Four distinct ipsilateral vestibular schwannomas: A case of mosaic NF2-related schwannomatosis

• Published in: American journal of clinical pathology Vol. 162; no. 2; pp. 110 - 114
• Main Authors: Tunkel, Alexandra E, Youner, Emily R, Barseghyan, Hayk, Fu, Yulong, Bhattacharya, Surajit, Bornhorst, Miriam, Monfared, Ashkan S
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-08-2024
• Subjects: Adult; Chromosome 22; Cochlea; Ear canal; Female; Gene mapping; Genetic analysis; High-Throughput Nucleotide Sequencing; Humans; Mosaicism; Neurilemmoma - diagnosis; Neurilemmoma - genetics; Neurilemmoma - pathology; Neurofibromatoses - diagnosis; Neurofibromatoses - genetics; Neurofibromatoses - pathology; Neurofibromin 2 - genetics; Neuroma, Acoustic - diagnosis; Neuroma, Acoustic - genetics; Neuroma, Acoustic - pathology; Next-generation sequencing; Schwann cells; Semicircular canals; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tumors; Vestibular system; acoustic neuroma; schwannomatosis; neurofibromatosis 2; vestibular schwannoma; mosaicism
• ISSN: 0002-9173; 1943-7722; 1943-7722
• DOI: 10.1093/ajcp/aqae027

Abstract
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.