In the clinic, we see many patients with their gastroscopy and pathology reports, looking at the reports that say: “chronic atrophic gastritis with mild or moderate low-grade intraepithelial neoplasia, or severe intraepithelial neoplasia”, “gastric adenomatous polyp with low-grade intraepithelial neoplasia “, or “colon adenoma with low-grade intraepithelial neoplasia” on the colonoscopy report. When the patient sees the word “neoplasia”, he/she becomes very nervous and seeks help from all levels of hospitals. Generally, the doctor will tell him/her, “This is a common pathological change, and modern medicine has found that this lesion is related to the development of cancer and can be regarded as a precancerous lesion of cancer.” When the patient hears “cancer”, he/she will be more afraid, nervous and anxious. So what is intraepithelial neoplasia? Is it really that scary? Today, I would like to take advantage of the holidays to give a brief introduction to intraepithelial neoplasia here, hoping to answer questions and solve problems. Gastric mucosal epithelial heterogeneous hyperplasia or atypical hyperplasia has been considered as the main precancerous lesion of gastric cancer because it is closely related to the occurrence of gastric cancer and is at the most important stage of the cancer process. It has long been highly valued by clinicians and pathologists. However, there is a lack of unified standard for the definition, classification, grading, histological criteria, regression and treatment plan of gastric mucosal epithelial hyperplasia at home and abroad, and the nomenclature is also confusing, therefore, it often causes inconsistency in diagnostic criteria and diagnostic terms applied by pathologists in judging gastric mucosal epithelial hyperplasia, heterogeneous hyperplasia and early gastric cancer, resulting in various problems such as patients’ confusion and physicians’ confusion. 1.What is heterogeneous hyperplasia? Heterogeneous hyperplasia, also known as atypical hyperplasia or atypical hyperplasia, and some call it interstitial change. Heterogeneous hyperplastic epithelium is defined as definite neoplastic non-invasive epithelium. Gastric mucosal epithelial heterogeneous hyperplasia and adenoma consist of heterogeneous proliferating epithelium. It is proposed that when the heterogeneous proliferating epithelium forms a flat lesion, the term gastric epithelial heterogeneous hyperplasia is applied; when the heterogeneous proliferating epithelium forms an elevated lesion, it is called “adenoma”; when the endoscopic lesion is not clearly distinguishable from the surrounding normal gastric mucosa and the histological manifestation is heterogeneous proliferating epithelium, the term gastric epithelial heterogeneous hyperplasia is also applied. 2.What is intraepithelial neoplasia? Intraepithelial neoplasia refers to a non-invasive neoplastic change in the epithelium above the basement membrane, which is a precancerous lesion, morphologically manifested by structural and cytological abnormalities. The lesion has a clonal transformation of genes and tends to develop into infiltration and metastasis. The term intraepithelial neoplasia is synonymous with heterogeneous hyperplasia and was first used by Richard in 1960 for precancerous changes in the squamous epithelium of the cervical mucosa, and its correct meaning is to emphasize that the essence of this precancerous lesion is the formation of an intraepithelial tumor. And this intraepithelial tumor formation contains a twofold meaning. In 2006, the World Health Organization proposed to replace anaplastic hyperplasia with intraepithelial neoplasia, which is divided into 2 grades, namely low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia, with low-grade intraepithelial neoplasia corresponding to mild and moderate anaplastic hyperplasia; and high-grade intraepithelial neoplasia corresponding to mild and moderate anaplastic hyperplasia. Low-grade intraepithelial neoplasia corresponds to mild and moderate anisotropic hyperplasia; high-grade intraepithelial neoplasia corresponds to severe anisotropic hyperplasia or carcinoma in situ. (1) What is low-grade intraepithelial neoplasia? What is the clinical significance? Low-grade mucosal intraepithelial neoplasia includes low-grade adenoma and low-grade intraepithelial neoplasia. In low-grade adenosarcoma, the glands are mildly crowded but fairly similar in size and shape, with pyknotic, regularly arranged basal nuclei and only mild to moderate nuclear deep staining. If the biopsy diagnosis is low-grade intraepithelial neoplasia, endoscopic treatment or follow-up is required. If gastro-oesophageal reflux is suspected to be basic, gastroscopic biopsy pathology is followed up after acid suppression therapy. In most patients, with therapeutic intervention, intraepithelial neoplasia can be eliminated or maintained. Some patients may progress to invasive love. Most lesions in the colon or rectum require endoscopic resection for treatment. (2) What is high-grade intraepithelial neoplasia? What is the clinical significance? High-grade intraepithelial neoplasia refers to mucosal changes with malignant cytologic and structural features, but without mesenchymal infiltration. High-grade intraepithelial neoplasia includes severe anaplastic hyperplasia and carcinoma in situ. Four diagnostic terms are included in this category, namely high-grade intraepithelial neoplasia, severe anisotropic hyperplasia, carcinoma in situ, suspicious invasive carcinoma, and intramucosal carcinoma. In the West, pathologists classify non-invasive lesions as high-grade intraepithelial neoplasia, whereas in Japan, pathologists mostly diagnose carcinoma. This shows that there are differences between Japanese and Western pathologists regarding the diagnosis of biopsy pathology. These issues are also currently a hot topic of international research in an attempt to find a common protocol. For high-grade intraepithelial neoplasia of the mucosa, the following protocols are recommended on a case-by-case basis: ① Most high-grade intraepithelial neoplasia of the mucosa can be treated locally by means of endoscopic treatment. ② The chance of lymph node metastasis from mucosal tumors of the esophagus, stomach, colon, and rectum is negligible. ③ The mortality rate of local resection is not significantly increased compared with esophage-lymph node resection. ④ Hypodifferentiated carcinoma within the gastric mucosa and lesions larger than 1 cm have increased lymph node metastasis and should be given surgical resection and lymph node dissection. Some studies found that the regression of intraepithelial neoplasia had 38-40% recovery of low-grade intraepithelial neoplasia, 89% could recover, 19-28% remained unchanged, and 0%-15% could progress to severe anaplastic hyperplasia or high-grade intraepithelial neoplasia. High-grade intraepithelial neoplasia can be recovered in 5% of patients, maintained in 14%, and progressed to cancer in 81%-85% of patients. For patients with clinical endoscopic pathology diagnosis of intraepithelial neoplasia, regular follow-up is crucial. With the development of endoscopic technology, it is of great clinical importance to detect early cancer for follow-up. In addition, the improvement of endoscopic treatment technology also provides patients with the opportunity for nonsurgical treatment. Western countries advocate that patients with moderate or low-grade anisocytic hyperplasia should be followed up closely endoscopically with an interval of 3 months in the first year of follow-up density, and 6 months when 2 follow-ups of endoscopic multi-point sampling are negative.