The extremely rare occurrence of invasive squamous cell carcinoma arising from normal epithelial lining of a thyroglossal duct remnant cyst is documented by demonstrating the histopathologic transition from normal squamous epithelium to squamous cell carcinoma. The requirements that must be fulfilled to accept a lesion as arising de novo from the epithelial lining are outlined, and all requirements are achieved. The lesion is differentiated from the less rare papillary or papillary-follicular adenocarcinoma of residual thyroid tissue of the thyroglossal duct tract remnants.
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