Cytomorphologic and Molecular Features of Hyalinizing Trabecular Tumor of Thyroid: Smears and ThinPrep

Summary: Introduction: Hyalinizing trabecular tumors (HTTs) are rare low risk thyroid follicular neoplasms characterized by a trabecular growth pattern and nuclear pseudoinclusions that are challenging for diagnosis on cytology due to their overlapping morphologic features with papillary thyroid carcinoma (PTC), especially on ThinPrep stain. This study aimed to analyze the cytomorphological features with conventional smears and ThinPrep preparation. Materials and Methods: HTT confirmed by surgical resections or molecular study during the past 15 years were found from our institutional database search. The corresponding fine needle aspiration (FNA) reports prior to the resection were reviewed. The cytology slides of three cases were able to be retrieved and reviewed to evaluate the cytomorphologic features. Results: The patients (n = 8) were averagely 59 years old with female predominance to male (7:1). Mean size of the nodules is 1.96 ±0.84 cm (Table 1). The most common thyroid Bethesda category (TBS) of the HTT nodules were TBS III (3/8) followed by TBS V (2/8, Table 1). Molecular studies were performed on 3 cases with one nodule showing PAX8::GLIS3 fusion, a pathognomonic genetic alteration of HTT. On cytology, the most characteristic features include round to elongated nuclei, cytoplasmic tail, nuclear pseudoinclusions and hyaline stroma (Table 2 and Figure 1). Conclusions: Accurate diagnosis of HTT by FNA is challenging due to overlapping cytomorphological features with PTC especially that nuclear pseudoinclusions are also features of HTT. Well-circumscribed nodule on radiology, the presence of spindle cells with long cytoplasmic tails, hyaline material, and absence of nuclear clearing are clues for HTT. ThinPrep preparation makes the diagnosis more difficult due to infrequent nuclear pseudoinclusions and lack of hyaline stroma. Identifying PAX8::GLIS3 fusion by molecular studies can aid in the diagnosis. In summary, a comprehensive approach incorporating cytomorphological, radiological, and molecular findings is necessary to accurately diagnose HTT and avoid unnecessary total thyroidectomy.