Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon

Summary Metastatic papillary thyroid carcinoma without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon. We retrieved seven of such cases and described in details the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n = 3), lateral (n = 3), or both neck compartments (n = 1). The histotype of the metastatic disease was papillary thyroid carcinoma (PTC, n = 5), poorly differentiated thyroid carcinoma (PDTC) in association with a PTC columnar variant (n = 1), and anaplastic thyroid carcinoma (ATC) in association with a PTC tall cell variant (n = 1). Fibrosis was present in the thyroid of five patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with PDTC did not recur and died of unknown causes. Finally, the patient with ATC was alive with distant metastasis at last follow up. The median follow up for this cohort was 2.2 years (range 0.8–17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAFV600E positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases.