Elena Rapizzi, Lorenzo Zanatta, Alice Santi, Fabio Staderini, Niccolò Galeotti, Tonino Ercolino, Francesca Amore, Clotilde Sparano, Mario Maggi, Letizia Canu
{"title":"Presurgical Succinate MetAstatic Risk Tool (P-SMART) in Paragangliomas.","authors":"Elena Rapizzi, Lorenzo Zanatta, Alice Santi, Fabio Staderini, Niccolò Galeotti, Tonino Ercolino, Francesca Amore, Clotilde Sparano, Mario Maggi, Letizia Canu","doi":"10.1007/s12022-025-09878-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Paragangliomas (PGLs) are rare malignant non-epithelial neuroendocrine neoplasms characterized by a strong genetic determinism and heterogeneous metastatic potential with no reliable histopathological predictors. In this retrospective study we investigated the role of serum succinate as a biomarker for metastatic risk and developed a novel preoperative scoring tool.</p><p><strong>Matherials and methods: </strong>Seventy patients with PGLs evaluated between 2006 and 2023 were analysed. Clinical, biochemical, imaging, and genetic data were collected. Germline genetic variants were analysed via Sanger sequencing or NGS through a targeted panel of susceptibility genes. Serum succinate concentrations were quantified by gas chromatography-mass spectrometry.</p><p><strong>Results: </strong>Succinate levels were significantly higher in patients with Cluster 1 genetic variants (p < 0.001), extra-adrenal PGLs (p = 0.006), and metastatic disease (p = 0.024). We developed a novel preoperative risk assessment tool, the P-SMART (Preoperative Succinate MetAstatic Risk Tool), combining serum succinate levels, tumour size, and location. P-SMART assigns: 3 points for extra-adrenal localization, 3.5 points for serum succinate ≥ 8.95 µM, and 3 points for tumour size ≥ 7.0 cm. In our cohort a P-SMART score > 4.75 predicted metastatic disease with 72.7% sensitivity and 83% specificity, outperforming the ASES score (Age, Size, Extra-adrenal, Secretory type; AUC 0.891 vs 0.752, p = 0.005).</p><p><strong>Conclusions: </strong>Though limited by sample size and retrospective design, our findings suggest that succinate is a minimally invasive biomarker that could enhance preoperative metastatic risk stratification, especially when integrated into a multiparametric score such as P-SMART. Larger prospective studies are needed to validate its role, but P-SMART could optimize clinical decision-making, refine patient selection for whole-body imaging, reduce unnecessary radiation exposure, and inform surveillance strategies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"33"},"PeriodicalIF":4.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484271/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12022-025-09878-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Paragangliomas (PGLs) are rare malignant non-epithelial neuroendocrine neoplasms characterized by a strong genetic determinism and heterogeneous metastatic potential with no reliable histopathological predictors. In this retrospective study we investigated the role of serum succinate as a biomarker for metastatic risk and developed a novel preoperative scoring tool.
Matherials and methods: Seventy patients with PGLs evaluated between 2006 and 2023 were analysed. Clinical, biochemical, imaging, and genetic data were collected. Germline genetic variants were analysed via Sanger sequencing or NGS through a targeted panel of susceptibility genes. Serum succinate concentrations were quantified by gas chromatography-mass spectrometry.
Results: Succinate levels were significantly higher in patients with Cluster 1 genetic variants (p < 0.001), extra-adrenal PGLs (p = 0.006), and metastatic disease (p = 0.024). We developed a novel preoperative risk assessment tool, the P-SMART (Preoperative Succinate MetAstatic Risk Tool), combining serum succinate levels, tumour size, and location. P-SMART assigns: 3 points for extra-adrenal localization, 3.5 points for serum succinate ≥ 8.95 µM, and 3 points for tumour size ≥ 7.0 cm. In our cohort a P-SMART score > 4.75 predicted metastatic disease with 72.7% sensitivity and 83% specificity, outperforming the ASES score (Age, Size, Extra-adrenal, Secretory type; AUC 0.891 vs 0.752, p = 0.005).
Conclusions: Though limited by sample size and retrospective design, our findings suggest that succinate is a minimally invasive biomarker that could enhance preoperative metastatic risk stratification, especially when integrated into a multiparametric score such as P-SMART. Larger prospective studies are needed to validate its role, but P-SMART could optimize clinical decision-making, refine patient selection for whole-body imaging, reduce unnecessary radiation exposure, and inform surveillance strategies.
副神经节瘤（PGLs）是一种罕见的恶性非上皮性神经内分泌肿瘤，其特点是具有很强的遗传决定性和异质性转移潜力，没有可靠的组织病理学预测因子。在这项回顾性研究中，我们研究了血清琥珀酸盐作为转移风险的生物标志物的作用，并开发了一种新的术前评分工具。材料与方法：对2006 ~ 2023年间70例经评估的pgl患者进行分析。收集临床、生化、影像学和遗传学资料。生殖系遗传变异通过Sanger测序或NGS通过目标易感基因面板进行分析。采用气相色谱-质谱法测定血清琥珀酸盐浓度。结果：琥珀酸盐水平在集群1遗传变异患者中显著升高(p 4.75预测转移性疾病，敏感性为72.7%，特异性为83%，优于ASES评分（年龄、体型、肾上腺外、分泌型；AUC 0.891 vs 0.752, p = 0.005）。结论：虽然受样本量和回顾性设计的限制，我们的研究结果表明琥珀酸盐是一种微创生物标志物，可以增强术前转移风险分层，特别是当与P-SMART等多参数评分相结合时。需要更大规模的前瞻性研究来验证其作用，但P-SMART可以优化临床决策，优化患者全身成像选择，减少不必要的辐射暴露，并为监测策略提供信息。
期刊介绍：
Endocrine Pathology publishes original articles on clinical and basic aspects of endocrine disorders. Work with animals or in vitro techniques is acceptable if it is relevant to human normal or abnormal endocrinology. Manuscripts will be considered for publication in the form of original articles, case reports, clinical case presentations, reviews, and descriptions of techniques. Submission of a paper implies that it reports unpublished work, except in abstract form, and is not being submitted simultaneously to another publication. Accepted manuscripts become the sole property of Endocrine Pathology and may not be published elsewhere without written consent from the publisher. All articles are subject to review by experienced referees. The Editors and Editorial Board judge manuscripts suitable for publication, and decisions by the Editors are final.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
