title: Histopathologic patterns among achalasia subtypes.
abstract: BACKGROUND
  Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns.
  
  
  METHODS
  We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by two expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes.
  
  
  RESULTS
  Manometry studies were categorized as follows: type I (n = 20), type II (n = 20), type III (n = 3), and esophagogastric junction outflow obstruction (EGJOO) (n = 3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs 13/20, p = 0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p = 0.016). CD3(+) /CD8(+) cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO).
  
  
  CONCLUSIONS
  The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings - from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology - emphasizes that 'achalasia' represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.
authors.affiliation: Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Sodikoff
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Lo
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Shetuni
authors.affiliation: Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Kahrilas
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Pandolfino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004931:Esophageal Achalasia / Q000145:classification / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D049630:Esophageal Sphincter, Lower / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D004943:Esophagogastric Junction / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D004947:Esophagus / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005355:Fibrosis; D005724:Ganglia / Q000166:cytology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009133:Muscular Atrophy / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D055815:Young Adult
keywords: achalasia; esophagus; histopathology; immunohistochemistry; motility