NFATC2::NUTM2 Fusion Defines a Novel Primary Pulmonary Epithelial Tumor With a Distinctive Immunophenotype

作者：Lanlan Feng, Qiao Liu, Xiaoyan Liu, Shumei Wang, J. Li, Yu Han, Xiaorong Mu, Yuanyuan Wang, Junfeng Jiang, Chun Wu, Xiujuan Han, Shaojun Zhu, Fuqin Zhang, Jing Tian, Zhuo Wang, Wei Zhang, Li Gong · 发表于：The American Journal of Surgical Pathology · 年份：2026 · DOI：10.1097/pas.0000000000002533 · 被引用次数：1 · 研究领域：Tuberous Sclerosis Complex Research、Lung Cancer Treatments and Mutations、Congenital Diaphragmatic Hernia Studies

With the application of molecular techniques in pathologic diagnosis, several novel primary pulmonary epithelial tumors have been continuously discovered and classified under the WHO classification of thoracic tumors. Recently, a pulmonary tumor with NFATC2 :: NUTM2B fusion was first documented, but the spectrum of NFATC2::NUTM2 fusion variants and their associated pathologic features remains incompletely characterized. Coincidentally, we also found and described 6 primary pulmonary tumors harboring recurrent NFATC2::NUTM2A/E fusions through integrated genomic analysis. These patients, including 4 females and 2 males, with a median age of 53 years, presented with incidentally detected peripheral lung nodules composed of monotonous epithelioid cells arranged in cords, nests, and trabeculae within a prominent desmoplastic stroma. All tumors exhibited a consistent immunophenotype: CK5/6+/GATA3+/calponin+/EMA+/DOG1 (perinuclear dot-like staining)/p63-. High-throughput chromosome conformation capture (Hi-C) analysis showed the structural variation of NFATC2::NUTM2E in all 6 cases, whereas RNA sequencing detected the fusion transcripts in 5 cases ( NFATC2::NUTM2A , n=2; NFATC2::NUTM2E , n=3). Ultrastructural examination of 1 case suggested epithelial differentiation. All patients remained disease-free after complete resection (median follow-up: 24 mo; range: 9 to 41 mo). These findings define a novel primary pulmonary tumor entity driven by NFATC2::NUTM2 fusions, and characterized ...