Squamous Cells in Thyroid Cytology and Their Clinical Significance: A Multi‐Institutional Study

ABSTRACT Background Squamous cells are uncommon in thyroid fine needle aspirations (FNAs) presenting diagnostic challenges. We report our multi‐institutional experience. Materials and Method The electronic data were searched for thyroid FNAs containing squamous cells at the Johns Hopkins Medicine, New York University Langone Hospital, United States, and Fimlab Laboratories, Finland (2001–2023). The patients' demographics, clinical history, and pathologic diagnosis were recorded. Results One hundred and seven cases (103 patients) were identified 35 males and 68 females (median age 58 years). Forty‐eight cases (44.9%) were malignant, primary carcinomas with squamous features, such as anaplastic thyroid carcinoma (ATC), and metastatic or directly invasive squamous cell carcinomas (SqCC) including oral, oropharyngeal (HPV‐related), esophageal, and laryngeal SqCC. Twenty‐seven cases (25.2%) contained benign squamous cells with cystic background, suggestive of developmental cysts. Nineteen cases (17.8%) contained metaplastic benign squamous cells within an adenomatoid nodule. Seven cases (6.5%) contained atypical squamous cells. Four cases (3.7%) showed squamous cells with bacterial or fungal organisms, suggestive of esophageal fistula/diverticulum, and two cases (1.9%) contained benign squamous cells with unknown source. Thirty‐six cases had surgical follow‐up, 33 (91.7%) were concordant (23 metastatic or directly invasive SqCC, 8 undifferentiated/ATC, and 10 papillary thyroid carcinoma). Ancillary studies were used confirming HPV‐related SqCC, or therapeutic targets (BRAF V600E), with highly variable staining in ATC. Conclusion Squamous cells in thyroid FNAs carry a broad differential diagnosis with variable prognoses. It is crucial to interpret squamous cells in the context of clinical and radiographic findings for optimal patient care.