Endocrine Practice, Molecular Laboratory, Brueckenstrasse 21, Heidelberg, Germany.
Thyroid. 2013 Mar;23(3):294-300. doi: 10.1089/thy.2012.0236. Epub 2013 Jan 11.
Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC.
Clinical, biochemical, histological, and immunohistological findings, and somatic RET mutations were analyzed, and long-term follow-up was documented.
Seven patients with nonsecretory MTC were identified among 839 patients with sporadic MTC; thus, the prevalence rate of nonsecretory MTC was 0.83%. In these seven patients, Ct and carcinoembryonic antigen (CEA) levels were normal when MTC was initially diagnosed in the patients, despite advanced tumor stage. Ct and CEA levels remained undetectable in four patients; recurrence was indicated in one patient after 10 years of follow-up by routine anatomic imaging and increased CEA levels, and Ct levels became slightly elevated during follow-up, despite massive tumor load, in the remaining two patients. The diagnosis of MTC was confirmed by positive immunohistochemistry for Ct, CEA, and chromogranin A. A high Ki67 proliferation index (PI) (three patients) and a high proportion of RET 918-mutated cells (four patients), as well as poorly differentiated histology, were associated with aggressive biological behavior of the MTC. The prognosis for nonsecretory MTC varied between long-term survival (12.5 years) and rapid progression leading to death within 1.75 years after diagnosis.
The prevalence of nonsecretory MTC was low (0.83% of patients with MTC). Diagnosis was often made at a clinically advanced tumor stage. The histological and immunohistological characteristics and the clinical course and prognosis of nonsecretory MTC are markedly heterogeneous. A high Ki-67 PI and a large proportion of cells with RET 918 mutations are associated with a poor prognosis.
甲状腺髓样癌（MTC）的特征是降钙素（Ct）的合成和分泌。Ct 不分泌的 MTC 曾有少数报道。本研究旨在分析两家治疗 839 例散发性 MTC 患者的三级中心中无分泌性 MTC 的患病率和临床谱。
分析了临床、生化、组织学和免疫组织化学发现以及体细胞 RET 突变，并记录了长期随访结果。
在 839 例散发性 MTC 患者中发现 7 例无分泌性 MTC 患者；因此，无分泌性 MTC 的患病率为 0.83%。在这些 7 例患者中，尽管肿瘤分期较晚，但 MTC 初诊时 Ct 和癌胚抗原（CEA）水平正常。4 例患者 Ct 和 CEA 水平持续未检出；1 例患者在 10 年随访后，常规解剖成像和 CEA 水平升高提示复发，而另外 2 例患者尽管肿瘤负荷巨大，但 Ct 水平在随访期间略有升高。通过 Ct、CEA 和嗜铬粒蛋白 A 的免疫组织化学阳性证实了 MTC 的诊断。3 例患者 Ki67 增殖指数（PI）高，4 例患者 RET918 突变细胞比例高，以及组织学分化差，与 MTC 的侵袭性生物学行为相关。无分泌性 MTC 的预后在长期生存（12.5 年）和诊断后 1.75 年内迅速进展导致死亡之间存在差异。
无分泌性 MTC 的患病率较低（MTC 患者的 0.83%）。诊断通常在临床晚期肿瘤阶段进行。无分泌性 MTC 的组织学和免疫组织化学特征以及临床过程和预后明显不同。高 Ki-67 PI 和大量具有 RET918 突变的细胞与不良预后相关。
