Extreme CYFRA 21-1 Elevation in Lung Adenocarcinoma is Uncommon: Evidence of Tumor Burden Over Histological Specificity

Abstract

Serum tumor markers are commonly used in lung cancer management, but interpretation may be difficult when levels are markedly elevated and discordant with histopathological findings. CYFRA 21-1 is typically associated with squamous cell carcinoma, whereas CEA is more characteristic of adenocarcinoma. We report a 43-year-old man presenting with generalized weakness, severe back pain, and inability to walk. Magnetic resonance imaging revealed a thoracic mass and extensive vertebral lytic-blastic lesions suggestive of disseminated skeletal metastases. Histopathology confirmed metastatic adenocarcinoma. Immunohistochemistry showed CK7 and TTF-1 positivity with CK20 negativity, supporting a diagnosis of lung adenocarcinoma. Serum markers showed markedly elevated CEA (>1000 ng/mL) and extremely high CYFRA 21-1 (>500 ng/mL), exceeding levels commonly reported in adenocarcinoma. The unusually high CYFRA 21-1 may reflect extensive tumor burden, diffuse bone metastases, and increased tumor cell turnover rather than histological subtype alone. This case highlights the importance of integrating tumor markers with radiological, histopathological, and immunohistochemical findings in advanced lung cancer.