Squamous esophageal histology and subsequent risk of squamous cell carcinoma of the esophagus. A prospective follow-up study from Linxian,China.Cancer.1994Sep15;74(6):1686-92.

BACKGROUND. Linxian, China, has some of the highest rates of esophageal cancer in the world. Previous authors have proposed that esophagitis, atrophy, and dysplasia may be precursor lesions of esophageal cancer in such high risk populations. METHODS. To examine the relationship between squamous esophageal histology and subsequent esophageal cancer in Linxian, the authors prospectively followed 682 participants of a 1987 endoscopic survey for 3.5 years and compared their initial biopsy diagnoses with the occurrence of squamous cell carcinoma during this follow-up period. RESULTS. Squamous cell carcinoma of the esophagus was identified in 52 (7.6%) of the participants during the follow-up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for squamous cell carcinoma incidence by initial histologic diagnoses were as follows: normal, 1.0 (reference); basal cell hyperplasia, 2.1 (0.4-9.8); mild dysplasia, 2.2 (0.7-7.5); moderate dysplasia, 15.8 (5.9-42.2); severe dysplasia, 72.6 (29.8-176.9); dysplasia not otherwise specified, 22.9 (6.7-78.0); and carcinoma in situ, 62.5 (24.1-161.9). CONCLUSION. In this study, moderate dysplasia, severe dysplasia, and carcinoma in situ were the only histologic lesions associated with a significantly increased risk of developing squamous cell carcinoma of the esophagus within 3.5 years after endoscopy. Increasing grades of dysplasia were associated with increasing risk, but severe dysplasia were associated with increasing risk, but severe dysplasia and carcinoma in situ had similar degrees of risk, findings that suggest a continuous spectrum of esophageal intraepithelial neoplasia, without morphologically distinguishable dysplasia and in situ carcinoma. A longer follow-up will be necessary to fully evaluate the less severe diagnostic categories, which may take more than 3.5 years to affect the occurrence of squamous cell carcinoma in this high risk population.

Histological classification of intraepithelial neoplasias and microinvasive squamous carcinoma of the esophagus.Am J Surg Pathol. 1989 Aug;13(8):685-90.

We reviewed a total of 119 resected esophagi with intraepithelial neoplasias of low grade (including slight or moderate dysplasias), high grade (including severe dysplasia and carcinoma in situ), or microinvasive squamous carcinoma (i.e., not invasive beyond the submucosa and without metastases in regional lymph nodes). Epithelial buds bulging into the stroma were noted in noninvasive intraepithelial lesions. The most severe degree of histological alteration was used to characterize each case. Of the 119 cases, five were low-grade, 38 were high-grade, and the remaining 76 specimens contained microinvasive squamous carcinoma. Of these, 23 invaded only the lamina propria. Nine invaded the muscularis mucosae, 16 invaded the inner half of the submucosa, and the remaining 28 invaded the outer half of the submucosa. Epithelial buds were divided according to their configuration into types I, II, and III. Grade I was characterized by regular epithelial buds of the same size, grade II had regular buds that varied in size, and grade III had irregular buds (i.e., buds of varying length and width with irregular contours). Our study of 66 specimens with microinvasive squamous carcinoma showed that one of the two specimens that had low grade dysplasia also had type III buds, while 56 of the remaining 64 (87.7%) with high grade dysplasia also had type III buds. Microinvasion originated at the tip of the type III epithelial buds in 12 specimens. Similar results have been demonstrated in experimental animals. We conclude that in the esophageal mucosa, there is a close relationship among the degree of squamous cellular atypia, the formation of epithelial buds, and the progression toward invasive carcinoma.