reaction mediators - granzymes A and B in the serum of women with ovarian tumors. The study included 120 women with proven ovarian tumors. The control group consisted of 60 healthy women in whom no pathological changes within the reproductive system were detected. Concentrations of granzymes A and B were measured by enzyme-linked immunosorbent (ELISA) assay. The highest concentrations of the studied parameters were observed in serum of women with ovarian cancer. Moreover, the concentrations of granzymes A and B in patients with ovarian cancer were substantially increased in comparison to concentrations in patients with ovarian cystadenomas (P < 0.0001) or ovarian teratomas (P < 0.0001).

Immunopathological significance of ovarian teratoma in patients with anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND: The clinical importance of ovarian teratoma in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been established, however investigations of ovarian teratoma in patients with anti-NMDAR encephalitis remain limited. OBJECTIVE: To clarify differences in NMDAR distribution and lymphocyte infiltration in ovarian teratoma between patients with and without anti-NMDAR encephalitis. METHODS: Participants initially comprised 26 patients with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian teratomas were examined using immunopathological techniques. Clinical, laboratory, and radiological data were compared between patients showing the features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal fluid were also measured in encephalitis patients. RESULTS: Neuronal tissues were obtained from ovarian teratomas in 22 patients (after excluding 4 patients who did not satisfy the inclusion criteria), and the presence of NMDA receptor subunits was revealed in all patients. Lymphocyte infiltration was more frequent in the encephalitis group (n = 3) than in the non-encephalitis group. In particular, dense B-lymphocyte infiltration near neural tissues was observed in the encephalitis group. CONCLUSIONS: Differences in lymphocyte infiltration in ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients suggest the immunological importance of the ovarian teratoma as the site of antigen presentation in anti-NMDAR encephalitis.

[Ovarian teratoma associated with anti-N-methyl-D-aspartate receptor encephalitis: a report of 5 cases and review of the literature].

OBJECTIVE: To report the clinical features of ovarian teratoma in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: The clinical information of five female patients with ovarian teratoma and anti-NMDAR encephalitis in Peking Union Medical College Hospital and Beijing Tiantan Hospital affiliated to Capital Medical University from June 2011 to May 2013 were obtained. Relevant literatures were reviewed. RESULTS: The initial symptoms varied from respiratory prodromes or emotional incentives before the onset of psychiatric symptoms. Patients always presented with psychosis, bizarre dyskinesia and seizures. Antibodies to NMDAR in serum and cerebrospinal fluid (CSF) were positive; The psychiatric symptoms were dramatically relieved by tumor reception and immunotherapy which occurred in inverse order of symptom development. No evidence of tumor recurrence was observed during a short-time follow-up after the surgery. CONCLUSIONS: Ovarian teratoma with anti-NMDAR encephalitis always presents with psychiatric symptoms which could be misdiagnosed as psychiatric diseases. Patients respond to tumor resection and immunotherapy.

Human embryonic stem cells suppress T cell responses via arginase I-dependent mechanism.

Human embryonic stem cells (hESCs) can proliferate extensively in culture and give rise to progeny of the three germ layers. Several reports suggested that mouse and hESCs may attenuate immune responses. In this study, we focused on the mechanism by which hESCs inhibit T cell responses. Using coculture experiments, we demonstrate that hESCs inhibit cytokine secretion and T cell proliferation in response to potent T cell activators. Furthermore, we show that hESCs downmodulate the TCR-associated CD3-zeta chain. These effects are maintained when hESCs are replaced by their conditioned media and can be restored by the addition of L-arginine to hESC-conditioned media or by treatment of hESCs with a specific arginase inhibitor. Moreover, we show arginase-I expression and activity in hESCs. We further demonstrate that mouse ESCs (mESCs) similarly inhibit T cell activation via arginase I, suggesting an evolutionary conserved mechanism of T cell suppression by ESCs. In addition, we demonstrate that arginase I expression is not limited to ESCs in culture, but can also be detected in the inner cell mass and the trophectoderm of preimplantation mouse embryos and hESC-derived trophectoderm cells. Finally, T cells infiltrating ESC-derived teratomas have significantly lower levels of CD3-zeta chain. Collectively, the data indicate a role for ESC-arginase I activity in the attenuation of T cell activation.

Reversible paraneoplastic encephalitis in three patients with ovarian neoplasms.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a recently described potentially lethal but treatable disorder that often occurs as a paraneoplastic manifestation of ovarian teratomas. We report three women with this disorder who presented with subacute onset of delirium, seizures and autonomic instability. Anti-NMDA receptor antibodies were detectable in the serum or cerebrospinal fluid of each patient. Ovarian masses were detected in two patients, and subsequently excised. In the third patient, an empirical bilateral salpingo-oophorectomy was performed and revealed a microscopic neoplasm. All patients experienced slow reversal of the neurological symptoms following surgery and immunotherapy. Our experience suggests that prompt syndrome recognition followed by tumor removal and immunotherapy usually results in neurological recovery.

Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells.

