CASE REPORT article
Front. Med.
Sec. Pathology
This article is part of the Research TopicPathology in Personalised Oncology: Biomarkers, Predictive Models, and Therapeutic TargetsView all articles
Membranous/Cytoplasmic Ki-67 Staining and PAX8-GLIS3 Fusion: Defining the Clinicopathological Spectrum of Hyalinizing Trabecular Tumor to Optimize Patient Management
Provisionally accepted
Haining Huang
Ran ZhaoLiman ZhangShujun RenJianli LiuDandan YangJunjun ZhangRenya Zhang
Shuai Chen*
Lei Li*- Affiliated Hospital of Jining Medical University, Jining, China
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Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with an excellent prognosis, yet its morphological resemblance to malignancies such as papillary thyroid carcinoma (PTC) often complicates diagnosis. To characterize the clinicopathological, immunohistochemical, and molecular profiles of HTT, this study analyzed 21 HTT cases and 10 PTC cases, with findings supplemented by a literature review. The HTT cohort included 18 females and 3 males, with a mean age of 51 years. Cytologically, HTT can be distinguished from PTC by its distinctive membranous/cytoplasmic Ki-67 staining pattern, the presence of PAX8-GLIS3 gene fusion, and occasional polyploid cells. Histologically, the tumors were well-demarcated and exhibited trabecular or organoid growth, eosinophilic to granular cytoplasm, paranuclear yellow inclusions, and hyalinized stroma. Immunohistochemically, HTT consistently expressed TG, TTF1, and CD56, while Ki-67 showed a unique membranous/cytoplasmic distribution. Molecular profiling identified no KRAS, NRAS, BRAF, or PIK3CA mutations; however, PAX8-GLIS3 fusion was detected in all HTT cases—a finding absent in PTC. The use of Ki-67 immunohistochemistry or PAX8-GLIS3 testing on cytological specimens can aid in definitive diagnosis and prevent unnecessary surgery. Thus, an integrated approach combining cytological, histological, immunohistochemical, and molecular data is essential for the accurate diagnosis and optimal clinical management of HTT.
Keywords: BRAF, Clinicopathological feature, Hyalinizing trabecular tumor, Ki-67, Papillary thyroid carcinoma, PAX8-GLIS3 fusion
Received: 09 Dec 2025; Accepted: 27 Jan 2026.
Copyright: © 2026 Huang, Zhao, Zhang, Ren, Liu, Yang, Zhang, Zhang, Chen and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shuai Chen
Lei Li
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