Clinicopathological studies of esophageal carcinoma in achalasia: analyses of carcinogenesis using histological and immunohistochemical procedures.

Achalasia of the esophagus is a benign disease caused by dyskinesia of the lower esophagus and cardia and is presumed to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. We analyzed six surgically or endoscopically resected carcinomas among 54 cases of esophageal achalasia using histological and immunohistochemical procedures. The mean interval between the diagnosis of achalasia and carcinoma was 21.5 years. Four of the six cases were superficial early-stage cancers whilst the other two were advanced cancers invading the adventitia. Histological mapping of the resected esophageal specimens demonstrated marked hyperplastic changes of stratified squamous epithelium and multiple foci of dysplastic changes. The squamous cell carcinomas showed well-differentiated type with low-grade atypia, closely associated with dysplastic foci. Immunohistochemical staining for p53, p21, p16 and epidermal growth factor receptor suggested that the dysplastic epithelium was a borderline lesion between hyperplasia and in situ carcinoma. Our observations suggested that esophageal food stasis induces chronic hyperplastic esophagitis and eventually malignant transformation of esophageal epithelial cells, associated with dysplasia-carcinoma sequence.