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

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.
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