Zhou Juan, Duan Miao, Jiao Qiong, Chen Chunyan, Xing Aiyan, Su Peng, Tang Juan, Zhang Hui, Liu Zhiyan
Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Oncol. 2022 Jan 19;11:778296. doi: 10.3389/fonc.2021.778296. eCollection 2021.
Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma.
Ultrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC.
We describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the gene on chromosome 15q14. The NGS results revealed a gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of occurred in the exon region, and the mutation site was 15q14. Moreover, single-nucleotide variation (SNV) occurs in the 3' UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery.
Thyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of gene fusions in addition to the fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.
睾丸核蛋白（NUT）癌（NC）是一种罕见的侵袭性未分化癌，通常起源于膈上中线结构。它由15号染色体q14区域的基因重排独特驱动。甲状腺NC报道较少，且尚无NUT癌的既定治疗指南。
对甲状腺病变进行超声引导下细针穿刺涂片以进行术前诊断。细胞病理学、组织学和免疫化学染色均提示为NC。采用荧光原位杂交（FISH）、定量逆转录聚合酶链反应（qRT-PCR）和二代测序（NGS）分析NC的基因特征。
我们描述了1例38岁男性甲状腺源性NC的罕见病例，具有细胞学、组织学、免疫组织化学和基因特征。细胞涂片和组织病理学标本显示NC的典型特征。免疫组织化学证实与NUT、上皮膜抗原（EMA）、P63、甲状腺转录因子-1（TTF-1）和c-myc呈强免疫反应性。细胞角蛋白19（CK19）仅在突然角化中呈阳性。神经内分泌标志物未发现免疫反应性。应用FISH分离15号染色体q14区域的基因。NGS结果显示一个基因融合，经逆转录定量聚合酶链反应（RT-qPCR）进一步证实。该基因的结构变异（SV）发生在外显子区域，突变位点为15q14。此外，在19号染色体p13.12突变位点的3'非翻译区（UTR）发生单核苷酸变异（SNV）。程序性死亡配体1（PD-L1）联合预测评分超过30%。患者接受化疗，随后用卡瑞利珠单抗进行程序性细胞死亡蛋白1（PD-1）抑制治疗，术后10个月死亡。
甲状腺NC是一种极其罕见且致命的恶性肿瘤。当在细胞学或组织学上观察到鳞状分化时，有必要考虑NC。NGS是获得最终诊断并更好地了解肿瘤发病机制的有效工具。除该融合基因外，大量基因融合可能在NC的发病机制和免疫治疗反应中起作用。由于这种侵袭性恶性肿瘤罕见，NC的免疫治疗仍有待探索。
