{'fraction_non_alphanumeric': 0.028730964467005075, 'fraction_numerical': 0.007614213197969543, 'mean_word_length': 5.2308665401644525, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Case report of Brunner’s gland hyperplasia: A rare “mimic” of malignant pathology

Highlights • BGH is a rare, benign condition to consider in a patient with epigastric pain, dyspepsia, weight loss and upper gastrointestinal bleeding.• The diagnosis involves multiple modalities including CT, MRI, endoscopic ultrasound and biopsies.• It is important to determine the correct diagnosis to reduce the risk of overtreating a benign condition.


Introduction
Brunner's glands are exocrine glands that are located in the submucosal layer of the duodenum. Brunner's gland hyperplasia (BGH) is a rare, benign condition of the duodenum that was first described in 1835. It is also known as Brunner's gland hamartoma, adenoma or Brunneroma. It has been rarely described in the literature, with less than 200 cases reported [1]. We report an unusual case of a large BGH, presenting to an Australian public hospital with obstructive symptoms, that mimicked duodenal adenocarcinoma requiring a proximal duodenectomy. This case has been reported in line with the SCARE criteria [2].

Presentation of case
A 60-year-old male presented to our institution's emergency department with nausea, post prandial projectile vomiting and a loss of weight of 12 kg in the preceding 3 months. This was associated with intermittent fevers, and nocturnal diaphoresis.
Past medical history included chronic back pain with intermittent prescriptions of Meloxicam and chronic obstructive pulmonary disease. His past surgical history is unremarkable. * Corresponding author. On examination, he appeared malnourished. He was haemodynamically stable. His abdomen was mildly distended and a succession splash was present. There was no obvious lymph node enlargement.
The patient was not anaemic. Tumour markers including carcinoembryonic antigen, cancer antigen 19-9 and alpha-fetoprotein were unremarkable. Liver function tests were unremarkable and there was no obvious biliary obstruction on imaging. A computed tomography (CT) of the abdomen showed a large soft tissue mass at the second part of the duodenum, with loss of fat plane between the duodenum and uncinate process (Fig. 1). Further imaging including magnetic resonance imaging demonstrated mural thickening involving the duodenal bulb, and possibly D2 segment, without any clear focal pancreatic head lesion (Fig. 2).
A gastroscopy showed a large, mucosally denuded regions in the proximal D2, suggestive of an infiltration lesion rather than ulceration. Biopsies were taken and were suggestive, but not diagnostic of a moderately differentiated adenocarcinoma. An endoscopic ultrasound (EUS) was not performed due to deep biopsy and imaging both being indicative of a malignancy.
The patient was managed with nasogastric tube, total parenteral nutrition and anaesthetic optimisation, with a plan for a laparotomy and pancreaticoduodenectomy.
The procedure was performed by a specialist hepatobiliary surgeon. Intra-operatively, findings were of a stricturing area in the first part of the duodenum, approximately 5 cm from the major papilla. A cholecystectomy was performed, and a catheter inserted   through the cystic duct to confirm the site of the major papilla. A decision was made to perform a proximal duodenectomy given the location of the lesion, with the rationale that sufficient margins would be obtained with a proximal duodenectomy without the morbidity associated with a pancreaticoduodenectomy. The stomach was divided at the Incisura, and the duodenum was divided at the second part of the duodenum, proximal to the papilla, with a T-Tube inserted into the duodenal stump for decompression. Frozen section was not performed due to the pre-operative biopsies being suggestive of adenocarcinoma. A Billroth II anastomosis was performed with a Braun entero-enterostomy. A feeding jejunostomy was inserted at the time of surgery.
Histopathology showed a prominent and diffuse area of near circumferential Brunner's gland hyperplasia, expanding the submucosa. The growth pattern of the glands was expansile rather than infiltrative. Associated with this was an area of ulceration approximately 20 × 20 mm, with a focal perforation noted. All associated lymph nodes were benign. No evidence of malignancy was seen. No evidence of Helicobacter infection was noted.
The patient recovered well postoperatively. He was discharged on a puree diet, upgraded as appropriate and on review at six weeks, his jejunostomy and biliary limb t-tube was removed.

