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. 2015 Dec;67(6):771-82.
doi: 10.1111/his.12707. Epub 2015 Jun 4.

Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma

Katherine S Garman  1   2   3 , Leandi Kruger  1 , Samantha Thomas  4 , Marzena Swiderska-Syn  1 , Barry K Moser  4 , Anna Mae Diehl  1   2 , Shannon J McCall  2   5
Affiliations

Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma

Katherine S Garman et al. Histopathology. 2015 Dec.

Abstract

Aims: Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individuals with and without oesophageal adenocarcinoma (EAC).

Methods and results: We performed histological assessment of 343 unique ESMGs from 30 control patients, 24 patients with treatment-naïve high-grade columnar dysplasia (HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist assessed haematoxylin and eosin-stained ESMG images by using a scoring system that assigns individual ESMG acini to five histological types (mucous, serous, oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%) (P = 0.006). We also identified greater proportions of acini with dilation (21.9%, P < 0.001) and, to a lesser extent, ductal metaplasia (4.3%, P = 0.001) in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to occur in areas of mucosal ulceration or tumour.

Conclusions: We found a clear association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative progenitor cells, these associations could have significance for understanding the pathogenesis of EAC.

Keywords: Barrett's oesophagus; ductal metaplasia; oesophageal neoplasm; oesophageal submucosal gland; oesophagus.

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Conflict of interest statement

Conflicts of Interest Statement: None of the authors have conflicts of interest to report.

Figures

Figure 1
Figure 1
Normal-appearing ESMG from a control with no history of esophageal cancer: A. A 40× magnification image with squamous epithelium is present, and an esophageal duct is seen reaching in the direction of the ESMG to the lumen of the esophagus. This ESMG demonstrates predominantly non-dilated mucinous acini and there is no evidence of inflammation in this ESMG. B. 200× magnification demonstrates normal appearing mucinous acini without discernible lumens. C. Serous cell with light pink cytoplasm in a different ESMG from the same autopsy case (arrow).
Figure 2
Figure 2
ESMGs containing oncocytic acini from controls: Oncocytes appear densely eosinophilic with a centrally located nucleus. A. 100× view of an ESMG containing 70% oncocytic acini, present on the left (arrows). Mucinous acini, characterized by their pale mucosa are present right side of this ESMG. B. 200× view of oncocytes from Panel A. C. 40× view of ESMG that contains 25% oncocytic acini. D. 40× view of ESMG containing 62% oncocytic acini.
Figure 3
Figure 3
Dilated acinar phenotype (A, B, D, E) and Ductal metaplasia (C and F). A. 40× view of H& E of ESMG from a patient with BE with high-grade dysplasia; 88% of the acini were scored as dilated. B. 100× view of same ESMG with H&E illustrating dilated mucinous glands. C. 100× view of ESMG from an EAC patient with 84% ductal metaplastic acini and prominent inflammation. D. 40× view of CK7 staining illustrating contrast between dilated mucinous glands and more densly staining ducts of ESMG shown in panel A. E. 100× view of same ESMG illustrating dilated mucinous glands with CK7 staining; the arrow in panel E indicates normal CK7 pattern in dilated mucinous acini.. F. 100× view of CK7 staining of ductal metaplasia and inflammation within the ESMGs shown in Panel C; the arrow in panel F indicates ductal pattern of prominent cytoplasmic CK7 staining. Both patients had BE with high-grade dysplasia and EAC and both were treatment naive (no radiation or chemotherapy) prior to esophagectomy.
Figure 4
Figure 4
Examples of different grades (0–3) of ESMG inflammation: Numbers on the images represent the ESMG inflammation score. Arrows indicate inflammatory infiltrate within ESMGs. As shown in panel 3, lymphoid follicle formation is designated grade 3 (arrow).
Figure 5
Figure 5
Proposed progression of ESMG from normal, development of ductal dilation and then ductal metaplasia. A. Normal ESMG B. ESMG with ductal dilation and early ductal metaplasia C. Ductal metaplasia
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References

    1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–146. - PubMed
    1. Howlader N, Noone AM, Krapcho M, et al. Seer cancer statistics review. Bethesda, MD: National Cancer Institute; 2011. based upon November 2010 SEER data submission.
    1. Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ. American gastroenterological association medical position statement on the management of barrett's esophagus. Gastroenterology. 2011;140:1084–1091. - PubMed
    1. Dulai GS, Guha S, Kahn KL, Gornbein J, Weinstein WM. Preoperative prevalence of barrett's esophagus in esophageal adenocarcinoma: A systematic review. Gastroenterology. 2002;122:26–33. - PubMed
    1. Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with barrett's esophagus. N Engl J Med. 2011;365:1375–1383. - PubMed

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