Giant Brunner's gland adenoma - an unusual cause of gastrointestinal haemorrhage
VSR Rao, F Rayan, Al-Mukhtar, S Stojkovic, SM Ahmad and PJ Moore
ABSTRACT
Brunner's gland adenoma is a rare benign tumour of the duodenum. Less than 200 cases have been reported in the literature. Usually asymptomatic, these lesions rarely manifest as upper gastrointestinal haemorrhage or duodenal obstruction. We report a 40 year old gentleman who presented with malaena and iron deficiency anaemia. Duodenoscopy revealed a large pedunculated tumour in the duodenal bulb. Due to the huge size, the patient underwent surgical polypectomy through laparotomy and duodenotomy. Histological examination confirmed it to be Brunner's gland adenoma. Endoscopic and radiological features are illustrated along with a literature review of this rare, yet important and easily overlooked cause of gastrointestinal haemorrhage.
Key words: Brunner's gland adenoma; gastrointestinal haemorrhage; brunneroma
INTRODUCTION
Brunner's gland adenoma also known as Brunneroma, is a rare, benign, proliferative lesion arising from the Brunner's glands of the duodenum, usually discovered incidentally at endoscopy. It is believed to be a hamartoma of the brunner's glands - branched acinotubular glands situated in the submucosa of the first part of duodenum which neutralizes acid chyme by its alkaline secretion. They are usually asymptomatic, found incidentally at endoscopy. Occasionally, they cause gastrointestinal haemorrhage or duodenal obstruction necessitating surgical excision. Ensoscopic polypectomy is the treatment of choice, though large size, as in our case may require open surgical polypectomy.
CASE REPORT
A forty year old gentleman presented with complaints of 2-3 episoides of malaena of few days duration. There was associated history of shortness of breath on exertion and lethargy for the last six months. Signifiicant medical history included that of chronic fatigue syndrome and he was not on any regular medications.
Clinical examination was normal, apart from pallor. Routine blood investigations revealed Hb of 8.0 gm/dl and ferritin level of 2.0. Rest of the investigations including chest and abdominal X-rays were normal. As part of his workup, he underwent upper gastrointestinal endoscopy which revealed a smooth polypoidal tumour arising in the duodenal bulb (Fig 1).
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The tumour was biopsied which was reported as normal. Colonoscopy was also normal. Small bowel meal revealed a smooth filling polypoidal filling defect in the first part of duodenum (Fig 2).
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Subsequently, at laparotomy, a soft mobile swelling could be felt within the first part of duodenum. Duodenotomy was performed which revealed a 5 x 3 cm sized pedunculated polypoidal growth arising from the mucosa of first part of duodenum (Fig 3). It was excised and the patient made an uneventful recovery.
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The cut surface of the tumor had a grayish color, revealing multiple cystic spaces and histopathology examination revealed submucosa with numerous brunner's glands in a lobular architecture surrounded by bundles of fibromuscular and connective tissue, confirming the diagnosis of brunner's gland adenoma.
DISCUSSION
Brunner's gland adenomas (BGA), also known as brunneromas are rare benign tumours of the duodenum accounting for about 10.6% of benign duodenal tumors1. Brunner's gland adenoma is an extremely rare but important entity, arising from the brunner's glands of the duodenum, usually discovered incidentally at endoscopy. Since the first reported cases by Curveilhier in 1835 and Salvioli in 1876, less than 200 cases of BGA have been reported in the literature. The first case of a brunner's gland adenoma was described in 1835 by Cruveilhier (1,2). He presented a woman who died from intussusception secondary to obstruction.
Histologically, brunner's glands are branched acinotubular glands located in the submucosa and lined with large cells, the cytoplasm of which stain strongly for mucin and lightly with hematoxylin and eosin staining. The normal function of brunner's gland is to secrete alkaline secretion which empty into the Crypts of Lieberkuhn in the duodenum and protects the duodenal mucosa from the damaging action of acid chyme 3. The distribution of these glands is mostly proximal to the ampulla of Vater, with most of them being just distal to the pylorus. In infants, they constitute 55% of the total duodenal area. By 50 years of age, this declines to 35% 2.
Hence the main function of brunner's gland is to secrete an alkaline fluid that helps neutralize acid. This fluid also contains a glycoprotein that binds tightly to cover the mucosal surface 3. Furthermore, brunner's glands produce and secrete an enteric hormone - enterogastrone, which is an inhibitor of gastric acid secretion. Thus, it is thought that they perhaps play a role in duodenal resistance to ulcer formation.
Brunner's gland adenomas are most commonly located in the duodenal bulb, with the second and third portions of the duodenum being much less affected 4. Usually small in size, only a few cases more than 4 to 5 cm in size have been reported in the literature. Their usual size is 1 to 2 cm, although great variations in size varying from a few millimeters to several centimeters may occur, with one report indicating the size of the adenoma to be 12 × 10 × 8 cm 5. Hyperplasia of brunner's gland is differentiated from adenoma based on size. Lesions less than 1 cm represent hyperplasia, whereas those more than 1 cm are called adenoma 6.
