Search

Introduction: Mesenchymal tumors of the thyroid gland are extremely rare. We report the cytomorphologic characteristics of 12 mesenchymal tumors occurring in the thyroid gland and highlight the diagnostic difficulties encountered in their cytologic evaluation., Materials and Methods: The cytopathology and surgical pathology archives from 5 large institutions were searched for thyroid mesenchymal tumors that had an FNA available for review. Clinicopathologic and cytomorphologic characteristics for each case were evaluated., Results: Twelve cases of mesenchymal tumors occurring in the thyroid were identified in our search. Patient age ranged from 28 to 84 years (median, 60 years). The cases occurred in 7 women and 5 men. The tumor size ranged from 1.4 to 14 cm (median, 3.3 cm). The tumors were as follows: hemangioma (n = 4; 33.3%), angiosarcoma (n = 2; 16.7%), schwannoma (n = 2; 16.7%), solitary fibrous tumor (n = 2, 16.7%), metastatic synovial sarcoma (n = 1, 8.3%) and metastatic pleomorphic rhabdomyosarcoma (n = 1, 8.3%). The cytomorphologic features of the tumors were similar to those of their counterparts occurring in different sites. An accurate diagnosis was achieved in six primary thyroid mesenchymal cases (60%). Five patients (41.7%) underwent total thyroidectomy, and 3 patients received partial thyroidectomy (25%). Three patients (25%) did not receive a thyroidectomy and subsequent surgical information was not available in 1 case (8.3%)., Conclusions: Mesenchymal tumors of the thyroid are extremely uncommon. Cytologic diagnosis of these tumors is often challenging due to the morphologic overlap with diverse epithelial and non-epithelial thyroid lesions. Ancillary studies such as immunohistochemistry and molecular studies are essential for accurate diagnosis., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Previous in vitro and in vivo toxicological studies on the effects of yessotoxin (YTX) on E-cadherin have provided conflicting results with regard to alterations of its turnover. We have then studied the effects of YTX on the degradation pathway of E-cadherin in intact cells under controlled conditions, and found that the 100kDa E-cadherin fragment (ECRA100) accumulated in cells exposed to YTX is an intermediate degradation product, detectable when the process is altered by agents interfering with endocytosis and lysosomal functioning. Cell treatment with YTX slows down the degradation of ECRA100, without affecting the half-lives of intact E-cadherin and its associated proteins beta-catenin and gamma-catenin. When cells have been treated with an inhibitor of proteasomes (lactacystin), the accumulation of ECRA100 induced by YTX was reduced. Accumulation of ECRA100, in turn, was observed after cells were exposed to inhibitors of lysosomal functioning (chloroquine) and of clathrin-mediated endocytosis (chloropromazine), but not to agents interfering with the caveolae-mediated pathway (nystatin and filipin III). The actin cytoskeleton was involved in endocytosis of ECRA100, because its accumulation was detected after MCF-7 cells had been treated with cytochalasin D. Nocodazole treatment of MCF-7 cells, in turn, did not lead to detection of ECRA100, indicating that microtubules should not be involved in its degradation. We have concluded that YTX interferes with the degradation pathway of E-cadherin by slowing down the endocytosis and complete disposal of the ECRA100 intermediate proteolytic fragment, whose cell levels are consequently increased in cells exposed to the toxin. These findings reconcile the apparent contradictions of previous studies, showing that YTX does not promote E-cadherin degradation per se, but interferes with its complete disposal.

YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA(90)), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA(90), as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo.