Routine morphometrical analysis can improve reproducibility of dysplasia grade in Barrett’s oesophagus surveillance biopsies

Background: The grade of dysplasia found in Barrett’s oesophagus surveillance biopsies is a major factor to determine follow up and treatment. However, it has been reported that the reproducibility of the grading system is not optimal. Aims: To compare routine and expert dysplasia grades in Barrett’s oesophagus surveillance biopsies. To evaluate prospectively morphometrical grading support and to assess the pitfalls in its daily application. Methods: Consecutive biopsies (n = 143) were graded routinely by experienced general surgical pathologists as no dysplasia (ND), indefinite for dysplasia, low grade dysplasia (LGD), and high grade dysplasia (HGD). Two expert gastrointestinal pathologists blindly reviewed all sections. The stratification index of nuclei, mean nuclear area, and Ki67area% were assessed routinely according to a strict protocol. With these features, the previously described morphometrical grade was calculated for each case. The grades provided by the experts, surgical pathologists, and morphometry were compared. Results: The general pathologists graded many more cases as dysplastic than did the experts. Complete agreement between the experts’ grades and the original grades was 50 of 143 (35%). Sixty four of the 71 original LGDs and 11 of the 23 original HGDs were downgraded by the experts, whereas one LGD was upgraded. In 93 of the 143 biopsies, at review pitfalls or special characteristics of a technical nature (tangential cutting, severe inflammation, ulcer or the squamocylindrical junction very close by, among others) were seen in the part of the biopsy marked as diagnostic. These probably contributed in part to the original overdiagnoses and could have been prevented or corrected. The morphometrical grading model has not been developed to compensate for this; application of the current morphometrical grading method is not allowed and may result in erroneous (usually too high) morphometrical grades. In spite of this, all HGDs according to the experts were recognised as such by morphometry, also in these technically less adequate sections or areas. However, 46% of the experts’ downgrades occurred in technically adequate sections and thus were caused by a difference in interpretation. Here, morphometrical support proved to be useful because, in agreement with the experts, it downgraded 51% of the original LGDs, upgraded one of eight NDs to LGD and one of 39 LGDs to HGD. Conclusions: Experts downgraded a high proportion of biopsies graded as LGDs and HGDs by the surgical pathologists. Morphometrical grading can be used for daily quality control; the results were close to those of the experts and corrected a large number of cases erroneously graded by surgical pathologists.

[1]  V. Álvarez,et al.  Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma. , 1997, Journal of clinical pathology.

[2]  G. Tytgat,et al.  Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma , 1998, Gut.

[3]  J K Greenson,et al.  Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. , 2001, Human pathology.

[4]  E. Montgomery,et al.  Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. , 2001, Human pathology.

[5]  G Van Belle,et al.  Observer variation in the diagnosis of dysplasia in Barrett's esophagus. , 1988, Human pathology.

[6]  P H Bartels,et al.  Knowledge-guided segmentation and morphometric analysis of colorectal dysplasia. , 1995, Analytical and quantitative cytology and histology.

[7]  J. V. van Lanschot,et al.  Clinical decision making in Barrett's oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation , 1998, The Journal of pathology.

[8]  R. Goyal,et al.  The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. , 1996, Gastroenterology.

[9]  L. Jarvis,et al.  Morphometric analysis of gastric dysplasia , 1985, The Journal of pathology.

[10]  P. Barbini,et al.  Gastric dysplasia: A stereological and morphometrical assessment , 1987, The Journal of pathology.