Paradoxical Pyogenic Granuloma Associated With Ramucirumab but Not Bevacizumab: A Case Suggesting Differential Effects of <scp>VEGF</scp> Receptor and Ligand Inhibition

Pyogenic granuloma is a benign vascular lesion that may bleed repeatedly and impair daily activities. Although ramucirumab is an anti-angiogenic agent, paradoxical pyogenic granuloma has rarely been reported during its use. We describe a 75-year-old man with advanced lung adenocarcinoma who developed multiple bleeding pyogenic granulomas during docetaxel plus ramucirumab therapy. Histopathology confirmed lobular capillary proliferation consistent with pyogenic granuloma. Because the lesions repeatedly bled and reduced quality of life, they were excised and ramucirumab was discontinued. The patient was subsequently treated with docetaxel plus bevacizumab, and no recurrence or worsening of pyogenic granuloma was observed. This intra-patient contrast suggests that VEGFR-2 blockade and VEGF ligand inhibition may have different effects on paradoxical vascular proliferative lesions. Clinicians should recognize this rare toxicity and consider switching anti-angiogenic strategy in selected cases.