The diagnosis and management of ectopic thyroid cancer: a systematic review

Ectopic thyroid carcinoma (ETC) is a rare malignancy for which standardized treatment guidelines remain unavailable. This systematic review aimed to comprehensively characterize the clinical features, treatment patterns, outcomes, and prognostic factors of ETC using the largest case-based dataset reported to date.

A systematic literature search of PubMed, Scopus, and Web of Science was conducted from database inception to May 27, 2025. A total of 348 eligible reports were included. Data from 506 patients with ETC were extracted and analyzed, including demographics, tumor pathology, treatment strategies, recurrence, and survival outcomes.

The study included 506 patients, with a female-to-male ratio of 1.7:1 and a mean age of 41.6 years. Papillary thyroid carcinoma was the predominant histological subtype, accounting for 85.6% of cases. Most patients presented with localized disease (77.9%). Surgery was the primary treatment method (98.8%), and 40.6% of patients also received radioiodine therapy. Multivariable Cox regression showed that age >50 years (HR = 3.75, 95% CI: 1.92-7.32, P < 0.001) and ectopic tumor location in the chest, abdomen, or pelvis (HR = 7.23, 95% CI: 2.61-20.04, P < 0.001) were independently associated with worse overall survival. In the propensity-score-matched cohort, recurrence occurred in 3 of 50 patients who underwent orthotopic thyroidectomy and in 2 of 50 patients who did not, corresponding to recurrence rates of 6.0% and 4.0%, respectively. This difference was not statistically significant in paired analysis (McNemar P = 1.000).

This systematic review provides the largest synthesis of ETC cases to date and identifies advanced age and non-cervical ectopic tumor location as adverse prognostic factors. Orthotopic thyroidectomy was not associated with reduced recurrence after propensity-score matching. However, given the small number of recurrence events and the case-based nature of the available evidence, this finding should be interpreted as hypothesis-generating rather than definitive. These results support a risk-adapted management strategy in which thyroidectomy is individualized rather than performed routinely.

https://www.crd.york.ac.uk/prospero/, identifier CRD420250630606.