Abstract
INTRODUCTION: Lung adenocarcinoma, the most common subtype of non-small cell lung cancer (NSCLC), is typically characterized by positive immunohistochemical (IHC) staining for thyroid transcription factor-1 (TTF-1) and Napsin A. However, a small subset of these tumors is negative for both markers, posing a significant diagnostic challenge and carrying distinct prognostic implications. Renal metastases from lung cancer are uncommon and are rarely detected at initial diagnosis. CASE PRESENTATION: We report the case of a 42-year-old male who presented with nonspecific constitutional symptoms of diffuse pain and weight loss. Comprehensive imaging revealed a large primary mediastinal mass with extensive stage IVB metastatic disease involving the bilateral adrenal glands, bones, iliac lymph nodes, and bilateral kidneys. A CT-guided biopsy of the mediastinal mass confirmed a poorly differentiated invasive adenocarcinoma. The tumor's immunoprofile was notably negative for both TTF-1 and Napsin A, but positive for cytokeratin 7, necessitating a broad IHC workup to exclude other primary sites. The patient was initiated on palliative chemotherapy with carboplatin and paclitaxel, demonstrating a significant clinical and partial radiological response. CONCLUSION: This case highlights the clinical and pathological features of a TTF-1-/Napsin A-negative lung adenocarcinoma. It underscores the systematic diagnostic workup required to confirm a lung primary in this challenging context, illustrates the correlation between this specific tumor phenotype and its aggressive clinical behavior with widespread metastases, and emphasizes the central role of comprehensive biomarker testing in the modern management of advanced NSCLC.