Binter Teresa, Niederle Martin Bruno, Arikan Melisa, Hargitai Lindsay, Schernthaner-Reiter Marie Helene, Baumgartner-Parzer Sabina, Niederle Bruno, Scheuba Christian, Riss Philipp
Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria.
Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
Gland Surg. 2025 Jun 30;14(6):1033-1041. doi: 10.21037/gs-2025-130. Epub 2025 Jun 26.
Patients with rearranged-during-transfection () mutations may develop aggressive medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT) within the multiple endocrine neoplasia 2 (MEN2) syndrome, depending on the specific genotype. The Y791F variant has been subject to studies over time but opinions on how to deal with it differ. Pathogenicity could never be proven, nor entirely ruled out. This study aims to contribute to the assessment of its importance and necessity for clinical surveillance.
Thirty-six patients with a pathogenic variant in codon Y791F were analysed in this retrospective clinical and biochemical follow-up study in terms of their clinical manifestation. The patients were diagnosed within a prospective calcitonin screening program of individuals with thyroid nodules, PCC and/or PHPT.
MTC was diagnosed in three index cases of patients aged between 56 and 69 years. Beside thyroid nodules, neoplastic C-cell hyperplasia (nCCH) was diagnosed in five index cases, aged between 48 and 69 years. One index patient presented with unilateral PCC at the age of 68 years and another with PHPT at the age of 54 years. The patients were longitudinally monitored for a median [min-max] of 101.5 [0-263] months from the time of mutation diagnosis to the last follow-up, thereby encompassing observation until reaching a median [min-max] age of 56.5 [18-82] years, assuming a lifelong condition.
Despite perceptions of clinical insignificance, ongoing uncertainties regarding potential clinical manifestations of MEN2 continue to surround the Y791F variant. There is an ambiguity between sporadic cases and MEN2 associated manifestations leaving the role of regular monitoring open for consideration.
在多发性内分泌腺瘤2型（MEN2）综合征中，转染期间重排（RET）基因突变的患者可能会根据特定基因型发展为侵袭性甲状腺髓样癌（MTC）、嗜铬细胞瘤（PCC）和原发性甲状旁腺功能亢进症（PHPT）。随着时间的推移，Y791F变异体一直受到研究，但对于如何处理它的意见存在分歧。其致病性从未得到证实，也从未被完全排除。本研究旨在为评估其对临床监测的重要性和必要性做出贡献。
在这项回顾性临床和生化随访研究中，对36例密码子Y791F存在致病变异的患者的临床表现进行了分析。这些患者是在一项针对甲状腺结节、PCC和/或PHPT个体的前瞻性降钙素筛查项目中被诊断出来的。
在3例年龄在56至69岁之间的索引病例中诊断出MTC。除甲状腺结节外，在5例年龄在48至69岁之间的索引病例中诊断出肿瘤性C细胞增生（nCCH）。1例索引患者在68岁时出现单侧PCC，另1例在54岁时出现PHPT。从突变诊断到最后一次随访，患者的纵向监测中位时间为101.5[0-263]个月，从而涵盖了直到达到中位年龄56.5[18-82]岁（假设为终身情况）的观察期。
尽管认为其临床意义不大，但关于MEN2潜在临床表现的不确定性仍然围绕着Y791F变异体。散发性病例和MEN2相关表现之间存在模糊性，使得定期监测的作用有待考虑。
