Alexandra E Tunkel, Emily R Youner, Hayk Barseghyan, Yulong Fu, Surajit Bhattacharya, Miriam Bornhorst, Ashkan S Monfared
{"title":"四个不同的同侧前庭分裂瘤:一例镶嵌型 NF2 相关分裂瘤病。","authors":"Alexandra E Tunkel, Emily R Youner, Hayk Barseghyan, Yulong Fu, Surajit Bhattacharya, Miriam Bornhorst, Ashkan S Monfared","doi":"10.1093/ajcp/aqae027","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.</p><p><strong>Methods: </strong>We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).</p><p><strong>Results: </strong>Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\"first hit\") but distinct \"second hit\" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.</p><p><strong>Conclusions: </strong>Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"110-114"},"PeriodicalIF":2.3000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Four distinct ipsilateral vestibular schwannomas: A case of mosaic NF2-related schwannomatosis.\",\"authors\":\"Alexandra E Tunkel, Emily R Youner, Hayk Barseghyan, Yulong Fu, Surajit Bhattacharya, Miriam Bornhorst, Ashkan S Monfared\",\"doi\":\"10.1093/ajcp/aqae027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.</p><p><strong>Methods: </strong>We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).</p><p><strong>Results: </strong>Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\\\"first hit\\\") but distinct \\\"second hit\\\" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.</p><p><strong>Conclusions: </strong>Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.</p>\",\"PeriodicalId\":7506,\"journal\":{\"name\":\"American journal of clinical pathology\",\"volume\":\" \",\"pages\":\"110-114\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of clinical pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ajcp/aqae027\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of clinical pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ajcp/aqae027","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
Four distinct ipsilateral vestibular schwannomas: A case of mosaic NF2-related schwannomatosis.
Objectives: Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.
Methods: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).
Results: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors ("first hit") but distinct "second hit" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.
Conclusions: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.
期刊介绍:
The American Journal of Clinical Pathology (AJCP) is the official journal of the American Society for Clinical Pathology and the Academy of Clinical Laboratory Physicians and Scientists. It is a leading international journal for publication of articles concerning novel anatomic pathology and laboratory medicine observations on human disease. AJCP emphasizes articles that focus on the application of evolving technologies for the diagnosis and characterization of diseases and conditions, as well as those that have a direct link toward improving patient care.