Gastric cancer is a large public health problem, worldwide, with 951,000 new cases diagnosed in 2012. This represents 6.8% of all newly diagnosed tumor cases. 723,000 people died from gastric cancer in 2012, accounting for 8.8% of all tumor-caused deaths. Although, the incidence of gastric cancer has decreased in recent years, the incidence of indolent cell carcinoma has increased, especially in Asia, the United States, and Europe, accounting for 35-45% of gastric adenocarcinomas. From 1970 to 2000, the incidence rate increased 10-fold. The increase in the proportion of Indolent cell carcinoma in gastric adenocarcinoma may be due to a change in pathological staging according to the characteristics of these tumors. Since 1990, when the WHO published the gastric cancer staging, Indolent cell carcinoma has become a specific tissue staging that is easily identified in gastric cancer. Previously, Indolent cell carcinoma was classified as “diffuse” according to Lauren’s staging, “invasive” according to Ming staging, and “undifferentiated” according to Nakamura staging. It is classified as “undifferentiated” according to Nakamura typing, and “advanced (high-grade)” according to UICC typing. At present, indolent cell carcinoma is a poorly adherent tumor consisting of tumor cells with mucin in the cytoplasm and a crescent-shaped eccentric nucleus according to the WHO staging. Not all “undifferentiated” or “diffuse” gastric cancers are indolent cell carcinomas. Although Indolent cell carcinoma is considered “leathery stomach” based on histologic staging, it is distinct from “leathery stomach”, which is defined by macroscopic thickening and hardening of the gastric wall The “leather stomach” is defined macroscopically as a thickening and hardening of the stomach lining, secondary to an interfibrillary reaction. Therefore, 10%-20% of “leathery stomach” is not caused by IPC. Epidemiologic features of Indocellular carcinoma The incidence of gastric adenocarcinoma is decreasing since the advent of Helicobacter eradication. However, the incidence of RBC cancer is increasing, accounting for 8-30% of gastric cancers. The epidemiologic features and risk factors of indolent cell carcinoma are very different from those of other types of gastric adenocarcinoma. Indolent cell carcinoma is more common in women than non-Indolent cell carcinoma, with a sex ratio of approximately 1, compared to less than 1/2 for gastric adenocarcinoma. patients with Indolent cell carcinoma are younger, 7 years earlier than non-Indolent cell carcinoma, with a mean age of 55-61 years. The ethnic distribution is unclear. A recent study of 10,000 gastric cancer patients found that Indian-ring cell carcinoma was more common in blacks, Asians/Pacific Islanders, American Indians/Alaskans, and Hispanics. Asians, in particular, accounted for 14% of the patients, but this study had a lower incidence of Indian-ring cell carcinoma in Asians than has been reported in other literature. The incidence of indolent cell carcinoma is approximately 30%. In contrast, studies in Asian countries have shown that the incidence of indolent cell carcinoma is 15% in Korea, 10% in Japan, and 6-15% in China. There is a clear clinical difference between indolent cell carcinoma and non-indolent cell carcinoma Based on clinical features, indolent cell carcinoma is more common in the middle stomach than non-indolent cell carcinoma. Indolent cell carcinoma is generally advanced, stage 4, T3/T4 and N2. In contrast, some other literature reports that ring cell carcinoma is more common in early gastric cancer. In fact, early stage and late stage indolent cell carcinoma represent two different subtypes. In advanced gastric cancer, peritoneal spread is the most common metastatic area and some authors recommend laparoscopic evaluation prior to treatment. Indolent cell carcinoma-specific oncogenic pathways Indolent cell carcinoma has specific oncogenes, unlike tubular gastric adenocarcinoma. There are two main pathological processes at the cellular level, the absence of cell adhesion molecules and the accumulation of mucins in large vesicles. E-calmucin, encoded by the CDH1 gene, is a cell-to-cell adhesion molecule that plays an important role in tumor formation. In indolent cell carcinoma, it may be involved in the early process of tumor formation. A large proportion of cases of indolent cell carcinoma found that deletion of E-calmodulin caused oncogene activation, and in addition, the expression of CDH1 and some other adhesion molecules can downregulate many of the upstream proteins of the pathway. PI3K may be associated with oncogene activation in indolent cell carcinoma. Activation of the ErbB2/ErbB3 complex in combination with PI3K leads to phosphorylation of tyrosine sites and activation of downstream signals, including p38 MAPK. p38MAPK activation results in a lack of cell-cell association by disrupting adhesion junctions. Treatment of indolent cell carcinoma i. Endoscopic resection ii. Chemotherapy A study 20 years ago found a remission rate of 16% for indolent cell carcinoma compared to 65% for non-indolent cell carcinoma. However, for metastatic indolent cell carcinoma, paclitaxel analogs may be more effective. The authors found that the remission rate of docetaxel combined with 5FU and oxaliplatin was greater than 65% for indolent cell carcinoma and almost comparable to that of non-indolent cell carcinoma. III. Targeted therapy In the REGARADS trial, a phase III clinical study of ramolutumab, ramolutumab significantly improved overall survival time in previously treated gastric cancer. In subgroup analysis, ramolutumab had better efficacy for diffuse gastric cancer, but not intestinal gastric cancer (HR=0.56;95% CI:0.36-0.85), suggesting that diffuse gastric cancer has a higher sensitivity to anti-angiogenic drugs. IV. Immunotherapy Finally, 23% of indolent cell carcinomas highly express PDL1; therefore, anti-PDL1 drugs are potentially a promising therapeutic agent for gastric cancer.