Capillary Hemangioma of the Breast Parenchyma Mimicking New Primary Cancer or Metastasis During Ramucirumab Therapy for Advanced Gastric Cancer.

BACKGROUND/AIM: Ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), has been shown to prolong survival in patients with advanced gastric cancer when combined with paclitaxel as second-line chemotherapy in the RAINBOW study. The most common adverse events include hypertension, proteinuria, and hemorrhage, reflecting its anti-angiogenic activity. Although the VEGF signaling pathway is strongly implicated in the pathogenesis of hemangiomas, the development of new hemangiomas during VEGFR-2 inhibition is rarely reported. CASE REPORT: A 38-year-old woman with stage IV gastric adenocarcinoma presented with peritoneal dissemination and lymph node metastasis. She initially received FOLFOX plus immune checkpoint inhibitor therapy, achieving a partial response before disease progression. Second-line treatment with paclitaxel and ramucirumab was initiated. During therapy, chest computed tomography revealed a newly developed contrast-enhancing nodule in the left breast parenchyma, raising suspicion of metastasis or primary breast carcinoma. Breast ultrasonography confirmed a hypervascular lesion, and ultrasound-guided biopsy demonstrated numerous capillary-sized vessels lined by bland endothelial cells, consistent with capillary hemangioma. Owing to deterioration of her general condition, chemotherapy was temporarily discontinued. Despite subsequent third-line FOLFIRI and fourth-line trifluridine/tipiracil treatment, the patient eventually died of disease progression. Notably, follow-up chest CT scans showed gradual reduction and eventual spontaneous disappearance of the breast hemangioma, independent of systemic therapy. CONCLUSION: This is a rare case of a breast parenchymal capillary hemangioma arising during ramucirumab therapy for advanced gastric cancer, which regressed spontaneously. Clinicians should recognize that atypical vascular lesions may develop paradoxically during VEGFR-2 blockade and confirm histological diagnosis to avoid misinterpretation as metastasis or new primary malignancy.