"Atypical" cells in fine-needle aspiration biopsy specimens of benign thyroid cysts

Cystic lesions of the thyroid are common. Most are benign nodules with degenerative changes in a multinodular goiter. Fine-needle aspiration biopsy (FNAB) specimens from these cystic nodules usually are easily interpreted as benign. However, occasionally, cells with atypical features are encountered, increasing the possibility of a cystic malignant neoplasm. To the authors' knowledge, the microscopic features of these benign cells, presumed to be of cyst-lining origin, have not been well described to date. To refine the description of their morphologic features, with the belief that better recognition will avoid unnecessary surgery, the authors examined the cytologic and corresponding histologic features of thyroid cysts with "atypical" cells.

A total of 149 FNAB specimens from thyroid cysts containing atypical cells were identified. Seventy-five specimens with subsequent histologic correlation showing a benign cystic thyroid nodule were selected for study. The cytologic features of the atypical cyst-lining cells were reviewed and correlations were made with histologic, immunohistochemical, and clinical features. In addition, 12 FNAB specimens of histologically proven cystic papillary carcinoma diagnosed as atypical were reviewed for comparison.

The majority of specimens (94%) were diagnosed cytologically as atypical thyroid cysts. However, in 29% of these specimens, a papillary or Hurthle cell neoplasm could not be excluded. The cytologic features of the atypical cells most often resembled classic reparative epithelial cells consistent with a cyst-lining origin. The most common features were cohesive flat sheets (84%), distinct cell borders (96%), nuclear enlargement (92%), nuclear grooves (79%), dense granular cytoplasm (79%), small distinct nucleoli (85%), fine chromatin (87%), and elongate to spindled cytomorphology (57%). In contrast to the atypical cells from benign cysts, cystic papillary carcinomas lacked the repair-like spindled cytomorphology, and showed nuclear crowding (100%), as well as papillary microarchitecture (50%), and rare intranuclear pseudoinclusions (42%). Histologically, the atypical cells in aspirate specimens corresponded to cyst-lining cells, which exhibited a spectrum ranging from flattened elongate cells with eosinophilic cytoplasm to more polygonal cells with abundant eosinophilic cytoplasm, enlarged irregular nuclei with pale chromatin, prominent nuclear grooves, and distinct nucleoli. Immunohistochemical staining of a subset of the resected thyroid cysts showed that the cyst-lining cells were positive for keratin and thyroglobulin, consistent with thyroid follicular cells.

Atypical cyst-lining cells were found to have characteristic features (e.g., distinct cell borders, elongated shape, eosinophilic cytoplasm, and distinct nucleoli) and lacked nuclear crowding, intranuclear pseudoinclusions, and papillary architecture that, in many specimens, allowed them to be recognized as benign. The authors recommended that the subset of cells with the characteristic features described in the current study be reported as "consistent with benign cyst lining cells".