Rare Metastases of Well-Differentiated Thyroid Cancers: A Systematic Review

A minority of metastatic well-differentiated thyroid cancer (WDTC) patients present with end-organ disease other than in the lung, bone or lymph nodes. These metastases tend to be overlooked because of their low incidence, and this results in delayed diagnosis. The purpose of this study was to perform a systematic review of the clinical and histologic features of unusual WDTC metastases. A systematic literature search of bibliographic databases, reference lists of articles, and conference proceedings was performed up to 2013. Studies were included if they reported on adult patients with WDTC and pathology-proven metastases to end-organs other than lung, bone, or lymph nodes. A total of 238 studies were included in a qualitative analysis. Data is expressed as N (%) and median [interquartile range]. A total of 492 patients (median age, 62 years [50-70 years]) were identified in 197 case reports and 42 case series. There were 22 different end-organ metastatic sites documented with either papillary [255 (57 %)], follicular [172 (39 %)], or Hurthle-cell [18 (4 %)] histology. A total of 181 (41 %) patients presented with solitary metastasis and 54 (93 %) with elevated serum thyroglobulin. Positron emission tomography and whole-body radioactive iodine scans revealed hypermetabolic foci in 28 (97 %) and 50 (81 %) cases, respectively. Disease-free interval following the initial diagnosis of the primary thyroid cancer was highly variable, ranging from synchronous presentation [66 (33 %)] to metachronous disease after 516 months [mean 86 months (SD 90)]. WDTC can manifest with highly variable and unusual clinical features. Rare sites of metastases should be considered in the absence of the more common extra-cervical disease recurrence locations.