Brunner's Gland Hamartomas: Two Cases of This (Sometimes) Distinctive Lesion.

Brunner's gland hamartomas (BGHs) are rare, benign, primary duodenal tumors. The clinical presentations can vary, and confirming a diagnosis can be challenging because of the submucosal nature of the lesions. We report two cases of BGHs with different clinical presentations. The diagnoses were not determined initially, despite utilizing endoscopy, mucosal biopsies, endoscopic ultrasound, and, in one case, fine-needle aspiration. Confirmation of BGHs was subsequently made following endoscopic or surgical resection.


INTRODUCTION
Brunner's glands are submucosal glands comprised of mucinsecreting cells located primarily in the first portion of the duodenum. 1 These glands are responsible for producing an alkaline secretion with glycoproteins and bicarbonate, which lubricates the duodenal mucosa and protects the epithelium from gastric acid and pancreatic enzymes. 2 Brunner's glands can organize, creating benign polypoid lesions or a nodular appearance of overlying mucosa, which are termed Brunner's gland hyperplasia or Brunner's gland hamartoma (BGH). A BGH is a solitary lesion consisting of Brunner's glands, ducts, smooth muscle, adipose tissue, and lymphoid cells. Brunner's gland hamartomas are uncommon, representing up to 5% of primary duodenal tumors. 3 Risk factors are unclear as there are no known sex or racial predilections, but there may be an association with chronic peptic ulcer disease. 1 Most BGHs are asymptomatic and noted incidentally at the time of endoscopy as a pedunculated polyp, typically less than 3 cm in size. When symptomatic, BGHs most often manifest with symptoms of upper gastrointestinal hemorrhage or obstruction. Bleeding commonly presents as melena, although chronic iron deficiency anemia and hematemesis have been reported. Obstructive symptoms are more common with larger lesions (>2 cm) and can manifest as gastric outlet or duodenal obstruction. 4 All authors participated in the writing and editing of this case report. This case report was a poster presentation at the American College of Gastroenterology Annual Meeting 2016.
Informed consent was obtained from both patients.

CASE 1
A 67-year-old male with a remote history of a duodenal ulcer was admitted to the hospital for melena. He denied early satiety, nausea, vomiting, or abdominal discomfort. Physical and abdominal examinations were unremarkable. Endoscopy revealed a 3-cm sessile mass in the proximal duodenum ( Fig. 1). Mucosal biopsies were performed and were felt to be consistent with a hyperplastic polyp. Given the large size of the lesion, further evaluation was performed with endoscopic ultrasound (EUS), which showed a 31 mm × 25 mm (in cross-sectional diameter) mass in the proximal second portion of the duodenum. The mass had a slightly hyperechoic center and a hyperechoic border, and an intact muscularis propria was observed deep to the mass. Fine-needle aspiration of this lesion was nondiagnostic. Repeat EUS-FNA was subsequently performed, revealing rare atypical spindle cells. Immunohistochemical staining was not performed given the scant cellularity (Fig. 2). At this point, the patient underwent a distal gastrectomy and a proximal duodenectomy with Billroth II reconstruction. The gross specimen revealed a 4.5-cm lesion with focal superficial ulceration. Histologic evaluation revealed a BGH with no evidence of malignancy.

CASE 2
A 56-year-old male with atypical chest pain was evaluated with a cardiac CT, which showed esophageal thickening. The patient denied any upper gastrointestinal or constitutional symptoms, and his physical examination was unremarkable. He underwent a diagnostic endoscopy, which revealed normal esophageal mucosa. He was incidentally noted to have a 12-mm semi-pedunculated polyp in his duodenal bulb (Fig. 3). The polyp prolapsed into the stomach and was seen exuding a milky white fluid. The polyp was biopsied, revealing Brunner's gland hyperplasia, acute inflammation, and foveolar metaplasia. He was referred for further characterization with EUS, which showed a uniformly hyperechoic polyp (Fig. 4). The polyp was resected with hot snare after injection of epinephrine at the base. Pathologic examinations revealed a BGH.

DISCUSSION
Brunner's gland hamartomas comprise up to 5% of primary duodenal tumors. They arise from Brunner's glands, with 70% developing in the duodenal bulb. Although typically asymptomatic, these lesions may cause gastrointestinal bleeding or obstruction. 4 Case reports have also described BGHs acting as a lead point for intussusception and causing pancreaticobiliary obstruction, mimicking pancreatic or ampullary cancer. 5 As observed in our first case, establishing the diagnosis of BGHs can be challenging, as mucosal biopsies and FNA may not be diagnostic because of the submucosal nature of the lesion. A review of the typical features on EUS shows that echogenicity can vary from hypoechoic to hyperechoic and that they are most often heterogeneous in appearance, arising from the submucosa. Surgical or endoscopic resection is often required to confirm diagnosis. 6 The two cases presented here highlight the importance of recognizing the significance of the EUS appearance when these lesions are evaluated with EUS and appear hyperechoic. Most hyperechoic lesions encountered in the gastrointestinal tract are lipomas, which have much different endoscopic appearance than BGHs. Other rare lesions that can have a hyperechoic appearance include hamartomatous polyps, gangliocytic paragangliomas, and renal cell carcinoma metastases. Another distinctive feature of BGHs is the milky white fluid exuding from the lesion, which may be from the production of a cell-free, homogenous fluid that is secreted from the duodenal glands becoming more apparent with the coalesced glands. 7 The hypoechoic EUS appearance and the milky white fluid can help identify these lesions as BGHs, even if tissue sampling is nondiagnostic.
In large lesions that require surgical removal, such as in our first case, suspecting a BGH may allow a more limited resection. For our patient number 1 who underwent surgery, given the sessile nature of the polyp, the atypical cells found on FNA concerning for a gastrointestinal stromal tumor or malignancy, the symptomatic nature of the lesion with bleeding, surgical resection was required but was able to remain limited. Further endoscopic diagnostic studies were unlikely to change the management. In small polypoid lesions, such as in our second case, endoscopic resection is appropriate to allow a definitive diagnosis and prevent the complications that can occur when these lesions become larger.