The exact pathogenesis of brunner's gland adenoma still remains unclear. Some have suggested that the brunner's glands are stimulated to undergo hyperplasia by increased acid secretion 7. No studies to date confirm this view. One investigation found that there was no correlation between the occurrence of these adenomas and gastric hyperacidity found in duodenal ulcers 8, whereas another study showed that the adenomas do not regress after H2-receptor blocker therapy 1. Studies suggest that concurrent H. pylori infection is very common in patients with Brunner's gland adenoma. However, the role of H. pylori infection in the pathogenesis and development of brunner's gland hyperplasia remains unclear 9. Another theory holds that these lesions are formed by hyperplastic reactions to inflammation 8. Although foci of inflammatory cell infiltrates have been found in these lesions, lymphocytes are normally found in the submucosa throughout the entire length of the gastrointestinal tract. Therefore, the mere presence of lymphocytes is insufficient evidence for this argument. Brunner's gland adenoma with a focus of p53-positive atypical glands has been described 10. Studies have reported brunner's gland adenoma with foci of microcarcinoids 11. Some studies have reported that Pascual's argyrophilic (PAP) test discovered focal hyperplasia of endocrine cells in the intestinal lining. The majority of these cells, according to PAP reactions with antisera to polypeptides, were serotonin-positive. Among tumor cells, somatostatin-positive cells were most numerous 12.
Thus controversy exists over its etiology and pathogenesis, but the present view is that BGA represent hamartomas in the duodenum, with a predominance of Brunner's gland elements along with a mixture of smooth muscle, acini, adipose tissue, Paneth cells, and mucosal glands. The adenoma develops into a polypoid mass that is unencapsulated, elongated, and lobulated. They may be sessile or pedunculated. Importantly, they retain an intact duodenal mucosa with no discrete demarcation from the adjacent normal brunner's glands Benign, proliferative changes of the brunner's gland are very rare and account for about 10% of duodenal bulb neoplasias. They are occasionally associated with gastric hyperchlorhydria or chronic pancreatitis.. Malignancy seems to occur only very rarely, with only 14 cases reported in the literature 13.
Patients with BGA usually present in the 4th to 6th decade of life. Most are asymptomatic or present with nonspecific, vague abdominal pain or discomfort, nausea, or bloating. These patients are diagnosed incidentally, when imaging studies or endoscopy are done for evaluation of their symptoms. Thus, usually they present as incidental findings in the form of small polypoid lesions at barium examination or at panendoscopy.
Clinically significant presentations include hemorrhage and obstruction 3. The clinical presentation can vary from vague upper abdominal symptoms with dyspepsia and nausea to diarrhea, jaundice, obstruction, and gastrointestinal bleeding. Anemia results from intermittent chronic blood loss secondary to ulceration from the mucosa overlying the mass. Patients may present with high-output congestive heart failure secondary to profound iron deficiency anemia. Uncommon manifestations include palpation of an abdominal mass 4, obstructive jaundice 14, biliary fistula 15, recurrent pancreatitis 16, and intussusception 17. Brunner's gland adenomas may rarely mimic pancreatic cancer 14. A few patients present with severe acute gastrointestinal bleeding in the form of melena and/or hematemesis with or without hemodynamic compromise 18.
The diagnosis is usually made by radiological studies followed by upper gastrointestinal endoscopy, which can also provide definitive treatment. Upper gastrointestinal barium studies may reveal a duodenal filling defect, seen as a "vacuole sign" - smooth-walled, polypoid-filling defects, sessile or pedunculated, in the bulb or corresponding portion of the duodenum 1,8,19. However, this study is not definitive because many other lesions mimic a similar picture. Endoscopy demonstrates the tumor in the duodenal lumen and facilitates biopsy from the lesion, which is usually negative owing to the submucosal location of the tumor. Hence, although endoscopy has improved the diagnosis of the duodenal tumors, traditional endoscopic pinching biopsy does not always make a histological diagnosis. Endoscopic biopsy is usually negative because the tumor is located completely in the submucosa and hence the biopsy forceps is unable to reach into the tumor tissue.
Endoscopic ultrasound helps to differentiate between intraluminal and extraluminal growths and to establish a preliminary diagnosis depending on the layer from which a particular lesion arises and also from the characteristic appearance of the lesion. It can also detect involvement of the surrounding structures and the presence of metastasis. Endoscopic ultrasound appearance of Brunner's gland hamartoma has been described as involvement of only the mucosa and submucosa-a smooth border and variable echogenicity, which represents the dilated glands seen within the tumor 20. Computed tomography can be used to delineate the extraluminal extent of large adenomas and to show their relationship to the pancreas, common bile duct, and inferior vena cava 21.
The differential diagnosis includes leiomyoma, lipoma, carcinoid tumor, lymphoma, aberrant pancreatic tissue, prolapsed pyloric mucosa, and even a foreign object. Confirmation of the diagnosis requires biopsy and histological examination.
Endoscopic or surgical removal of the adenoma has been suggested in symptomatic patients to prevent development of complications. These include intussusception, when the adenoma may act as a lead point and cause the duodenum to telescope on itself. If the adenoma is located near the ampulla of Vater, it may lead to biliary obstruction. Extensive hemorrhage from ulcerated tissue may cause chronic anemia and may even require immediate transfusion if the bleeding is severe enough.
Local excision of the lesion is the main treatment. This may be done by either a endoscopic snare-cautery technique or excision of the mass via duodenotomy. The former method is more cost-effective, less invasive, and has reduced risks of abdominal surgery 22,23. Several cases of successful endoscopic resection of pedunculated BGA have been reported 24. It is important to identify the ampulla of Vater before initiating the endoscopic procedure 7,8,22. As the majority of Brunner's adenomas are quite small, endoscopic polypectomy will confirm the diagnosis and cure the condition in most cases. However, if the size and the anatomic location makes endoscopic removal more difficult or impossible, excision via duodenotomy must be performed. Diffuse involvement may require partial resection of the duodenum.
CONCLUSION
Brunner's gland adenomas are rare occurrences that are benign in almost all reported cases. Symptoms are often due to obstruction or ulceration of the lesion within the duodenum. Total removal of the lesion leads to minimal morbidity because it eliminates the risks of complications. However remote the chances, pathological examination of the lesion is essential to exclude malignancy of the lesion after its removal.
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