Soshi Oyama, Shuhei Suzuki, Takanobu Kabasawa, Takumi Kanauchi, Shotaro Akiba
Background and Clinical Significance: Zolbetuximab, a claudin 18.2-targeted monoclonal antibody, has demonstrated efficacy in advanced gastric cancer. Hypoalbuminemia has emerged as a notable adverse effect, but its underlying mechanism remains unclear. Case Presentation: A 53-year-old male with unresectable advanced gastric cancer received zolbetuximab-based combination therapy, achieving tumor regression enabling conversion surgery. During six cycles of treatment, serum albumin levels decreased from 4.3 g/dL to 3.5-3.6 g/dL (grade 1 hypoalbuminemia). A histopathological examination of the surgical specimen revealed hypertrophic gastritis characterized by marked foveolar hyperplasia, increased mucus secretion, and pyloric gland metaplasia on the lesser curvature. These findings suggest that zolbetuximab-induced mucosal alterations may contribute to hypoalbuminemia through enhanced protein loss. Conclusions: This is the first pathological documentation of hypertrophic gastritis associated with zolbetuximab therapy. Clinicians should monitor albumin levels during treatment and consider nutritional support when indicated. These findings provide important insights for optimizing patient management and ensuring safe conversion surgery planning.