1 Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida.
2 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida.
Thyroid. 2018 Feb;28(2):210-219. doi: 10.1089/thy.2017.0419. Epub 2017 Dec 21.
Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios that are generally clustered for analysis and management recommendations. It has been suggested that aspirates exhibiting nuclear atypia have a higher risk of malignancy. This study aimed to assess whether cytologically indeterminate thyroid nodules with nuclear atypia have a significantly higher cancer risk than those without nuclear atypia.
On June 30, 2016, PubMed and EMBASE were searched for articles in English or Spanish using a search strategy developed by an endocrinologist and a librarian. Case reports were excluded, and no date limits were used. The references of all included studies were also screened for relevant missing studies. Studies were included if the prevalences of malignancy of cytologically indeterminate thyroid nodules with histological confirmation with and without nuclear atypia were reported. Studies were excluded if they had: (i) nodules suspicious for malignancy; (ii) nodules with non-indeterminate (B-III or B-IV) cytology on repeated biopsy, if performed; (iii) nodules not consecutively evaluated; or (iv) cohorts overlapping with another larger series. Two investigators independently assessed the eligibility and risk of bias of the studies. PRISMA and MOOSE guidelines were followed. Summary data were extracted from published reports by one investigator and independently reviewed by another. Data were pooled using a random-effects model. Heterogeneity was explored using subgroup analysis and mixed-effect model meta-regression. The odds ratio for malignancy of cytologically indeterminate thyroid nodules with nuclear atypia over cytologically indeterminate thyroid nodules without nuclear atypia was calculated.
Of 2571 retrieved studies, 20 were eligible. The meta-analysis was conducted on summary data of 3532 cytologically indeterminate thyroid nodules: 1162 with and 2370 without nuclear atypia. The odds ratio for malignancy in cytologically indeterminate thyroid nodules with nuclear atypia was 3.63 [confidence interval 3.06-4.35]. There was no evidence of publication bias, and heterogeneity was insignificant (I < 0.01%, p = 0.40).
Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.
甲状腺细胞学不确定类别（Bethesda 系统的 B-III 和 B-IV 类别）由一组异质的细胞学表现组成，通常为了分析和管理建议而聚类。有人认为，具有核异型性的抽吸物恶性风险更高。本研究旨在评估具有核异型性的细胞学不确定甲状腺结节的癌症风险是否明显高于没有核异型性的甲状腺结节。
于 2016 年 6 月 30 日，内分泌学家和图书管理员共同制定检索策略，在 PubMed 和 EMBASE 中检索英文或西班牙文的文章。排除病例报告，且不设日期限制。还对所有纳入研究的参考文献进行筛查，以寻找相关缺失研究。如果报告了组织学证实的细胞学不确定甲状腺结节伴和不伴核异型性的恶性率，则纳入研究。如果研究具有以下情况，则排除在外：（i）恶性可疑的结节；（ii）如果进行了重复活检，则具有非不确定（B-III 或 B-IV）细胞学的结节；（iii）非连续评估的结节；或（iv）与另一个更大系列重叠的队列。两名研究者独立评估研究的纳入标准和偏倚风险。遵循 PRISMA 和 MOOSE 指南。一位研究者从已发表的报告中提取汇总数据，另一位研究者独立进行审查。使用随机效应模型汇总数据。使用亚组分析和混合效应模型荟萃回归探索异质性。计算具有核异型性的细胞学不确定甲状腺结节与不具有核异型性的细胞学不确定甲状腺结节的恶性率之比。
共检索到 2571 项研究，其中 20 项符合纳入标准。对 3532 个细胞学不确定甲状腺结节的汇总数据进行了荟萃分析：1162 个结节伴核异型性，2370 个结节不伴核异型性。具有核异型性的细胞学不确定甲状腺结节的恶性率比为 3.63（95%置信区间 3.06-4.35）。无发表偏倚的证据，异质性不显著（I<0.01%，p=0.40）。
核异型性是细胞学不确定甲状腺结节恶性的一个重要指标，需要标准化并纳入临床实践。
