Variations in inflammation and nerve fiber loss reflect different subsets of achalasia patients

Background. Achalasia is a debilitating motility disorder with an unknown etiology. Past research has demonstrated a spectrum of histological findings. The objective of this study was to further characterize the histopathology of achalasia, with attention to subsets of findings that may exist, possibly reflecting different pathogeneses. Materials and methods. Lower esophageal muscle was obtained during surgery for achalasia (n = 12) or cancer (n = 9). Immunohistochemistry was performed to identify various inflammatory cells and nerve fibers, and grading was done by an expert pathologist. Clinical data were taken from medical records. Results. There were two subsets of achalasia specimens with different histological findings. Group A (7/ 12; 58%) had an inflammatory infiltrate in the myenteric plexus consisting primarily of T-lymphocytes. Group B (5/12; 42%) had no such infiltrate and had less myenteric plexus macrophages versus Group A (P = 0.03). The loss of nerve fibers was most evident in the muscularis propria in achalasia as compared to controls (P = 0.01), and this loss was more striking in Group B versus A (P = 0.04). The mean duration of symptoms was 16.6 (A) versus 6.4 years (B) (P = NS). Conclusions. Two subsets of achalasia patients exist with different histological findings. Group A had T-cell-rich inflammation present with associated macrophages. Group B, with no inflammation, had greater loss of nerve fibers in the muscularis propria versus Group A, and therefore, may represent more aggressive disease with shorter duration of symptoms. These results suggest that various pathogeneses of achalasia may exist that share a common pathway of aganglionosis.