Similar to other head and neck organs, thyroid pathology encompasses a broad spectrum of diagnostic entities. The significant overlap in architectural or cytological features across these entities presents a unique set of diagnostic challenges. This review focuses on diagnostic pitfalls related to metastasis in thyroid pathology, with particular emphasis on morphologic assessment and differential diagnosis. Key scenarios discussed include (1) intranodal thyroid inclusions, which may closely mimic metastatic papillary thyroid carcinoma in cervical lymph nodes, and (2) metastatic tumors to the thyroid that can simulate primary thyroid neoplasms across the full histologic spectrum, from low-grade to high-grade malignancies, especially in the absence of a known concomitant primary malignancy or when the clinical history is not provided. Awareness that both benign thyroid tissue and metastatic tumors may exhibit atypical architectural or cytologic features is critical to avoiding overdiagnosis or misclassification. Rigorous morphological assessment remains the first step in the diagnostic workup. Immunohistochemistry serves as a valuable adjunct when used judiciously, particularly mutation-specific markers such as BRAF VE1 and lineage-associated markers including TTF-1, PAX8, and thyroglobulin, with careful consideration of their sensitivity and specificity. Integration of histologic findings with clinical history and radiologic information ultimately enables accurate distinction between metastatic and non-metastatic lesions in thyroid pathology.
Chuang et al. (Sat,) studied this question.