Discussion
Brunner's glands are acinotubular exocrine glands that are located in the submucosal layer of the duodenum [3]. The majority of Brunner's glands are located in the first part of the duodenum, with decreasing prevalence distally through the duodenum. One of their key roles is to secrete mucin, an alkaline fluid which acts to protect the duodenum from the acidic contents entering from the stomach [3].
Brunner's gland hyperplasia (also referred to as adenoma/hamartoma) is a rare lesion found within the duodenum. A report of over 25,000 upper gastrointestinal endoscopies demonstrated an incidence of duodenal polyps in just 1.5% of cases, and of these, BGH accounted for 6.9% [4]. In a case series by Levine et al., the median age of patients with BGH is 56 years old, with a small female preponderance (4:5 male: female) [5]. This study also reported that BGH most commonly occurs in the first part of the duodenum (70%), with decreasing incidence distally [5]. The mechanism of BGH is not entirely clear. The main hypotheses are that BGH is an adaptive response to increased acidity of the stomach contents, chronic Helicobacter pylori infection or secondary to pancreatic exocrine insufficiency.
Typically, most patients with BGH are asymptomatic. However, patients may present with symptoms including dyspepsia, abdominal pain, obstructive symptoms such as post-prandial vomiting and weight loss, or gastrointestinal bleeding. The diagnosis of BGH is difficult to make, with differential diagnoses including an adenomatous polyp, leiomyoma/leiomyosarcoma, gastrointestinal stromal tumour, or pancreatic tumours [1]. There are cases in the literature reporting BGH simulating a carcinoma of the duodenalpancreatic region meaning that they can often be overtreated [6,7].
BGH is often an incidental finding on endoscopy. Endoscopic findings are typically mucosal protrusions or polyps. Unfortunately, biopsies of the duodenal mass can be of limited value. Throughout the literature, there are multiple cases of incorrect diagnoses from biopsies -ranging from normal tissue to well differentiated adenocarcinoma [1,[6][7][8][9][10][11][12]. This is in part due to Brunner's glands being submucosal, with endoscopic mucosal biopsies often not achieving sufficient depth for diagnosis.
CT with IV contrast imaging of BGH typically demonstrates a duodenal mass that is separate from pancreatic parenchyma, however it is often unable to clearly differentiate between BGH and more concerning malignant lesions [1]. Endoscopic ultrasound  [13]. Multiple recent cases demonstrate the role of EUS for BGH, with consistent findings of a hypoechogenic mass in the duodenum [14]. Surgical management of BGH ranges from local endoscopic resection to more extensive surgery. In rare cases patients undergo pancreaticoduodenectomy (Table 1). There is a role for extensive pre-operative work-up, as well as intra-operative assessment to plan for the best management plan for these patients. Thorough examination of the duodenum intra-operatively by the surgeon can reduce the extent of surgery, with cases such as ours initially planned for pancreaticoduodenectomy changed to less extensive surgery based on the intra-operative findings [1,7,15]. Intra-operative frozen section has also been used with varying success to limit the extent of the surgery for a patient with BGH. Reisner and Nava, report an intra-operative frozen section diagnosis of BGH changing management to local tumour resection from the pre-operative plan of pancreaticoduodenectomy [7]. However, Lee et al. were not able to rule out malignancy based on frozen section, so continued with their pre-operative plan for pancreaticoduodenectomy [10].
BGH has typically been considered to be a benign condition of the duodenum. Interestingly however, some cases in the literature have demonstrated the malignant potential of Brunner's gland hyperplasia [16]. This case reports an exceedingly rare entity, and there is debate in the literature whether adenocarcinoma is truly of Brunner's gland origin or that of surrounding tissue. Further description of the progression from hyperplasia to adenocarcinoma is required.

Conclusion
Brunner's gland hyperplasia is a rare condition that can mimic malignant pathology. As seen in this case, our patient underwent a procedure associated with significant morbidity for a benign condition. It is important to consider Brunner's gland hyperplasia as a rare pathology that can cause gastrointestinal bleeding or obstructive symptoms. Extensive pre-operative work-up may be required to determine the nature of the pathology in patients with duodenal masses.

Declaration of Competing Interest
The authors report no declarations of interest.

Sources of funding
None.

Ethical approval
Ethical approval was not required for this case as it is an observation report written after the episode of care.

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Authors contribution
Writing, editing and literature research: Jonathan McCafferty and Ashraf Tokhi.

Registration of research studies
Not Applicable.

Provenance and peer review
Not commissioned, externally peer-reviewed.