Bernardi Stella, Zovato Stefania, Pennelli Gianmaria, Cavallaro Marco, Rovina Matteo, Dobrinja Chiara, Guglielmi Alessandra, Zanconati Fabrizio, Mazzà Daniela, Nieri Alberto, Bartolomei Mirco, Schiavi Francesca
Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Endocrinology Unit (UCO Medicina Clinica), ASUGI, Cattinara Teaching Hospital, Trieste, Italy.
Front Endocrinol (Lausanne). 2025 Mar 27;16:1577421. doi: 10.3389/fendo.2025.1577421. eCollection 2025.
most sympathetic paragangliomas are driven by germline pathogenic variants. Identifying germline succinate dehydrogenase B () pathogenic variant has important management implications. Here we report a novel germline variant in the gene in a patient with metastatic paraganglioma and his response to available treatments.
a 37-year-old Serbian man was admitted to hospital due to hypertension, tachycardia and hyperhidrosis. Screening for secondary hypertension revealed elevated 24-h urinary normetanephrine. A CT scan showed the presence of a 54 x 76 mm retroperitoneal mass that surrounded the aorta, which was located below the pancreas and behind the duodenum. The patient was diagnosed having extra-adrenal sympathetic metastatic paraganglioma (PGL), for which we scheduled debulking surgery and genetic testing. Tumor debulking improved patient symptoms as well as signs of catecholamine excess and tumor mass effects. Meanwhile waiting for next-generation sequencing (NGS) results, the patient started a treatment with sunitinib. At this point, NGS results showed a novel and previously not reported germline c.314T>A gene variant, which was initially classified as a class 3 variant of uncertain significance. Immunohistochemistry for SDHA and SDHB showed absence of SDHB expression and allowed us to reclassify this variant as a class 4 "likely pathogenic" variant. At this stage, due to disease progression and genetic results, sunitinib was stopped and the patient started peptide receptor radionuclide therapy, which was not able to stop disease progression. In the end, the patient was treated with chemotherapy (which is still ongoing), with an amelioration of clinical laboratory and imaging parameters.
Clinical characteristics as well as data from SDHB immunohistochemistry well support reclassification of the novel germline c.314T>A gene variant as a class 4 "likely pathogenic" variant in the patient with metastatic PGL. This information might help clinicians in the management of its carriers and their families. In this case, only debulking surgery and chemotherapy with scheme were clinically effective. Further studies are needed to better clarify and outline at which time point during the disease course patients should start -scheme chemotherapy.
大多数交感神经节旁神经瘤由种系致病性变异驱动。鉴定种系琥珀酸脱氢酶B（SDHB）致病性变异具有重要的管理意义。在此，我们报告一名转移性节旁神经瘤患者中SDHB基因的一种新型种系变异及其对现有治疗的反应。
一名37岁的塞尔维亚男性因高血压、心动过速和多汗症入院。继发性高血压筛查显示24小时尿去甲变肾上腺素升高。CT扫描显示存在一个54×76mm的腹膜后肿块，该肿块围绕主动脉，位于胰腺下方和十二指肠后方。该患者被诊断为肾上腺外交感神经转移性节旁神经瘤（PGL），为此我们安排了减瘤手术和基因检测。肿瘤减瘤改善了患者症状以及儿茶酚胺过量和肿瘤肿块效应的体征。在等待下一代测序（NGS）结果期间，患者开始使用舒尼替尼治疗。此时，NGS结果显示一种新型且先前未报道的种系SDHB c.314T>A基因变异，最初被分类为意义未明的3类变异。SDHA和SDHB的免疫组化显示无SDHB表达，这使我们能够将该变异重新分类为4类“可能致病”变异。在此阶段，由于疾病进展和基因检测结果，停用了舒尼替尼，患者开始接受肽受体放射性核素治疗，但未能阻止疾病进展。最后，患者接受了依托泊苷化疗（仍在进行中），临床实验室和影像学参数有所改善。
临床特征以及SDHB免疫组化数据有力支持将新型种系SDHB c.314T>A基因变异重新分类为转移性PGL患者的4类“可能致病”变异。这些信息可能有助于临床医生对其携带者及其家属进行管理。在本病例中，仅减瘤手术和依托泊苷方案化疗具有临床疗效。需要进一步研究以更好地阐明并确定在疾病过程中的哪个时间点患者应开始依托泊苷方案化疗。
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