Clear cell follicular tumors

Thyroid tumors are rarely composed of over 50% of clear cells. There are several causes for cytoplasmic clearing, including accumulation of vesicles derived from dilated mitochondria, the accumulation of glycogen, mucin or deposition of intracytoplasmic thyroglobulin. Lipid deposition in clear cell follicular tumors is exceedingly rare: three cases of adenomas,, and three cases of carcinomas have been reported., In all of the clear cell thyroid tumors, one can find tumor cells with part clear/part non-clear cytoplasm in the process of transformation from regular cytoplasm to clear cytoplasm. In Hürthle cell tumors, the mitochondria become dilated and form numerous vesicles and the cytoplasm transforms from granular to clear., Vesicle formation is also found in clear cell follicular tumors. Clear cell follicular tumors with a signet-ring or lipoblast-like appearance are attributed to cytoplasmic thyroglobulin deposition: as Carcangiu et al. stated in 1985, “The natural history of thyroid tumors containing clear cells is more dependent on their basic cytoarchitectural features than on the presence, amount, or type of clear cells, and we suggest for these tumors to be evaluated for carcinoma by using standard morphologic criteria for their respective types.” This is still true today. Clear cell Hürthle cell tumors resemble clear cell renal cell carcinoma because both tumors have round nuclei and prominent nucleoli, which can lead to a diagnostic dilemma at times. On can resort to immunohistochemistry in difficult cases. Thyroglobulin and CD10 would be helpful.

The author encountered one case of clear cell follicular adenoma (Fig. 9.1) and three cases of clear cell follicular carcinoma. One was minimally invasive without angioinvasion from a 38-year-old woman with a 4.3 cm hypervascular solid nodule (Fig. 9.2). Two were minimally invasive follicular carcinoma with angioinvasion. The one from a 38-year-old man with a 4.5 cm nodule had thyroidectomy and electron microscopic study in another institution which showed vesicles from dilated mitochondria were the cause of clear cytoplasmic change. The cytology and histology are shown in Fig. 9.3.