Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France.
University of Lille, Lille, France.
Eur Thyroid J. 2022 Dec 22;12(1). doi: 10.1530/ETJ-22-0111. Print 2023 Feb 1.
Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets.
Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair-gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages.
We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.
间变性甲状腺癌(ATC)是甲状腺癌中最具侵袭性的一种,预后极差。尽管预后较好的病例较为少见,但有助于解析分子病理生理学、研究预后因素和发现新的治疗靶点。
两名患者被诊断为局部晚期不可切除的 ATC,其中一名患者发生了转移性扩展。每位患者均接受了化疗和放疗,从而使甲状腺得以进行手术切除。在两种情况下,病理检查均显示完全缓解,无存活肿瘤细胞。随访 48 个月和 70 个月后,两名患者均未出现疾病复发。对甲状腺活检的分子探索显示微卫星不稳定性(MSI)和错配修复基因复合物改变,两种情况下均存在 PTEN 和 ATM 变异。此外,两种情况还存在非典型免疫浸润,由相等比例的 T CD4+淋巴细胞和巨噬细胞组成。
我们报告了两例晚期 ATC 治愈的病例,并首次在这一背景下进行了遗传和免疫学探索。这两例病例似乎表明 MSI-ATC 可能预示着更好的预后。我们的研究假设存在不同的负责机制,包括对放化疗的敏感性增加和/或免疫肿瘤浸润的调节。