Category: Thyroid

Monitor: 21


Thursday, Apr 25
12:30 PM – 1:00 PM

Objective :

Hyalinizing trabecular tumors (HTT) are rare thyroid neoplasms with controversial genetic mechanisms, relationship to papillary thyroid carcinoma (PTC) and malignant potential. Recently, we reported that PAX8-GLIS fusions, most frequently PAX8-GLIS3, are found in the vast majority of HTT but not in PTC, providing strong evidence for distinct pathogenesis of these two tumor types.  HTT are known to have indolent clinical behavior. In this study, we evaluated the detection of GLIS fusions in thyroid fine needle aspiration (FNA) samples and correlation with surgical pathology and clinical outcomes.

Methods : We studied the prevalence of PAX8-GLIS3 fusions in FNA samples from thyroid nodules with indeterminate (Bethesda III-V) or positive for malignancy (Bethesda VI) cytology using ThyroSeq v3 Genomic Classifier.  Surgical pathology reports and clinical follow-up were reviewed.

Results :

Among 13,703 consecutive FNA samples with indeterminate cytology (10,565 AUS/FLUS, 2,016 FN/SFN, 561 SMC), PAX8-GLIS3 was identified in 14 (0.1%) samples, including 9 (0.09%) nodules with AUS/FLUS cytology, 2 (0.1%) with FN/SFN cytology and 3 (0.53%) nodules with SMC cytology.  PAX8-GLIS3 fusions were 5 times more frequent in samples with SMC category. Surgical pathology and clinical follow-up information was available on 6 patients.  All nodules were diagnosed as HTT on surgical pathology. No lymph node metastasis was found at presentation. On limited clinical follow-up (mean, 65 months), no tumor recurrence was noted. 

Discussion :

Recently, GLIS fusions, and particularly PAX8-GLIS3, were defined as a molecular hallmark of HTT. In this study, we expanded the initial analysis and examined the prevalence of these fusions in a large series of consecutive FNA samples collected from thyroid nodules with indeterminate cytology. Follow-up information obtained on a subset of patients with PAX8-GLIS3 fusions showed that all of them were HTT on final pathology. This information may contribute to the general trend for de-escalation of surgical management of patients with thyroid tumors. 

Conclusion :

In this series of FNA samples with indeterminate cytology, PAX8-GLIS3 fusion was detected in 0.1% of cases and was predictive of HTT. Based on the limited follow-up and previous reports, these tumors demonstrate benign clinical behavior. These findings raise the possibility that active surveillance may be considered for patients with thyroid nodules tested positive for PAX8-GLIS3 fusions, including those with suspicious for malignancy FNA cytology.



Marina N. Nikiforova

Director, Molecular and Genomic Pathology Lab
University of Pittsburgh

Dr. Nikiforova is a Professor of Pathology and Director of the Molecular & Genomic Pathology Laboratory at UPMC where she also serves as the Director of Molecular Oncology Services. She has published 159 peer reviewed articles and serves on multiple committees in the field of Molecular Genomics, including the Association of Molecular Pathology, the College of American Pathologists, and the American Thyroid Association.

Alyaksandr Nikitski

Post-Doctoral Fellow
University of Pittsburgh Medical Center

Post Doctoral Fellow

Federica Panebianco

Post-Doctoral Fellow
University of Pittsburgh

Post-Doctoral Fellow

Cihan Kaya

Bioinformatics Scientist
University of Pittsburgh Medical Center

Bioinformatics Scientist

Yuri E. Nikiforov

Vice Chair, Dept of Pathology.
UPMC, Pennsylvania

Dr. Nikiforov is Professor of Pathology and Vice Chair at the Department of Pathology, University of Pittsburgh where he also serves as Director of the Division of Molecular & Genomic Pathology. He has published over 170 peer-reviewed articles and over 15 book chapters, and is a senior editor of the textbook “Diagnostic Pathology and Molecular Genetics of the Thyroid.” His research program is funded by the National Institute of Health and focused on molecular genetics of thyroid cancer, thyroid cancer diagnostics, and molecular mechanisms of chromosomal rearrangements. He is an elected member of the American Society for Clinical Investigation and a recipient of the 2007 Van Meter Award from the American Thyroid Association, 2014 Light of Light Foundation Honorary Award, 2016 Aldo Pinchera Award from the Italian Thyroid Carcinoma Observatory, and 2017 Sidney H. Ingbar Distinguished Lectureship Award the American Thyroid Association.