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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797353814514204672 |
---|---|
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. |
first_indexed | 2024-03-08T13:35:29Z |
format | Article |
id | doaj.art-829c688feec74b75857a0b00c70e7a86 |
institution | Directory Open Access Journal |
issn | 2328-9503 |
language | English |
last_indexed | 2024-03-08T13:35:29Z |
publishDate | 2024-01-01 |
publisher | Wiley |
record_format | Article |
series | Annals of Clinical and Translational Neurology |
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 |
work_keys_str_mv | AT yoonhyukjang teratomapathologyandgenomicsinantinmdareceptorencephalitis AT kwanghoonlee teratomapathologyandgenomicsinantinmdareceptorencephalitis AT cheollee teratomapathologyandgenomicsinantinmdareceptorencephalitis AT konchu teratomapathologyandgenomicsinantinmdareceptorencephalitis AT sangkunlee teratomapathologyandgenomicsinantinmdareceptorencephalitis AT jaekyungwon teratomapathologyandgenomicsinantinmdareceptorencephalitis AT soontaelee teratomapathologyandgenomicsinantinmdareceptorencephalitis |