Necrotizing sialometaplasia-like change of the esophageal submucosal glands is associated with Barrett's esophagus

Abstract

The esophageal submucosal glands (SMG) protect the squamous epithelium from insults such as gastroesophageal reflux disease by secreting mucins and bicarbonate. We have observed metaplastic changes within the SMG acini that we have termed oncocytic glandular metaplasia (OGM), and necrotizing sialometaplasia-like change (NSMLC). The aim of this study is to evaluate the associated clinicopathological parameters of, and to phenotypically characterize the SMG metaplasias. Esophagectomy specimens were retrospectively assessed on hematoxylin and eosin sections and assigned to either a Barrett's esophagus (BE) or non-BE control group. Clinicopathologic data was collected, and univariate analysis and multivariate logistic regression models were performed to assess the adjusted associations with NSMLC and OGM. Selected cases of SMG metaplasia were characterized. SMG were present in 82 esophagi that met inclusion criteria. On univariate analysis, NSMLC was associated with BE (p = 0.002). There was no relationship between NSMLC and patient age, sex, tumor size, or treatment history. OGM was associated with BE (p = 0.031). No relationship was found between OGM and patient age, sex, or tumor size. On multivariate analysis, BE was independently associated with NSMLC (odds ratio [OR] 4.95, p = 0.003). Treatment history was also independently associated with OGM (p = 0.029), but not NSMLC. Both NSMLC and OGM were non-mucinous ductal type epithelia retaining a p63-smooth muscle actin co-positive myoepithelial cell layer. NSMLC and OGM were present in endoscopic mucosal resection specimens. Our study suggests that SMG metaplasia is primarily a reflux-induced pathology. NSMLC may pose diagnostic dilemmas in resection specimens or when only partially represented in mucosal biopsies or endoscopic resection specimens.

Figure 1. Definition of pathological changes in the esophageal submucosal glands

A: SMG in a pediatric autopsy shows well-developed acini and duct. B: Normal adult SMG residing immediately beneath the muscularis mucosa. C: SMG demonstrating marked oncocytic metaplasia. D: NSMLC; Acute necrotizing phase shows necrosis of the SMG acini. E: NSMLC Stable phase; Ectatic ducts replace the mucous cells of the acini and are accompanied by a dense lymphoplasmacytic infiltrate. F: NSMLC Stable phase; Complete loss of the SMG acini with markedly dilated ducts and stromal desmoplasia-like changes. All H&E staining. (SMG, submucosal glands; NSMLC, necrotizing sialometaplasia-like change)

Figure 2. Distribution of NSMLC within the esophagus

A: Esophagectomy specimen showing NSMLC (arrow) underlying a segment of squamous mucosa in a patient with BE. B: Specimen from an EMR showing NSMLC (large arrow) underlying a segment of erosive esophagitis (small arrow) in a non-BE control patient with GERD. C. Esophagectomy specimen showing NSMLC underlying an intestinalized segment of esophagus in a BE patient. D. EMR specimen showing high grade columnar dysplasia overlying an SMG with NSMLC (Inset is higher power of NSMLC). All H&E staining. (EMR, Endoscopic Mucosal Resection; GERD, gastro-esophageal reflux disease; SMG, submucosal glands; NSMLC, necrotizing sialometaplasia-like change)

Figure 3. Comparison of immunohistochemical and histochemical markers in the metaplastic changes of the esophageal submucosal glands

Serial sections of a normal SMG are displayed in the first row in comparison to OGM in the second row and NSMLC in the third. (AB-PAS, Alcian-Blue Periodic Acid Schiff; SMA, Smooth muscle actin; SMG, submucosal glands; NSMLC, necrotizing sialometaplasia-like change).