DataSheet_1_Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.pdf

BackgroundParagangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL.
Case reportWe report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB.
ConclusionThis case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

背景
副神经节瘤（Paragangliomas, PGL）是一类源自自主神经系统副神经节的罕见神经内分泌肿瘤。膀胱副神经节瘤（Urinary Bladder Paragangliomas, UBPGL）起源于膀胱壁的交感神经元，占所有副神经节瘤的0.7%，占所有膀胱肿瘤的比例不足0.05%。PGL与UBPGL可与SDHB、SDHD、NF1及VHL基因变异相关，其中最常见的种系变异见于SDHB和VHL基因。
病例报告
本病例报告一例42岁女性患者，临床表现为月经过多/血尿、子宫平滑肌瘤，同时合并心脏及膀胱肿物。根据临床检查结果，心脏肿物初步考虑为黏液瘤，而膀胱肿物经诊断为UBPGL。在UBPGL组织中检测到一种新型SDHB突变（c.642G>A, p Q214Q），经证实为体细胞突变。尽管该变异看似为同义突变，但因其剪接位点效应被预测存在功能丧失；免疫组化检测显示SDHB蛋白缺失，进一步支持了这一结论。
结论
本病例凸显了诊断极为罕见的膀胱副神经节瘤所面临的挑战，强调需采用多学科诊疗策略，以甄别最初可能具有误导性的各类临床及影像学表现。此外，本研究报告了一种可被误认为同义突变而被忽视的新型SDHB功能丧失变异，同时阐明了种系与体细胞突变检测的重要性。