Search

Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes.Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty.Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p0.001, p0.001, p = 0.005).Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.

BACKGROUND& AIMS: Lymphocytic esophagitis is ill defined and lymphocyte-rich inflammatory lesions of esophageal squamous epithelium are believed to show non-specific histological changes. This study was performed to investigate the histological and molecular criteria in lymphocytic esophagitis. METHODS: We collected 33 biopsies from 28 patients with lymphocytic esophagitis, which were diagnosed between 2010 and 2012 (17 men and 11 women, mean age = 60,8 and 61,1 years, respectively). Grading was performed by the number of lymphocytes (50/HPF cut off value) and according to Purdy et al. The inflammatory infiltrate was characterized by using the XTRACT robot (STRATIFYER, Cologne, Germany), quantitative real-time-PCR (FOXP3, CXCL9, CXCL13, IGHM, CD3, CD4 and CD8) and immunohistochemistry (CD4, CD8, TIA, GranzymB and Caspase 3). Spearman rank test was used to calculate the correlation between these parameters. RESULTS: Apoptoses could be detected in 83% of severe cases (15/18) and in 47% of mild cases (7/15) without differences between the two grading systems. High levels of cytotoxic T-cells were present in 80% of severe cases with apoptoses (12/15) and in 5 cases without visible apoptoses in H&E stain, mostly mild cases. The overall number of lymphocytes correlated with the number of apoptoses (p = 0,002) and the number of CD8 positive lymphocytes (p = 0,005). Cases with apoptoses showed high levels of CD8 positive lymphocytes. A positive correlation between spongiosis and levels of cytotoxic T-cells could be demonstrated (p = ,0,0001). Evaluation of clinical data revealed a correlation between high levels of cytotoxic lymphocytes and a wavey mucosal surface (p = 0,025), reddening of esophageal epithelium (p = 0,017) and a stipplelike exsudate (p = 0,015). Within the group with apoptoses a strong correlation between cytotoxic T-cells (= CD8) and regulatory T-cells (= FOXP3) (p = ,0,0001) was found. Expression of CXCL9 correlated with the expression of CD4 and CD8 (p = 0,05 and p = 0,0042, respectively). CONCLUSIONS: Our data suggest that the term "lymphocytic esophagitis" should only be used as an umbrella-term in several diseases and therefore we suggest "lymphocyte-rich esophagitis" to be used for further subdivisions. Two different subgroups of this lymphocyte-rich variant of chronic esophagitis can be distinguished: Lymphocyte-rich esophagitis with apoptosis (LEA) and lymphocytic esophagitis with no apoptosis (LENA). Apoptotic keratinocytes are usefull in grading LEA, as they can be found in large numbers predominantely in severe forms. The number and localization of apoptoses distinguishes esophageal Crohn's disease and lichen planus from LEA. Further studies should focus on the question, whether our findings are a hint to an autoimmunologic mechanism or not.