Primary Gastric Adenocarcinoma with Thyroid Transcription Factor-1 Positivity Mimicking Gastric Metastasis from Lung...

Thyroid transcription factor-1 (TTF-1) is a well-established immunohistochemical marker for tumors of lung and thyroid origin. Metastatic adenocarcinomas are often tested for TTF-1 expression to identify their primary site. Herein, we report a rare case of TTF-1-positive primary gastric adenocarcinoma that was initially misdiagnosed and treated as postoperative gastric metastasis from primary lung cancer.

A 58-year-old man underwent thoracoscopic right upper lobectomy with systemic lymph node dissection for lung cancer of the right upper lobe. The pathological diagnosis was invasive adenocarcinoma (pT2bN0M0, Stage IIA). He received 3 courses of postoperative adjuvant platinum doublet chemotherapy. One year and 2 months after surgery, he was diagnosed with gastric and adrenal tumors. Immunohistochemical analysis of the gastric lesion demonstrated TTF-1 positivity, leading to the diagnosis of gastric and adrenal metastatic recurrence of lung cancer. The patient received triple therapy with carboplatin, pemetrexed, and pembrolizumab, followed by maintenance therapy with pemetrexed and pembrolizumab. During treatment, the adrenal metastasis achieved a complete response; however, the gastric lesion showed gradual progression on endoscopic follow-up. As primary gastric cancer could not be ruled out, the patient underwent robot-assisted distal gastrectomy with D2 lymph node dissection and Billroth I reconstruction, 3 years and 4 months following lung resection. Immunohistochemical staining of the gastric tumor revealed adenocarcinoma that was positive for TTF-1 and caudal-related homeodomain protein 2 (CDX2) and negative for napsin A. In contrast, lung cancer tissue was weakly positive for TTF-1 and negative for napsin A and CDX2. Based on the immunohistochemical staining and histological findings, the final diagnosis was primary gastric adenocarcinoma. The postoperative course was uneventful, and maintenance chemotherapy with pemetrexed and pembrolizumab was resumed. Four years and 10 months after cancer surgery, the patient remains in complete response.

This case highlights the diagnostic challenge posed by TTF-1-positive gastric tumors, which may be mistaken for metastatic lesions from lung cancer. As TTF-1 expression is not entirely specific to tissues of lung or thyroid origin, diagnosis should be based on a comprehensive evaluation of morphological and immunohistochemical findings, together with clinical information, including treatment response and disease course.