Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2′-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.

头颈副神经节瘤 (HNPGLs) 是一种罕见的化疗耐药肿瘤，只能通过手术治愈，受遗传易感性的强烈影响，因此由于新发疾病的风险，患者和亲属需要终生随访 MRI 和/或 PET-CT。这需要暴露于电磁/电离辐射、成本和组织挑战，因为患者和亲属分散在远离参考中心的地方。需要简化的一线筛查策略。我们采用流动注射分析串联质谱法，用于新生儿代谢筛查，比较 HNPGL 患者（59 个样本，56 例）和健康对照（24 个样本，24 例）的血浆代谢特征。主成分分析 (PCA) 和偏最小判别分析 (PLS-DA) 突出显示了独特的 HNPGL 签名，可能反映了 TCA 循环向谷氨酰胺分解和支链氨基酸分解代谢的回补转化、DNA 损伤和脱氧腺苷 (dAdo) 积累、脂肪酸氧化受损、转向 Warburg 效应和促炎性溶血磷脂酰胆碱 (LPC) 信号传导。对 PLS-DA 影响最大的代谢物的统计分析扩展到 10 名听神经瘤和 2 名胆脂瘤患者，证实了与 HNPGL 血浆代谢组学特征相关的显着差异。基于 2 种代谢物 dAdo 和 C26:0-LPC 构建的 ROC 曲线的最佳混淆矩阵提供了 94.29% 的特异性和 89.29% 的敏感性，阳性和阴性预测值分别为 96.2% 和 84.6%。干静脉血和毛细血管血中 dAdo 和 C26:0-LPC 水平的分析证实 dAdo、