ArticleJournal of pathology and translational medicine2026
Hyalinizing trabecular tumors with areas resembling noninvasive follicular thyroid neoplasm with papillary-like nuclear features: an immunohistochemical and molecular analysis.
Article in Journal of pathology and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe coexistence of hyalinizing trabecular tumor (HTT) and areas with a morphology of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) within a single thyroid nodule has not been previously reported. We aimed to determine whether such tumors represent two independent neoplasms or a single tumor exhibiting divergent morphology.
methodsTen tumors containing both HTT and NIFTP-like areas were examined. The term "NIFTP-like" was used strictly as a descriptive morphological designation for areas that fulfill the histologic criteria of NIFTP. Immunohistochemical analyses of Ki-67 (MIB-1) and type IV collagen and targeted molecular testing were performed. Ten NIFTPs, 10 follicular adenomas, and three HTTs were used as controls.
resultsHTT components consistently showed characteristic membranous Ki-67 staining and intra-trabecular type IV collagen deposition, whereas NIFTP-like areas lacked these features, except for focal apical Ki-67 staining. Intranuclear cytoplasmic inclusions in HTT were positive for type IV collagen. NIFTPs showed neither membranous Ki-67 nor intra-trabecular type IV collagen. Molecular analysis demonstrated identical profiles between HTT components and NIFTP-like areas: three tumors harbored PAX8::GLIS3 fusions, and none showed RAS mutations. Pure HTT controls exhibited the same pattern.
conclusionsOur findings indicate that these follicular-patterned areas represent a morphological variant within the spectrum of HTT rather than a true NIFTP-related component or two separate neoplasms. These findings expand the recognized histologic diversity of HTT and highlight a potential diagnostic pitfall in follicular-patterned thyroid tumors. Focal apical Ki-67 staining may serve as a useful clue for distinguishing HTT from NIFTP.
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