Hyalinizing trabecular tumor of the thyroid: A comprehensive review of clinicopathological features, diagnostic dilemmas, and emerging molecular insights.

Hyalinizing trabecular tumor (HTT), a rare thyroid neoplasm, is defined by its unique histopathological architecture and diagnostic complexity due to morphological mimicry of papillary thyroid carcinoma (PTC) and medullary thyroid carcinomas (MTC). This review consolidates contemporary insights into HTT's clinicopathological spectrum, diagnostic ambiguities, and molecular underpinnings. Epidemiologically, HTT predominantly affects middle-aged females, manifesting as circumscribed, asymptomatic nodules. Histologically, trabecular clusters of neoplastic cells embedded within hyalinized stroma are pathognomonic. The nuclear grooves and pseudoinclusions characteristic of HTT overlap with those of PTC, while amyloid-like deposits risk misclassification as MTC, necessitating comprehensive ancillary testing. Definitive diagnosis combines key tests: MIB1 membranous staining. BRAF V600E exclusion for PTC, and calcitonin negativity for MTC exclusion. Emerging molecular evidence reveals recurrent PAX8::GLIS3 fusions in >90 % of cases, suggesting diagnostic utility, though their prognostic relevance remains elusive. The most recent WHO classification categorizes HTT as a "low risk neoplasm" owing to the exceptionally low frequency with which it displays lymph node metastases, although debates persist regarding its intrinsic biological behavior. This review underscores the imperative for multidisciplinary collaboration to refine diagnostic accuracy, mitigate overtreatment, and advance targeted therapeutic strategies based on HTT's unique molecular profile.