Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well as limited or reduced nuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed as TBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reduced PTC nuclear features with respect to nuclear elongation and chromatin alterations compared to those typically identified in “BRAF-like” PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the “RAS-like” nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

间变性淋巴瘤激酶( ALK ) 基因融合在甲状腺乳头状癌 (PTC) 中很少见，但可以作为治疗靶点。本研究旨在评估来自我们的病理档案和会诊的一系列 8 个ALK重排 PTC 的术前细胞学结果和临床病理特征。所有病例均通过 ALK D5F3 免疫组织化学证实，其中 6 例病例还通过基于 RNA 的靶向下一代测序 (NGS) 进行了确认。最初的细针抽吸 (FNA) 细胞学诊断包括 3 例 (37.5%) 为 Bethesda 系统 (TBS) II 类、2 例 (25%) 为 TBS III、2 例 (25%) 为 TBS V、1 例为 TBS VI。 （12.5%）。六例患者具有可用的 FNA 细胞学检查并进行了审查。细胞学特征显示所有六种细胞均具有微滤泡结构以及有限或减少的核伸长和染色质改变。 2 例不存在核沟和假包涵体，3 例很少或集中发现核沟和假包涵体，1 例经常出现。两例最初诊断为 TBS II 的病例，显示微滤泡结构，无发育良好的核特征，被修改为 TBS III（仅具有结构异型性）。对于组织学相关性，四种为浸润性滤泡变异型 PTC，三种为以滤泡生长为主的经典亚型 PTC，一种为实性/小梁亚型 PTC。与“ BRAF样”PTC中典型的特征相比，所有 8 个病例均表现出在核伸长和染色质改变方面的 PTC 核特征减少。 NGS 测试显示EML4::ALK融合为 3 个，STRN::ALK融合为 2 个，ITSN2::ALK融合为 1 个。总之，虽然从BRAF-RAS评分的角度来看， ALK重排的 PTC 与中性基因表达谱相关，但“ RAS样”核特征在该系列中更常见，导致术前 FNA 经常出现不确定诊断。