Simultaneous Occurrence of Papillary Thyroid Carcinoma and Medullary Thyroid Carcinoma: A Systematic Review

Background/Objectives: The concurrent occurrence of papillary (PTC) and medullary (MTC) thyroid carcinoma within the same thyroid gland is an exceptionally rare clinical entity. We conducted a systematic review to synthesize available evidence on the clinicopathological features, diagnostic pathways, and therapeutic outcomes of patients presenting with simultaneous PTC and MTC. Methods: This systematic review was conducted in accordance with PRISMA guidelines and was registered in PROSPERO. Comprehensive electronic searches across PubMed, MEDLINE, EMBASE, Scopus, and Web of Science were performed up to January 2025. Original clinical cohorts reporting on synchronous PTC and MTC (sample size ≥10) were included, while single-case reports and small series (n < 10) were excluded. Study quality was evaluated using the Newcastle–Ottawa Scale (NOS), and a narrative synthesis was performed. Results: Eight studies comprising 462 patients met the inclusion criteria. Over 70% of patients had preoperative cytological suspicion or biochemical evidence (elevated calcitonin) of MTC, whereas synchronous preoperative identification of both malignancies occurred in only 24% of cases. Among patients with available histological subtype data, 61% (148/243) presented with true collision tumors separated by normal thyroid parenchyma, whereas 39% (95/243) exhibited mixed medullary–follicular thyroid carcinoma (MMFTC) morphology. Primary MTC lesions were generally larger than the concurrent PTCs. Overall lymph node metastasis was reported in 44% of evaluated patients (predominantly MTC-derived), and distant metastasis occurred in 8%. Conclusions: Simultaneous PTC and MTC are predominantly characterized by an incidental PTC microcarcinoma alongside a larger MTC component that dictates disease staging and nodal dissemination. Further prospective studies and basic research are required to fully understand the potential shared pathophysiological mechanisms and the behavior of these coexisting tumors.