Mucoepidermoid carcinoma of the thyroid gland: genetic insights and a rare clinical presentation.

Mucoepidermoid carcinoma (MEC) of the thyroid gland (TMEC) is exceptionally rare, with poorly understood histogenesis and molecular characteristics. This report describes a unique case of incidentally detected TMEC, accompanied by a comprehensive molecular characterization. A 60-year-old woman, during follow-up for diffuse large B-cell lymphoma, was detected to have a metabolically active lesion involving the thyroid gland. Resection revealed an infiltrative tumor composed of squamoid cells with focal gland formation and intracytoplasmic lumina. An adjoining focus of the infiltrative follicular subtype of papillary thyroid carcinoma (PTC) was also noted. Immunopositivity for CK19, p63, PAX8, and thyroglobulin and negativity for CD10 confirmed the diagnosis of mucoepidermoid carcinoma associated with PTC. MAML2 fusion was absent. Next-generation sequencing (NGS) revealed pathogenic/likely pathogenic variants involving genes previously documented in PTC. Post-recovery, the patient developed a third malignancy, squamous cell carcinoma involving the esophagus. The case has an unusual presentation, occurring in conjunction with two other metachronous malignancies. Co-existent PTC, immunopositivity for thyroid-differentiation markers, and the genetic profile confirm a squamoglandular metaplasia of follicular cells as the origin. The absence of MAML2 fusion questions its WHO categorization as a "salivary gland-type carcinoma." Detailed molecular profiling, while contributing to a better understanding of the pathogenesis of this enigmatic neoplasm, also helped decipher potentially actionable genetic variants.