Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.
目的： 探讨鼻咽部甲状腺样低级别乳头状腺癌（TL-LGNPPA）的临床和病理学特征、免疫表型及相关基因改变。 方法： 收集2011年11月至2020年8月浙江省肿瘤医院（5例）和浙江大学医学院附属第一医院（10例）的15例TL-LGNPPA病例，对其进行临床和病理学观察、免疫组织化学染色及二代测序，总结其临床病理和分子生物学特点，并进行相关文献复习。 结果： 15例患者中位年龄36岁（20~60岁），男性7例，女性8例。最常见的症状是鼻出血和鼻塞，肿瘤主要位于鼻咽顶和鼻中隔后缘。病理形态学特征包括：由单层或假复层立方、柱状细胞构成复杂的乳头状及腺样结构，瘤细胞轻-中度异型。部分病例瘤细胞梭形，并与上皮细胞移行；可见核沟、磨玻璃样核，鳞状上皮化生，或间质散在沙砾体。此外，部分病例存在核极性反转细胞、靴钉样细胞及微乳头状结构。免疫组织化学染色结果显示所有病例肿瘤细胞甲状腺转录因子1（TTF1）、细胞角蛋白（CK）7、波形蛋白和广谱细胞角蛋白弥漫阳性；少数病例p40、CK5/6和p16部分细胞阳性；甲状腺球蛋白、Napsin A、CK20、CDX2、S-100蛋白和PAX8均阴性。Ki-67阳性指数1%~20%，其中≤10%有13例。EB病毒编码的RNA（EBER）原位杂交均阴性。6例标本进行了DNA序列检测，结果发现存在不同的基因突变（EWSR1、SMAD2、ROS1、JAK3、GRIN2A、ERRCC5、STAT3、TET2），未找到热点基因改变；同时都为低肿瘤突变负荷，也未检出胚系基因突变、微卫星高度不稳定和DNA错配修复相关基因改变。所有患者行内镜手术治疗，其中1例术后加放疗，随访23~129个月均无瘤生存。 结论： TL-LGNPPA是一种鼻咽部少见的惰性肿瘤，具有独特的形态学和免疫表型。TL-LGNPPA患者预后较好，内镜下完整切除是治疗该肿瘤的有效方法。.