Case study of elevated alpha-fetoprotein secondary to drug-induced hepatitis mimicking germ cell tumor: a diagnostic...

Alpha-fetoprotein (AFP) is a tumor marker commonly associated with hepatocellular carcinoma and germ cell tumors. However, non-malignant conditions, such as drug-induced liver injury (DILI), can also cause significant AFP elevation, leading to potential diagnostic confusion. We present a case highlighting this important diagnostic pitfall.

A 30-year-old female presented with respiratory symptoms and right-sided pleural effusion. In a high tuberculosis prevalence setting, she was empirically started on anti-tubercular therapy (ATT) for presumed pleural tuberculosis. Two weeks later, she developed clinical and biochemical features of hepatitis, accompanied by moderately elevated AFP (481 IU/mL; ~400 ng/mL). Imaging revealed a right upper lobe mass with mediastinal involvement, raising suspicion for a germ cell tumor. Causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 8, suggesting probable DILI. Histopathological examination with immunohistochemistry demonstrated positivity for TTF-1 and Napsin A and negativity for SALL4, confirming metastatic pulmonary adenocarcinoma and excluding a germ cell tumor. Serial monitoring showed normalization of AFP levels with resolution of hepatitis prior to the initiation of chemotherapy.

Moderate AFP elevation (~50-fold) is more consistent with hepatic regeneration in DILI than with AFP-secreting malignancies, which typically produce markedly higher levels. The temporal association between hepatitis resolution and AFP normalization supports a non-malignant cause.

AFP elevation should be interpreted in the clinical context, considering its magnitude and temporal trends. DILI is an important differential diagnosis. Histopathological confirmation is essential to avoid misdiagnosis and inappropriate management.