The Cytological, Clinical, and Pathological Features of the Cribriform-Morular Variant of Papillary Thyroid Carcinoma and Mutation Analysis of CTNNB1 and BRAF Genes

The cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is an unusual subtype of papillary thyroid carcinoma. The goal of this study was to determine the clinicopathological features of CMVPTC and whether the tumor can be diagnosed by fine-needle aspiration cytology.We retrospectively analyzed the clinical appearance and pathological findings in five patients with CMVPTC and sequenced exon 3 of CTNNB1 and exon 15 of BRAF in tumor tissue.All patients were young women, 15-34 years of age at the time of the cancer diagnosis. Preoperative cytological examination showed scattered tall columnar cells, fascicular spindle cells, and cribriform and morular patterns in the fine-needle aspirates of the thyroid from the five patients. Grossly, all tumors were well-circumscribed, solid or cystic. Immunohistochemically, most tumor cells showed nuclear expression of thyroid transcription factor-1, estrogen and progesterone receptors, and p53; cytoplasmic expression of cytokeratins 7 and 19, vimentin, and bcl-2; and cytoplasmic and nuclear accumulation of beta-catenin and galectin-3. There was no expression of thyroglobulin, cytokeratin 5/6, or human mesothelial cell-1. However, among these markers, the morular cells showed only positive immunostaining for beta-catenin, galectin-3, p53, and bcl-2. A CTNNB1 mutation was identified in only one case and no BRAF mutation was found in any of the five cases.Taken together, these data suggest that CMVPTC can be diagnosed preoperatively, based on careful cytology examination, and shows unique immunohistochemical findings.