Human embryonic stem cells (hESCs) have the capacity to remain pluripotent and self-renew indefinitely. To discover novel players in the maintenance of hESCs, we have previously reported the generation of monoclonal antibodies that bind to cell surface markers on hESCs, and not to mouse embryonic stem cells or differentiated embryoid bodies. In this study, we have identified the antigen target of one such monoclonal antibody as the epithelial cell adhesion molecule (EpCAM). In undifferentiated hESCs, EpCAM is localized to Octamer 4 (OCT4)-positive pluripotent cells, and its expression is down-regulated upon differentiation. To further understand its biological function in hESCs, endogenous EpCAM expression was silenced using small interfering RNA. EpCAM knockdown had marginal negative effects on OCT4 and TRA-1-60 expression, however cell proliferation was decreased by >40%. Examination of lineage marker expression showed marked upregulation of endoderm and mesoderm genes in EpCAM-silenced cells, under both pluripotent and differentiating conditions. These results were validated using a hESC line whose EpCAM expression has been stably knocked down. Data from the stable line confirmed that downregulation of EpCAM decreases cell growth and increases gene expression in the endoderm and mesoderm lineages. In vivo, hESCs lacking EpCAM were able to form teratomas containing tissues representing the three germ layers, and gene expression analysis yielded marked increase in the endoderm marker alpha fetoprotein compared with control. Together these data demonstrate that EpCAM is a surface marker on undifferentiated hESCs and plays functional roles in proliferation and differentiation.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. CASE PRESENTATION: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. CONCLUSIONS: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

NMDA receptor antibody encephalitis.

N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is a recently described immunotherapy-responsive panencephalitis with characteristic features that include a psychiatric onset and a later movement disorder. This entity was first described as a paraneoplastic phenomenon in young women with ovarian teratomata. However, more recently it has become clear that the majority of patients, particularly children, do not harbor a tumor and that males can also be affected. With the development of the NMDAR antibody assay, now available worldwide, a few patients with classical limbic encephalitis and early psychosis and epilepsy have also been found to harbor these antibodies. Early diagnosis followed by immunotherapies and tumor removal, when relevant, expedite recovery from the condition. Antibody levels correlate with the clinical severity of the disease in individual patients, and the antibodies have been shown to substantially reduce NMDA receptors on hippocampal neurons both in vitro and in vivo, supporting the likely direct pathogenicity of the NMDAR antibodies.

Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET.

PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells. EXPERIMENTAL DESIGN: Delta-24-RGD determinants for infection and replication were evaluated in patient expression datasets. Viral replication and cytotoxicity were assessed in vitro in a battery of CNS-PNET and AT/RT cell lines. In vivo, efficacy was determined in different orthotopic mouse models, including early and established tumor models, a disseminated AT/RT lesion model, and immunocompetent humanized mouse models (hCD34+-NSG-SGM3). RESULTS: Delta-24-RGD infected and replicated efficiently in all the cell lines tested. In addition, the virus induced dose-dependent cytotoxicity [IC50 value below 1 plaque-forming unit (PFU)/cell] and the release of immunogenic markers. In vivo, a single intratumoral Delta-24-RGD injection (107 or 108 PFU) significantly increased survival and led to long-term survival in AT/RT and PNET models. Delta-24-RGD hindered the dissemination of AT/RTs and increased survival, leading to 70% of long-term survivors. Of relevance, viral administration to established tumor masses (30 days after engraftment) showed therapeutic benefit. In humanized immunocompetent models, Delta-24-RGD significantly extended the survival of mice bearing AT/RTs or PNETs (ranging from 11 to 27 days) and did not display any toxicity associated with inflammation. Immunophenotyping of Delta-24-RGD-treated tumors revealed increased CD8+ T-cell infiltration. CONCLUSIONS: Delta-24-RGD is a feasible therapeutic option for AT/RTs and CNS-PNETs. This work constitutes the basis for potential translation to the clinical setting.

Paraneoplastic AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder Associated With Teratoma: A Case Report and Literature Review.

OBJECTIVES: To assess a case of paraneoplastic aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive neuromyelitis optica spectrum disorder (NMOSD) associated with teratoma and determine whether it is a paraneoplastic neurologic disorder. METHODS: A single case study and literature review of 5 cases. RESULTS: A 27-year-old woman presented with diplopia, facial nerve palsy, paraplegia, sensory dysfunction of lower limbs, dysuria, nausea, and vomiting. Spinal cord MRI detected an extensive longitudinal lesion in the spinal cord, and brain MRI detected abnormal lesions in the right cerebral peduncle and tegmentum of the pons. CSF analysis revealed positive oligoclonal IgG bands (OCBs). The patient tested positive for AQP4-IgG, confirming a diagnosis of NMOSD. An abdominal CT scan detected an ovarian tumor. After steroid therapy and tumor removal, the patient progressively improved, with only mild sensory dysfunction. Histopathologic analysis of the tumor revealed a teratoma and the presence of glial fibrillary acidic protein (GFAP)+ neural tissue with AQP4 immunoreactivity, accompanied by lymphocyte infiltration. Including the present case, there have been 6 reported cases of AQP4-IgG-seropositive NMOSD associated with ovarian teratoma (mean onset age, 32.7 years). Of these patients, 5 (83%) presented with nausea and/or vomiting, positive OCB, and dorsal brainstem involvement. Pathologic analyses of the teratoma were available in 5 cases, including the present case, revealing neural tissue with AQP4 immunoreactivity and lymphocyte infiltration in all cases. CONCLUSIONS: This study suggests that ovarian teratoma may trigger the development of AQP4-IgG-seropositive NMOSD. Further studies are needed to elucidate the pathogenesis of teratoma-associated NMOSD.