Supplementary Material for: Peritoneal carcinomatosis with gray-to-black-colored peritoneum and intestines treated with nivolumab, a case report

Introduction: Peritoneal carcinomatosis of unknown primary is a life-threatening condition that presents diagnostic and therapeutic challenges with poor prognosis. In 2021, nivolumab was approved for carcinoma of unknown primary in Japan.
Case Presentation: A 70-year-old male underwent first-line nivolumab treatment for peritoneal carcinomatosis of unknown primary, in accordance with the patient's wishes. Four months after initiating treatment, he developed immune-related adverse event (irAE) hepatitis, which responded to methylprednisolone; however, the patient died a few days later. Autopsy revealed an uncommon presentation of thick, firm, gray peritoneum with globally gray-to-black ischemic intestines, massive adhesions, ascites, and disseminated peritoneal nodules. No evidence of superior mesenteric artery (SMA) occlusion, segmental necrosis, or typical features of ischemic colitis or nonocclusive mesenteric ischemia (NOMI) was evident. Histological findings revealed fibrous thickening of the peritoneum. Pathological examination collectively suggested that the primary site of the peritoneal carcinomatosis was the non-mucinous adenocarcinoma, not otherwise specified (NOS) and mucinous adenocarcinoma of the appendix, which had not been detected on imaging or endoscopy. The final staging was pT4b, pN1a, pM1c, pStage IVC based on the TNM Classification (8th edition).
Conclusion: Although irAE colitis is well documented, peritoneal complications associated with immune checkpoint blockades (ICBs) have been scarcely reported in the literature, especially gray-colored peritoneum as in this case. The etiology is still unclear, but might collectively involve inflammation, stromal fibrosis, microscopic tumor invasion, and metabolic dysregulation in the tissue/tumor microenvironment. The unusual peritoneal presentation warrants further case accumulation and investigation into its pathogenesis to improve clinical management strategies.