The significance of "indefinite for dysplasia" grading in Barrett metaplasia.

CONTEXT: For a confident diagnosis of dysplasia in Barrett metaplasia, the epithelial atypia should also involve the surface epithelium. However, pathologists are often faced with biopsies where the crypts show dysplasia, but the surface epithelium is either uninvolved or unevaluable. We previously grouped these cases with indefinite for dysplasia (IND). OBJECTIVE: To determine the clinical significance of IND grading in Barrett metaplasia. DESIGN: All biopsies from 276 prospectively followed patients with Barrett metaplasia, who did not have high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) on initial biopsy, were graded as negative for dysplasia, IND, low-grade dysplasia (LGD), HGD, and EAC. Biopsies with multifocal IND or LGD were graded as INDM or LGDM, respectively. RESULTS: Only 3 of 193 patients (2%) with an initial diagnosis of negative for dysplasia and only 1 of 48 patients (2%) diagnosed with IND progressed to HGD or EAC. By contrast, 1 of 7 patients (14%) with INDM, 2 of 21 (10%) with LGD, and 1 of 7 (14%) with LGDM progressed to HGD or EAC. There was no significant difference in progression rate between patients with an initial diagnosis of negative for dysplasia and those diagnosed IND nor were there significant differences among patients with initial diagnoses of INDM, LGD, or LGDM. Kaplan-Meier analysis showed that patients with INDM, LGD, or LGDM on initial biopsy (group 1) were more likely to progress to HGD or EAC than were those patients who were diagnosed negative for dysplasia or IND (group 2; log-rank test, P < .001). CONCLUSIONS: Multifocal IND in an esophageal biopsy from a patient with Barrett metaplasia has the same clinical implication as LGD.

Goblet cell mimickers in esophageal biopsies are not associated with an increased risk for dysplasia.

CONTEXT: Identification of intestinal-type goblet cells (ITGCs) in hematoxylin-eosin-stained sections of esophageal biopsies is essential for the diagnosis of Barrett metaplasia. However, we have seen cases diagnosed as Barrett metaplasia based solely on cells that pose morphologic similarity to ITGCs on hematoxylin-eosin staining or stain positive with Alcian blue. OBJECTIVE: To determine the clinical significance of goblet cell mimickers. DESIGN: Initial biopsies from 78 patients with original diagnosis of Barrett metaplasia negative for dysplasia and a mean follow-up of 72 months were reviewed and reclassified into 3 categories: (1) ITGCs, (2) goblet cell mimickers, or (3) neither. Sections from available paraffin blocks were stained with Alcian blue at pH 2.5. The presence of the different types of cells and positive Alcian blue staining were correlated with each other and evaluated for their significance as predictors of progression to dysplasia. RESULTS: Goblet cell mimickers were present in 35 cases and were associated with ITGCs in the same biopsy in 23 (66%) of these cases. Intestinal-type goblet cells were present in 56 cases, and the remaining 10 cases, although called Barrett on the original report, did not show either ITGCs or goblet cell mimickers. Only the presence of ITGCs was associated with significant risk for dysplasia (P = .008). Positive Alcian blue staining was not associated with a significant risk for dysplasia. CONCLUSIONS: Our results indicate that the diagnosis of Barrett metaplasia should be rendered with confidence only when ITGCs are identified on routine hematoxylin-eosin-stained sections.

Atypical NK-cell proliferation of the gastrointestinal tract in a patient with antigliadin antibodies but not celiac disease.

We describe a unique case of atypical natural killer (NK)-cell proliferation likely related to gluten sensitivity, mimicking NK-cell lymphoma. The patient, a 32-year-old man, has had persistent multiple erythematous bull-eye lesions in the stomach, small bowel, and large bowel for 3 years. Histologically, the lesions were well circumscribed and relatively superficial, composed of atypical medium-sized to large-sized lymphocytes with slightly irregular nuclear contours, a dispersed chromatin pattern, and clear cytoplasm. Immunohistochemistry and flow cytometry showed that the cells were NK cells expressing CD56 (aberrantly bright), T-cell intracellular antigen (TIA)-1, cytoplasmic CD3, and CD94, but not surface CD3, with bright aberrant expression of CD7 and a lack of other NK cell-associated markers. Polymerase chain reaction for rearrangement of the T-cell receptor-gamma chain gene showed no evidence of a clonal T-cell population, and in situ hybridization for Epstein-Barr virus encoded RNA was negative. There was no evidence of the involvement of peripheral blood or bone marrow. Although a diagnosis of extranodal NK/T-cell lymphoma was considered because of the atypical morphology and immunophenotypic aberrancy, no chemotherapy was given because of the relatively superficial nature of the infiltrates, lack of significant symptoms, and negativity for Epstein-Barr virus. Two years after initial presentation, the patient was found to have high titers of antigliadin antibodies with no other evidence of celiac disease. After instituting a gluten-free diet, many of the lesions regressed, suggesting that this atypical NK-cell proliferation may be driven by an anomalous immune response. Awareness of this case may prevent pathologists from misdiagnosing similar lesions as NK/T-cell lymphomas. It is as yet unknown whether this process occurs more commonly in patients with gluten sensitivity, or in other settings, and the pathogenesis is as yet undetermined.

Expression of the high mobility group proteins HMGI(Y) correlates with malignant progression in Barrett's metaplasia.

Expression of the high mobility group proteins HMGI(Y) has been shown to be a marker of malignancy in thyroid and pancreatic lesions and to correlate significantly with malignant progression in the colon. The aim of this study was to determine whether HMGI(Y) expression is associated with malignant progression in Barrett's metaplasia (BM). Immunoperoxidase staining for HMGI(Y) was performed on sections of formalin-fixed paraffin-embedded endoscopic esophageal biopsies from 42 patients with BM. These consisted of 19 biopsies negative for dysplasia (ND), 16 with low-grade dysplasia (LGD)/indeterminate for dysplasia (IND), and 7 with high-grade dysplasia (HGD)/adenocarcinoma (CA). The percentage of positive cells was recorded, and nuclear HMGI(Y) immunoreactivity in >10% of the cells was considered positive. Statistical analysis was performed using Fisher's exact test. Positive HMGI(Y) staining was detected in 2 of 19 (11%) cases ND, 5 of 16 (30%) LGD/IND cases, and 7 of 7 (100%) HGD/CA cases. Biopsies with HGD/CA were significantly more likely to be positive for HMGI(Y) than biopsies ND (P < 0.0001) or with LGD/IND (P = 0.0046). We conclude that HMGI(Y) expression is significantly associated with malignant progression in BM. Additional studies are needed to determine whether BM biopsies that are ND or LGD/IND and positive for HMGI(Y) are more likely to progress to adenocarcinoma.