Hyalinizing trabecular tumor of the thyroid: Interest of GLIS3 immunohistochemical study to detect PAX8::GLIS3 rearrangement.

BACKGROUND

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Objective

Hyalinizing trabecular tumor of the thyroid (HTT) is a rare, low-risk neoplasm that poses diagnostic challenges. Very recently, PAX8::GLIS3 rearrangements were found to characterize HTT. We aimed to explore HTT's genetic profile, focusing on PAX8::GLIS3 rearrangements and GLIS3 immunohistochemical staining.

METHODS

We conducted a retrospective study involving 8 cases histologically diagnosed as HTT. RNA sequencing and immunohistochemical staining for GLIS3 were performed on all cases.

RESULTS

The study included five females and three males, with a tumor size ranging from 3 to 45 mm. RNA sequencing analysis showed PAX8::GLIS3 rearrangement in 6 cases (86 %). No other molecular alterations were found. However, one case failed due to the tissue quality, and one case did not show any gene fusion. Immunohistochemical staining for GLIS3 revealed nuclear positive expression in tumor cells for all cases where gene fusion was detected (100 %). A control group of 20 HTT mimickers showed no immunostaining for GLIS 3.

CONCLUSION

Our study confirms the consistent presence of PAX8::GLIS3 rearrangement in hyalinizing trabecular tumor (HTT) of the thyroid. Additionally, our novel finding of GLIS3 expression via immunohistochemistry enhances diagnostic precision for these tumors. Notably, our series demonstrates the correlation between positive GLIS3 expression and detection of PAX8::GLIS3 fusion by RNA sequencing, potentially expediting HTT diagnosis.