Thyroglobulin Measurement in Fine Needle Aspirates (Tg-FNA) of Cystic Neck Masses for Detection of Papillary Thyroid Carcinoma (PTC)

Introduction: Nuclear pseudoinclusions are one of the most specific pathologic features in diagnosing papillary thyroid carcinoma (PTC). However, the biologic nature of these pseudo-inclusions is largely unknown. Beta-catenin is an oncoprotein involved in Wnt signaling pathway which is activated in several malignancies including PTC. Using immunohistochemistry, we studied the expression of beta-catenin in PTC and hyalinizing trabecular adenoma (HTA), with particular focus on its expression in pseudoinclusions, both on histologic sections and on cytologic specimens. Materials and Methods: A cohort of 13 cases, including 8 cases of PTC and 5 cases of HTA, was applied in this study. Beta-catenin immunohistochemitry was performed on histology block recuts and cytology slides of each case. The beta-catenin labeling index of pseudoinclusions was counted in 15 high power fields and calculated in comparison with those counted on immediate next H&E stained histologic slides. Cytology slides were digitally scanned before destaining and restaining with beta-catenin. The number of beta-catenin-labeled pseudo-inclusions was compared with those digitally scanned slides. Results: On histologic sections, neoplastic cells from both PTC and HTA show much stronger membranous staining pattern of beta-catenin, compared to adjacent normal follicles or colloid nodules. However, labeling index of beta-catenin for nuclear pseudo-inclusions is significantly different between PTC and HTA. Strong intranuclear staining of beta-catenin was seen in 93.5% (range of 72-100%) of the pseudoinclusions in PTC, while only 6.4% (range of 0-13%) of pseudo-inclusions in HTA showed positive staining pattern (p<0.001). For cytologic slides, although it demonstrated similarly strong membranous staining pattern for beta-catenin in PTC cells, none of the nuclear pseudo-inclusions in both PTC and HTA was labeled with beta-catenin antibody on cytologic smears. Conclusions: Overexpression of the beta-catenin oncoprotein was seen in majority of the nuclear pseudo-inclusions in PTC, but only rarely seen in HTA. This differential expression suggests that activation of the betacatenin is likely involved in the formation of “malignant peudoinclusions” in PTC, but not in “benign peudoinclusions” in HTA. The failure of betacatenin labeling of pseudoinclusions on cytologic slides may be in part attributed to inability of the antibody to penetrate into nucleus through the intact cell membranes in cytologic preparations.