Abstract：
The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of \"high-grade\" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.
摘要：
甲状腺结节的分类，特别是那些有卵泡生长模式的人，有显著的进化。这些肿瘤，富含RAS或RAS样突变，由于核异型等变量，病理学家仍然具有挑战性，入侵,有丝分裂活性，和肿瘤坏死。这篇综述讨论了良性的组织学相关性，低风险,和恶性RAS突变甲状腺肿瘤，以及一些难以分类的滤泡结节，其特征令人担忧。一个典型的RAS突变结节是具有乳头状样细胞核特征（NIFTP）的非侵入性滤泡性甲状腺肿瘤。对包封/界限明确的非侵入性RAS突变滤泡型肿瘤的核特征的评估有助于区分滤泡性甲状腺腺瘤（FTA）和NIFTP。尽管这个简单的概念，关于NIFTP诊断所需的核异型性程度的问题在临床实践中很常见.滤泡结节的命名法缺乏明确的侵袭性特征，有丝分裂活动增加，肿瘤坏死,和/或高风险突变(例如，TERT启动子或TP53）仍然存在争议。入侵,特别是血管浸润，是RAS突变的滤泡样肿瘤中恶性肿瘤的当前标志，以滤泡性甲状腺癌(FTC)为模子。评估肿瘤界面至关重要，虽然完整的胶囊评估可能是具有挑战性的。多水平和NRASQ61R特异性免疫组织化学可以帮助识别侵袭。围绕血管浸润的争议持续存在，带有辅助污渍，如CD31，ERG，和CD61协助其评估。此外，该综述强调浸润性囊化滤泡型乳头状甲状腺癌（IEFVPTC）与FTC密切相关，这表明需要更好的命名法。“高级别分化癌”的概念，适用于具有坏死和/或高有丝分裂活性的FTC或IEFVPTC，也讨论了。
