GLIS Rearranged Hyalinizing Trabecular Tumor: Is surgery needed?

  • Background: Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with a long-standing controversy regarding its genetic mechanisms, relationship to papillary thyroid carcinoma (PTC), and malignant potential. Recently, PAX8-GLIS fusions, most frequently PAX8-GLIS3, have been reported in the vast majority of HTT but not in PTC, providing strong evidence for distinct pathogenesis of these two tumor types. In this study, we evaluated the prevalence of GLIS fusions in thyroid nodules and correlated it with surgical pathology and outcomes.

    Methods: Prevalence of PAX8-GLIS3 fusions was studied in fine needle aspiration (FNA) samples from thyroid nodules with indeterminate (Bethesda III-V) cytology using ThyroSeq v3 Genomic Classifier.  Surgical pathology reports and clinical follow-up were reviewed.

    Results: Total of 13,703 FNA samples with indeterminate cytology (10,565 AUS/FLUS, 2,016 FN/SFN, 561 SMC) were prospectively studied. 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 follow-up information was available on 6 patients.  All nodules were diagnosed as HTT on surgical pathology, with no invasion or lymph node metastasis found at presentation.

    Conclusions: In this study, we demonstrate that PAX8-GLIS3 fusion can be preoperatively detected in thyroid FNA samples and predict the presence of HTT.  Based on these findings and previous reports demonstrating benign clinical behavior of these tumors, more conservative surgery and possible consideration for active surveillance may be considered for patients with PAX8-GLIS3 fusions detected in thyroid FNA samples, including those with suspicious for malignancy cytology.

 

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