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Abstract：
OBJECTIVE: We investigated the clinical significance of thyroid-stimulating hormone receptor (TSHR) mutations detected in thyroid fine needle aspiration (FNA) specimens.
METHODS: The pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations.
RESULTS: A total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty-two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium-iodide transporter (NIS) mRNA was in the range of 0.01%-62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow-up was available in five cases (all benign except one). On follow-up available for 38 cases (mean: 24 months; range: 7-47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size.
CONCLUSIONS: TSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.
METHODS: The pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations.
RESULTS: A total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty-two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium-iodide transporter (NIS) mRNA was in the range of 0.01%-62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow-up was available in five cases (all benign except one). On follow-up available for 38 cases (mean: 24 months; range: 7-47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size.
CONCLUSIONS: TSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.
摘要：
目的：我们研究了甲状腺细针穿刺（FNA）标本中检测到的促甲状腺激素受体（TSHR）突变的临床意义。
方法：我们机构的病理档案在2018年至2021年之间进行了审查，以使用Thyroseq®分析显示TSHR突变的不确定（BethesdaIII和IV类）标本。
结果：共2184例诊断为非典型性/意义不明的滤泡性病变（AUS/FLUS），2625例诊断为滤泡性肿瘤/可疑为滤泡性肿瘤（FN/SFN）。共有1735个AUS/FLUS和2339个SFN/FN接受了Thyroseq®分析；69个显示TSHR突变（1.6%，59女,10男,平均年龄：55岁）。10例表现为嗜酸细胞特征。在FNA的1年内，有12例患者接受了放射性核素扫描：11例功能亢进。结节大小与TSH水平弱相关。鉴定了22种不同的TSHR突变(最常见的:M453T)。在5例中发现了第二个突变（EZH1n=2，EIF1AXn=3）。在所有测序读数中，钠碘转运蛋白（NIS）mRNA的表达在0.01％-62.43％的范围内，49例（71％）升高。手术病理随访5例（除1例外，均为良性）。38例（平均：24个月；范围：7-47个月），34个（89.5％）结节保持稳定，3个（8％）结节大小增加。
结论：甲状腺FNA样本中被分类为不确定的TSHR突变很少见，通常是良性的，并且通常与扫描自主性（如果执行）相关联。
方法：我们机构的病理档案在2018年至2021年之间进行了审查，以使用Thyroseq®分析显示TSHR突变的不确定（BethesdaIII和IV类）标本。
结果：共2184例诊断为非典型性/意义不明的滤泡性病变（AUS/FLUS），2625例诊断为滤泡性肿瘤/可疑为滤泡性肿瘤（FN/SFN）。共有1735个AUS/FLUS和2339个SFN/FN接受了Thyroseq®分析；69个显示TSHR突变（1.6%，59女,10男,平均年龄：55岁）。10例表现为嗜酸细胞特征。在FNA的1年内，有12例患者接受了放射性核素扫描：11例功能亢进。结节大小与TSH水平弱相关。鉴定了22种不同的TSHR突变(最常见的:M453T)。在5例中发现了第二个突变（EZH1n=2，EIF1AXn=3）。在所有测序读数中，钠碘转运蛋白（NIS）mRNA的表达在0.01％-62.43％的范围内，49例（71％）升高。手术病理随访5例（除1例外，均为良性）。38例（平均：24个月；范围：7-47个月），34个（89.5％）结节保持稳定，3个（8％）结节大小增加。
结论：甲状腺FNA样本中被分类为不确定的TSHR突变很少见，通常是良性的，并且通常与扫描自主性（如果执行）相关联。
