Question

Which tumor is positive for TTF-1?

• A. Sq (Squamous cell carcinoma)
• B. Small (Small cell carcinoma)
• C. Adeno Ca (Adenocarcinoma)
• D. Carcinoid

Hint:

TTF-1 marks thyroid and lung type-II pneumocyte lineage — think which lung cancer forms glands and is the classic positive.

Answer 1

The Correct Option is C

Step 1: What is TTF-1? Thyroid Transcription Factor-1 (TTF-1, also called NKX2-1) is a nuclear transcription factor normally expressed in thyroid follicular cells and in lung type-II pneumocytes / Clara cells. As an immunohistochemical marker it stains tumours arising from these tissues.

Step 2: Apply to lung cancers. Among primary lung carcinomas, TTF-1 is characteristically positive in pulmonary adenocarcinoma (and also in small cell carcinoma). It is most useful, however, as the marker that distinguishes a lung-origin adenocarcinoma from squamous cell carcinoma and from metastases. The accompanying histology image of glandular/acinar tumour tissue is consistent with adenocarcinoma.

Step 3: Choose the answer. Of the listed options the classic TTF-1-positive tumour is adenocarcinoma - Option C.

Step 4: Why the others are less correct. (A) Squamous cell carcinoma is TTF-1 NEGATIVE and instead expresses p40 / p63 / CK5/6. (B) Small cell carcinoma can be TTF-1 positive, but it is neuroendocrine and not the answer the stem (with adenocarcinoma morphology) is pointing to. (D) Carcinoid (well-differentiated neuroendocrine tumour) is typically TTF-1 negative or only weakly positive and is identified by chromogranin/synaptophysin. Hence adenocarcinoma is the best single answer.

Final Answer: Option C - Adenocarcinoma.