Zolbetuximab-related gastritis: a case report of the patient with prolonged gastrointestinal symptoms

Abstract

A 73-year-old male patient presented with anemia and was diagnosed with unresectable advanced gastric cancer with distant lymph node metastases. The biopsy specimen showed a poorly differentiated adenocarcinoma. Immunohistochemistry was negative for human epidermal growth factor receptor 2, positive for claudin- 18, and revealed a preserved mismatch repair status. A regimen of capecitabine, oxaliplatin, and zolbetuximab was chosen as the primary chemotherapy regimen. On day 2, the patient started complaining of nausea and decreased appetite, and his symptoms gradually worsened. Esophagogastroduodenoscopy performed on day 11 revealed an erythematous and edematous mucosa with white secretions throughout the stomach. A histopathological examination revealed epithalaxia at the surface and severe inflammatory cell infiltration in the lamina propria. These endoscopic and histological findings indicated zolbetuximab-related gastritis. His symptoms improved three weeks after the discontinuation of chemotherapy. Endoscopic and pathological improvements of the gastritis were confirmed three months after the discontinuation of zolbetuximab. This report describes the first case of prolonged severe gastrointestinal symptoms with severe gastritis caused by zolbetuximab, as demonstrated by endoscopic and histopathological evidence.

Keywords: Gastric cancer; Gastritis; Zolbetuximab.

Fig. 1

The endoscopic findings before and after the administration of zolbetuximab. Pretreatment (A, B), 11 days after administration (C, D) and 3 months after the discontinuation of zolbetuximab (E, F). A semi-circumferential Type 2 tumor (A) is shown in the lesser curvature of the gastric corpus against a background of atrophic gastric mucosa (B). The gastric carcinoma shrunk (C), and an erythematous and edematous mucosa with white secretions was observed throughout the whole stomach (D). Remarkable tumor shrinkage is evident (E), and inflammatory changes improved throughout the stomach (F)

Fig. 2

Histopathological findings at the tumor sites. A The histological type of the tumor is poorly differentiated carcinoma (H&E, × 100). B Tumor cells are claudin 18-positive (> 75%). Used antibody was VENTANA OptiView CLDN18 (43-14A; Roche Diagnostics, Tokyo, Japan) (×100)

Fig. 3

Pre-treatment histopathological findings of non-tumor sites in the stomach. A, B corpus; C, D antrum. A Biopsy specimen of non-tumor sites in the gastric corpus shows mild atrophic gastritis with mild inflammatory cell infiltration and a preserved glandular duct structure (H&E, ×100). B Gastric foveolar epithelia and glandular cells are claudin 18-positive (×100). Claudin18 antibody (34H14L15; abcam, Cambridge, UK) was used for the immunohistochemistry. C Non-tumor sites in the antrum show mild gastritis with inflammatory cell infiltration (H&E, ×100). D Gastric epithelial cells are claudin 18-positive (×100)

Fig. 4

Clinical course and serum albumin level of the patient. Gastrointestinal symptom including nausea, decreased appetite, and heartburn developed on day 2, gradually worsened over time, and continued for more than a month. EGD: esophagogastroduodenoscopy, GI: gastrointestinal, CAPOX: capecitabine + oxaliplatin, SOX: tegafur gimeracil oteracil potassium + oxaliplatin

Fig. 5

Histopathological findings of zolbetuximab-related gastritis in non-tumor site of the stomach. A–D corpus; E–H antrum. A Biopsy specimens of the inflammatory lesions in the gastric corpus show erosion at the surface and severe diverse inflammatory cell infiltration in the lamina propria (H&E, ×100). B Gastric epithelial cells are specifically claudin 18-positive (×100). Claudin-18 antibody (34H14L15; abcam, Cambridge, UK) was used for the immunohistochemistry. C Apoptosis of foveolar epithelium is indicated by yellow arrows (H&E, ×200). D Glandular atrophy and dropout are observed (H&E, ×200). E Biopsy specimens of the non-inflammatory sites in the gastric antrum show epithalaxia with severe inflammatory cell infiltration (H&E, ×100). F Remained glandular cells are stained with the claudin 18 antibody (×100). CD4 lymphocytes (G) and CD8 lymphocytes (H) are diffusely observed in the inflammatory lesions (×100). Immune subtype markers, including CD4 (1F6; Leica Microsystems, Wetzlar, Germany) and CD8 (C8/144B; Agilent Technology, Santa Cruz, CA, USA) were used for immunohistochemistry