Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population

Abstract

Background: Oesophageal squamous cell carcinoma (OSCC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment.

Aims: To identify the clinically relevant histological precursors of OSCC.

Subjects: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China.

Methods: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models.

Results: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 (reference), oesophagitis 0.8 (0.2-3.2), basal cell hyperplasia 1.9 (0.8-4.5), mild dysplasia 2.9 (1.6-5.2), moderate dysplasia 9.8 (5.3-18.3), severe dysplasia 28.3 (15.3-52.3), and carcinoma in situ 34.4 (16.6-71.4).

Conclusions: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk, indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease.

Figure 1

Histological categories. (A) Normal: basal zone thickness <15% of epithelial thickness; papillae limited to the lower two thirds of the epithelium; no atypia. (B) Oesophagitis: epithelium infiltrated by neutrophils and eosinophils. (C) Basal cell hyperplasia: basal zone thickness >15% of epithelial thickness; no atypia. (D) Mild dysplasia: atypical cells in the lower third of the epithelium. (E) Moderate dysplasia: atypical cells in the lower two thirds of the epithelium. (F) Severe dysplasia: atypical cells in all thirds of the epithelium but not full thickness. (G) Carcinoma in situ: full thickness involvement by atypical cells, without invasion. (H) Squamous cell carcinoma: early invasion into the lamina propria.

Figure 2

Cumulative incidence of oesophageal squamous cell carcinoma by initial histological diagnosis. BCH, basal cell hyperplasia; Mild dys, mild dysplasia; Moderate dys, moderate dysplasia; Severe dys, severe dysplasia; Dysplasia NOS, dysplasia not otherwise specified; CIS, carcinoma in situ.