The optically clear nucleus. A reliable sign of papillary carcinoma of the thyroid?

The clear ('Orphan Annie Eye') nucleus has been accepted as one of the important microscopic features of papillary carcinoma of the thyroid. This study undertook an examination of 100 consecutive thyroid lesions exclusive of papillary, mixed, and follicular carcinomas for the presence of these nuclei. Only two lesions (2%), a follicular adenoma and diffuse hyperplasia, had such nuclear morphology but as focal changes. Thirty-seven cases of papillary, mixed, and follicular carcinoma were also studied. Clear or empty nuclei were present in 83% of papillary carcinomas. One carcinoma of follicular type had clear nuclei in a diffuse distribution. 'Pseudoclear' nuclei were noted in a variety of situations ranging from normal thyroids to diffuse hyperplasia, where they were present in 65% of cases. We conclude that clear nuclei when present as a diffuse change in a thyroid tumor are a reliable sign of papillary carcinoma, but are not pathognomonic. If the character of the clear nuclei is questionable, other histologic features of papillary carcinomas should be looked for, such as papillae with overlapping nuclei, psammoma bodies, and multifocality. It was also found that frozen sections and imprints do not demonstrate the nuclei; they appear only in fixed tissues.