Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites

Metastatic neuroendocrine neoplasms can have similar histologic appearances, and without an obvious primary, it may be difficult to determine the site of origin of the metastasis. Thyroid transcription factor-1 (TTF-1) is a nuclear protein expressed during the development of thyroid, lung, and forebrain. The clinical utility of TTF-1 to distinguishing between metastatic pulmonary and nonpulmonary well-differentiated neuroendocrine tumors (WDNET) has not been previously studied. One hundred fifty-eight primary and metastatic WDNET were evaluated for TTF-1 expression. The tumors included 20 pulmonary WDNET, including 17 typical and 3 atypical carcinoid tumors, 10 metastatic pulmonary WDNET, 26 intestinal WDNET, 24 metastatic intestinal WDNET, 3 thymic mediastinal WDNET, 30 thyroid tumors (10 medullary carcinomas, 5 follicular carcinomas, 5 follicular adenomas, 5 papillary carcinomas, and 5 anaplastic carcinomas), 10 parathyroid adenomas, 20 pituitary adenomas, 10 pancreatic WDNET, and 5 pheochromocytomas. TTF-1 expression was found in 19 of 20 (95%) pulmonary WDNET, 8 of 10 (80%) metastatic pulmonary WDNET, and in 0 of 50 (0%) intestinal WDNET. All thyroid tumors were diffusely positive for TTF-1, except for three anaplastic carcinomas. All parathyroid and pituitary adenomas, pancreatic and thymic WDNET, and pheochromocytomas were uniformly negative for TTF-1. These results indicate that TTF-1 is clinically useful in distinguishing metastatic pulmonary from metastatic WDNET of extrapulmonary origin.