Related Experiment Video
Updated: Jan 14, 2026
Detection of Extravascular Trypanosoma Parasites by Fine Needle Aspiration
Published on: August 7, 2019
"Atypical" cells in fine-needle aspiration biopsy specimens of benign thyroid cysts
William C Faquin1, Edmund S Cibas, Andrew A Renshaw
1Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. WFaquin@Partners.org
Insights
Atypical cells in thyroid cysts are often benign cyst-lining cells, not malignant neoplasms. Recognizing their specific features can prevent unnecessary surgeries for thyroid nodules.
Area of Science:
- Endocrinology
- Cytopathology
- Surgical Pathology
Background:
- Thyroid cysts are common, with most benign nodules showing degenerative changes.
- Atypical cells in fine-needle aspiration biopsy (FNAB) specimens can raise concern for malignancy.
- Microscopic features of benign cyst-lining cells with atypical features are not well-described.
Purpose of the Study:
- To describe the cytologic and histologic features of benign thyroid cyst-lining cells with atypical features.
- To improve recognition of these benign cells to avoid unnecessary surgical intervention.
Main Methods:
- Reviewed 75 FNAB specimens from thyroid cysts with atypical cells and subsequent benign histologic correlation.
- Correlated cytologic, histologic, and immunohistochemical features.
- Compared findings with 12 FNAB specimens of cystic papillary carcinoma.
Main Results:
- Most atypical thyroid cysts (94%) were benign, though 29% could not exclude neoplasm.
- Atypical cells often resembled reparative epithelial cells with distinct borders, nuclear grooves, and spindled morphology.
- Cystic papillary carcinomas showed nuclear crowding and papillary architecture, lacking spindled morphology.
Conclusions:
- Atypical cyst-lining cells possess characteristic features (distinct borders, elongated shape, eosinophilic cytoplasm, distinct nucleoli) differentiating them from malignancy.
- Absence of nuclear crowding, pseudoinclusions, and papillary architecture supports benign diagnosis.
- Recommend reporting these cells as 'consistent with benign cyst lining cells'.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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".
