Teratoma pathology and genomics in anti‐NMDA receptor encephalitis

Abstract Introduction Ovarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to in...

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Main Authors: Yoonhyuk Jang, Kwanghoon Lee, Cheol Lee, Kon Chu, Sang Kun Lee, Jae‐Kyung Won, Soon‐Tae Lee
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.51948
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author Yoonhyuk Jang
Kwanghoon Lee
Cheol Lee
Kon Chu
Sang Kun Lee
Jae‐Kyung Won
Soon‐Tae Lee
author_facet Yoonhyuk Jang
Kwanghoon Lee
Cheol Lee
Kon Chu
Sang Kun Lee
Jae‐Kyung Won
Soon‐Tae Lee
author_sort Yoonhyuk Jang
collection DOAJ
description Abstract Introduction Ovarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe‐associated teratomas and non‐encephalitic control teratomas. Materials and Methods A prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole‐exome sequencing data and pathologic findings between NMDARe‐associated teratomas and control teratomas. Results We found 18 NMDARe‐associated teratomas from 15 patients and compared them with 17 non‐encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non‐encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non‐encephalitic teratomas (n = 18). However, rituximab‐naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non‐encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab‐treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab‐naïve encephalitic teratomas (P = 0.048 and 0.023, respectively). Discussion These results suggest that the initiation of immunopathogenesis in NMDARe‐associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma.
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spelling doaj.art-829c688feec74b75857a0b00c70e7a862024-01-16T18:36:37ZengWileyAnnals of Clinical and Translational Neurology2328-95032024-01-0111122523410.1002/acn3.51948Teratoma pathology and genomics in anti‐NMDA receptor encephalitisYoonhyuk Jang0Kwanghoon Lee1Cheol Lee2Kon Chu3Sang Kun Lee4Jae‐Kyung Won5Soon‐Tae Lee6Department of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Pathology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Pathology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Pathology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaAbstract Introduction Ovarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe‐associated teratomas and non‐encephalitic control teratomas. Materials and Methods A prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole‐exome sequencing data and pathologic findings between NMDARe‐associated teratomas and control teratomas. Results We found 18 NMDARe‐associated teratomas from 15 patients and compared them with 17 non‐encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non‐encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non‐encephalitic teratomas (n = 18). However, rituximab‐naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non‐encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab‐treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab‐naïve encephalitic teratomas (P = 0.048 and 0.023, respectively). Discussion These results suggest that the initiation of immunopathogenesis in NMDARe‐associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma.https://doi.org/10.1002/acn3.51948
spellingShingle Yoonhyuk Jang
Kwanghoon Lee
Cheol Lee
Kon Chu
Sang Kun Lee
Jae‐Kyung Won
Soon‐Tae Lee
Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
Annals of Clinical and Translational Neurology
title Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
title_full Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
title_fullStr Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
title_full_unstemmed Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
title_short Teratoma pathology and genomics in anti‐NMDA receptor encephalitis
title_sort teratoma pathology and genomics in anti nmda receptor encephalitis
url https://doi.org/10.1002/acn3.51948
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