Follicular adenoma of the thyroid with hyalinizing trabecular tumor-like pattern

Hyalinizing trabecular tumor (HTT) is a rare and challenging, follicular cell-derived thyroid neoplasm characterized by a trabecular growth pattern, intratrabecular/intracellular basement membrane-like hyaline material, and nuclear pseudoinclusions. HTT is placed in the category of low-risk neoplasms in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumours, published in 2022. The diagnosis is supported by positivity for TTF1, Thyroglobulin and membranous MIB1 staining, and the specific GLIS gene rearrangements which have not been identified in other thyroid tumors. Follicular adenoma (FA) of the thyroid is known to display occasional or rare variant histology associated with diagnostic pitfalls. Herein, we describe three cases of FA showing a predominance of HTT-like pattern, leading to initial consideration of HTT, but lacking membranous MIB1 staining and GLIS fusions. Molecular profiling revealed PAX8::PPARG fusion in one case and none in the others. Distinguishing FA with HTT-like morphology from genuine HTT might have therapeutic and prognostic (follow-up) implications, based on the benign nature of the former and the low-risk biology of the latter. However, the full biological spectrum of this FA subtype and its genetic background need more delineation in larger future studies with long follow-up.