A Diagnostic Enigma: Hyalinizing Trabecular Tumor Masquerading as Malignancy in a Young Male

Background: Hyalinizing trabecular tumor (HTT) is a rare follicular-derived thyroid neoplasm that often mimics papillary and medullary thyroid carcinoma, leading to potential overtreatment. Case Presentation: A 25-year-old male presented with a painless midline thyroid swelling. Imaging revealed a cold nodule in the isthmus. Fine-needle aspiration cytology showed nuclear grooves, pseudoinclusions, and extracellular hyaline material, raising suspicion of malignancy. Hemithyroidectomy was performed due to indeterminate cytology. Histopathology demonstrated trabecular architecture with dense hyalinized stroma (PAS-positive, Congo red-negative), nuclear grooves, and absence of invasion. Immunohistochemistry showed thyroglobulin and TTF-1 positivity, with characteristic cytoplasmic/membranous Ki-67 (MIB-1) staining. Calcitonin and CEA were negative. NSE positivity was interpreted as nonspecific and used primarily to exclude medullary carcinoma. Results/Outcome: Final diagnosis of HTT was made. At 1-year follow-up, the patient remains disease-free with normal TSH levels and no evidence of recurrence on ultrasound.Conclusion: Recognition of the characteristic morphologic and immunohistochemical features of HTT is essential to avoid misdiagnosis and overtreatment. While PAX8::GLIS3 fusion is a molecular hallmark, diagnosis can be reliably established using morphology and immunohistochemistry where molecular testing is unavailable.