Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Cytopathol. 2020 Nov;128(11):812-827. doi: 10.1002/cncy.22374. Epub 2020 Oct 19.
NTRK-rearranged thyroid carcinomas (NRTC), though rare, harbor a potential therapeutic target. The cytomorphologic features by fine needle aspiration (FNA) and the utility of preoperative molecular testing for NRTC remain largely uncharacterized. We provide a detailed cytomorphologic analysis of an institutional NRTC cohort with clinical, radiologic, histopathologic, and molecular correlations.
Our NRTC FNA cohort included 21 specimens from 19 patients. The mean age and female-to-male ratio were 42 years and 2.2:1, respectively. Predominantly alcohol-stained Papanicolaou smears and liquid-based preparations were reviewed for 14 patients with available materials, and histologic review of subsequent resections was conducted for all 19 patients. Imaging and clinical data were accessed through electronic medical records.
Sonographically, NRTC were hypoechoic (87%), predominantly solid (53%) with limited central vascularity (27%), ill-defined borders (67%), and microcalcifications (67%). Observed cytomorphologic features include mixed architectural patterns (79%), fibrosis (93%), oncocytic and vacuolated cytoplasm (36% and 43%, respectively), and abundant intranuclear pseudoinclusions (14%). Most NRTC FNAs were classified as suspicious for malignancy or malignant (89%). One case classified as atypia of uncertain significance underwent ThyroSeq sequencing where a NTRK1 fusion was identified.
Although NRTC did not show a consistent cytomorphologic signature, mixed architectural patterns, prominent fibrosis and distinct cytoplasmic or nuclear features should raise suspicion for NRTC and, when accompanied by negative BRAFV600E by immunohistochemistry on cell block material, aid in selecting cases for molecular testing. This algorithmic approach may help identify potential NRTC, maximizing treatment options for patients, especially in patients for whom treatment planning is complicated.
尽管神经受体酪氨酸激酶（NTRK）重排甲状腺癌（NRTC）较为罕见，但存在潜在的治疗靶点。细针穿刺（FNA）的细胞形态特征以及 NRTC 术前分子检测的实用性在很大程度上仍未得到充分描述。我们提供了一个机构 NRTC 队列的详细细胞形态分析，包括临床、放射学、组织病理学和分子相关性。
我们的 NRTC FNA 队列包括 19 名患者的 21 个标本。平均年龄和男女比例分别为 42 岁和 2.2:1。对 14 名有可用材料的患者进行了主要为酒精染色巴氏涂片和液基制备的回顾性分析，并对所有 19 名患者进行了随后的切除标本的组织学检查。通过电子病历获取影像学和临床数据。
超声表现为 NRTC 呈低回声（87%），主要为实性（53%），中央血管有限（27%），边界不清（67%），微钙化（67%）。观察到的细胞形态特征包括混合性结构模式（79%）、纤维化（93%）、嗜酸细胞和空泡状细胞质（分别为 36%和 43%）和丰富的核内假包涵体（14%）。大多数 NRTC FNA 被归类为恶性或恶性可疑（89%）。一例被归类为意义不确定的非典型性病例进行了 ThyroSeq 测序，其中发现了 NTRK1 融合。
尽管 NRTC 没有显示出一致的细胞形态特征，但混合性结构模式、明显的纤维化和独特的细胞质或核特征应该引起对 NRTC 的怀疑，并且当细胞块材料的免疫组织化学检查显示 BRAFV600E 阴性时，有助于选择进行分子检测的病例。这种算法方法可以帮助识别潜在的 NRTC，为患者最大限度地提供治疗选择，特别是在治疗计划复杂的患者中。
