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Background: Clear cell carcinoma in the thyroid gland is rare. It is important to distinguish primary thyroid clear cell carcinoma from metastases, since its clinical behaviors and treatment options were different. Clinical Case: A 47-year-old woman without past medical history presented to our outpatient surgery department with right neck mass for 8 months. Thyroid ultrasonography revealed a 3.9 cm nodule in the right thyroid. Thyroid function test was within the normal range. Fine needle aspiration cytology of the nodule showed suspicious for neoplasm. She underwent radical total thyroidectomy and lymph node dissection. Pathology revealed an unusual carcinoma comprising cuboidal cells with irregular nuclear contours, some eosinophilic or clear cytoplasm, arranged in infiltrating nests or cords with marked stromal hyalinization, highly suggestive of a clear cell carcinoma. Ectopic thymic tissue was present adjacent to the tumor. By immunohistochemical (IHC) staining, tumor cells were p63 (+), TTF-1 (-), thyroglobulin (-), PAX8 (-), synaptophysin (-), CD5 (-), and CD117 (-). Tumor genetic sequencing detected EWSR1-CREM fusion genes. For disease extent evaluation, two out of seven lymph nodes obtained during operation were positive of tumor metastases. Whole body computed tomography (CT) 3 months after operation revealed no residual thyroid tissue, neck lymphadenopathies or intra-abdominal metastases. A pulmonary ground-glass opacities of 7mm in diameter was found, which was stationary at a repeated CT scan 6 months later. Clinical Lesson: Clear cell carcinoma in the thyroid gland could be primary, arising from clear cell change of follicular or papillary thyroid carcinoma. The negative IHC stain of thyroglobulin, TTF, PAX8, as well as lack of papillary or follicular architecture made primary thyroid clear cell carcinoma unlikely. Most of the metastatic clear cell carcinoma to the thyroid gland arose from renal primary. However, there was no clinical or radiographic evidence of renal tumor in our case. Although ectopic thymic tissue was identified on pathology, negative IHC staining of PAX8, CD5 and CD117 made thymic origin less likely. Positive IHC staining of p63 and a novel EWSR1-CREM fusion gene confirmed the diagnosis of salivary clear cell carcinoma. According to our literature review, there were only 3 cases of clear-cell carcinoma with EWSR1-CREM fusion gene (1), and our case is the first case who presented with clear cell carcinoma in the thyroid. In conclusion, the importance of IHC stain and molecular testing in determining the primary origin of clear cell carcinoma were addressed in our case. Reference: (1) Chapman E, et al. Am J Surg Pathol. 2018;42(9):1182-1189

SUN-480 An Unusual Clear Cell Carcinoma in the Thyroid. Where Is the Primary?