Track

Case Reports

Abstract

Thyroid transcription factor-1 (TTF-1) is a protein that regulates gene production in thyroid and lung tissue. TTF-1 expression was originally restricted to thyroid and lung carcinomas; however, expression has been reported in other organs. More specifically, TTF-1 immunostaining can help distinguish lung from breast carcinoma as both are classically CK7 positive and CK20 negative. However, markers consistent with breast origin, like ER and mammaglobin, have also been reported in lung cancers. Furthermore, TTF-1 expression has also been observed in cases of breast carcinoma. Herein, we present a 64-year-old female with a 1.6 x 1.4 cm indurated plaque on the left medial areola. Diagnostic mammography was unremarkable, and ultrasound displayed an isoechoic intradermal solid mass. A punch biopsy demonstrated infiltrating tumor cells within the dermis without epidermal involvement. Immunostaining revealed diffuse CK7 positivity and focal EMA expression, consistent with ductal formation. S100 highlighted small dermal nerve bundles, in close approximation to tumor foci. CK5/6 and CK20 were both negative. TTF-1 was positive (clone SPT24); however, repeat staining with a more specific TTF-1 antibody (8G7G3/1 clone) demonstrated only focal, weak reactivity. Additionally, there was diffuse expression of GATA3 and TRPS1, focal mammaglobin reactivity, and rare BRST-2 expression. Napsin-A was negative. Prognostic biomarkers showed strong ER positivity and PR negativity with minimal HER2 reactivity. The immunophenotypic findings confirmed a diagnosis of breast carcinoma. We aim to raise awareness regarding the utility and limitations of TTF-1, differing antibody clone specificities, and potential diagnostic pitfalls when determining primary site of origin.