Duodenal mucosal damage is associated with proliferative activity of Brunner's gland hamartoma: a case report

Abstract

Background: Brunner's gland hamartoma is a rare tumor, predominantly found in the fifth to sixth decades of life. Generally, it is a single pedunculated polyp, rarely larger than 5 cm. Asymptomatic cases are found incidentally, but cases with a large polyp tend to have gastrointestinal bleeding and/or obstructive symptoms. Polyp size increases in a time-dependent manner, however, the growth mechanism is unknown. We report a Japanese male case in his mid-twenties with an over 6 cm sized polyp.

Case presentation: A 26-year-old man presented black stools and anemia. Endoscopic examination revealed a large pedunculated polyp at gastroduodenal junction. The polyp, subsequently resected by distal gastrectomy, was lobulated with random surface erosions and sized 6.4 × 3 cm. Histological examination revealed that the polyp arose from duodenal mucosa and was composed of hyperplastic Brunner's glands in lobules separated by fibromuscular septa, associated with lymphocytic infiltrate and lymphoid follicles. No evidence of malignancy was found. Thus, the lesion was diagnosed as Brunner's gland hamartoma. Further immunohistochemical studies indicated that gastric foveolar metaplasia is associated with surface epithelium covering upper two thirds of the polyp, showing immunohistochemical positivity for mucin 5 AC (MUC5AC). Below the metaplastic surface epithelium, Brunner's glands had high proliferative activity (MIB-1 labeling index: 7.9%). The similar staining pattern was observed at surface erosive sites (MIB-1 labeling index in Brunner's glands: 9%). On the other hand, surface epithelium in the lower side of the polyp still preserved intestinal nature, containing CDX2-positive nuclei and MUC2-positive goblet cells. Brunner's glands below the surface epithelium with intestinal characteristics showed low proliferative activity (MIB-1 labeling index: 0.77%).

Conclusion: Proliferative activity of Brunner's glands was high at the sites with surface erosion and also below the epithelium showing gastric foveolar metaplasia. As gastric foveolar metaplasia occurs along with a mucosal repair process in the duodenum, mucosal damages underlay the hamartomatous proliferation of Brunner's glands and eventually resulted in a formation of large polypoid mass in this case.

Figure 1

Endoscopic image and gross findings. (A) Endoscopic image showing a large polyp at gastroduodenal junction. The polyp head was incarcerated toward duodenal lumen. Hemorrhage was noted in part of the surface. (B) Surgically resected specimen showing a single lobulated and pedunculated polyp. Hemorrhage and erosion are associated. (C) Cut surface of the polyp is white and solid showing lobular structure and a broad fibrous stalk.

Figure 2

Histological findings of the resected specimen. (A) Hyperplastic Brunner’s glands in lobules are separated by fibromuscular septa. HE stain, 40× (B) Lymphocytic infiltrate is observed and a lymphoid follicle is formed between lobules of Brunner’s glands at the center. Arrow indicates a cystically dilated duct. HE stain, 40× (C) Acini and ducts are well-preserved without nuclear atypia. HE stain, 200×.

Figure 3

Immunohistochemical findings of the resected specimen. Duodenal mucosa in the upper part of the polyp (A - D), with erosion (E - H), and in the lower part of the polyp (I - L) are shown in HE stain (A, E, and I), MUC5AC (B and F), MUC6 (C and G), MIB-1 (D, H and L), CDX2 (J), and MUC2 (K) immunostains. Surface epithelium in the upper part of the polyp is histologically similar to gastric foveolar epithelium and immunohistochemically positive for MUC5AC, suggesting gastric foveolar metaplasia (B), and the epithelium in the deeper portion and Brunner’s glands are positive for MUC6 (C). This area shows high MIB-1 labeling (D). The similar staining pattern is observed in the mucosa with erosion (E - H). Surface epithelium in the lower part of the polyp shows a villous structure, containing CDX2-positive nuclei (J) and MUC2-positive goblet cells (K), suggesting preservation of the intestinal nature. MIB-1-positive Brunner’s glands are inconspicuous in this area (L). All images are 40× magnification.

Figure 4

MIB-1 labeling in Brunner’s glands. Representative immunostain images of Brunner’s glands below surface epithelium associated with gastric foveolar metaplasia (A), below erosion (B), and below surface epithelium preserving intestinal nature (C) are shown. Brunner’s glands in (C) are rarely positive for MIB-1, compared to those in (A) and (B). All images are 100× magnification.