title: Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios.
abstract: BACKGROUND
  Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard.
  
  
  OBJECTIVE
  We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis.
  
  
  METHODS
  We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A.
  
  
  RESULTS
  Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results.
  
  
  CONCLUSIONS
  Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University , Rome , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Picarelli
authors.forename: Raffaele
authors.initials: R
authors.lastname: Borghini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Donato
authors.forename: Marco
authors.initials: M
authors.lastname: Di Tola
authors.forename: Cristina
authors.initials: C
authors.lastname: Boccabella
authors.forename: Claudia
authors.initials: C
authors.lastname: Isonne
authors.forename: Marco
authors.initials: M
authors.lastname: Giordano
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Cioccio
authors.forename: Adriana
authors.initials: A
authors.lastname: Marcheggiano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Antonio
authors.initials: A
authors.lastname: Tiberti
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002446:Celiac Disease / Q000175:diagnosis*; D003937:Diagnosis, Differential; D004386:Duodenum / Q000473:pathology*; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D009924:Organ Culture Techniques; D015203:Reproducibility of Results; D055815:Young Adult
keywords: celiac disease; histology; in vitro; organ culture; serology