Context: The immunohistochemical identification of thyroid transcription factor-1 (TTF-1) is regarded as the presence of a nuclear pattern of staining and is used to identify tumors of thyroid or pulmonary origin. Although there have been reports of cytoplasmic expression of TTF-1, the significance of this pattern has not been studied in detail.

Objectives: To determine the incidence at which cytoplasmic immunostaining for TTF-1 occurs and to analyze the diagnostic value of this pattern of immunoreactivity.

Design: Histologic sections of 361 consecutive cases of neoplasms stained for TTF-1 were reviewed, and those showing cytoplasmic staining in the tumor cells or in nonneoplastic cells were selected. Clinical correlation was obtained on the latter cases regarding the origin of the tumor.

Setting: An immunohistochemistry laboratory in a tertiary-care institution.

Results: The 361 tumors were obtained from 29 organ sites and corresponded to primary and metastatic neoplasms. Twenty-three (6.3%) tumors showed cytoplasmic staining for TTF-1. In 13 of these, the primary site of origin was established with certainty: 7 were lung carcinomas (3 primary lung adenocarcinomas, 1 primary large cell carcinoma, 1 metastatic small cell carcinoma to the liver, 1 metastatic adenocarcinoma to a neck lymph node, and 1 metastatic adenocarcinoma to thigh soft tissue), 3 colonic adenocarcinomas (2 metastases to vertebrae and 1 to lung), 1 metastatic breast ductal adenocarcinoma to femur, 1 metastatic laryngeal squamous cell carcinoma to liver, and 1 meningioma involving the orbit bone. There were 3 lung carcinomas with concomitant nuclear immunostaining. Nonneoplastic liver tissue was the most frequent nontumoral tissue in which the cytoplasm stained with TTF-1 antibody.

Conclusion: Occasional cytoplasmic staining for TTF-1 in tumors is seen, but it is a nonspecific finding; when present, it should be disregarded for diagnostic purposes.