A Metachronous Case of Gastric Lymphoma and Gastric Adenocarcinoma

Lyon A (Department of Surgery, Western Infirmary, Glasgow), Crozier J E M (Department of Surgery, Gartnavel General Hospital, Glasgow), Mitchell K G (Department of Surgery, Royal Alexandra Hospital, Paisley

Correspondence to: Alison Lyon, University Department of Surgery, Western Infirmary, Church Street, Glasgow, G11 6NT, email: alisonlyon@doctors.org.uk


The occurrence of gastric adenocarcinoma and gastric lymphoma in the same patient is very rare despite a major shared risk factor in the form of Helicobacter pylori infection. We report on a 48 year old who presented with MALT lymphoma, managed with Helicobacter eradication therapy, who presented with gastric adenocarcinoma ten years later. We suggest that MALT lymphoma patients may require extended follow up, or indeed could benefit from regular H. pylori screening programmes.

Key Words
Gastric adenocarcinoma; Gastric MALT lymphoma; Helicobacter pylori

A 48 year old lady presented in 1997 with haematemesis. She had been diagnosed with a duodenal ulcer six years prior to this attendance. There was no other significant past medical history. She was a smoker of ten cigarettes per day, and drank less than fourteen units of alcohol per week. She underwent upper gastrointestinal (GI) endoscopy and was discovered to have a gastric ulcer on the greater curve of the stomach. The surrounding area showed haemorrhagic gastritis. Biopsies were taken. As the patient was found to have a mild anaemia, she was discharged with ferrous sulphate and omeprazole.

Biopsies revealed a negative CLO test, however on cresyl fast violet staining, a few helicobacter organisms were noted. Furthermore, biopsy appearances were highly suspicious of low grade B cell lymphoma of MALT type. Repeat endoscopy was carried out three months later and revealed the ulcer to be persisting. CLO test was again negative but abundant helicobacter organisms were seen; moreover, a lymphocytic infiltrate highly suspicious of MALT lymphoma was found. She received a course of quadruple therapy which included Amoxicillin, Metronidazole, Lansoprazole and Bismuth for ten days. She was reviewed by the haematologists and multiple investigations were arranged. A CT scan of chest, abdomen and pelvis revealed no local or distal spread, and a bone marrow aspirate was not suspicious of involvement. As she had no evidence of spread, it was decided to carry out serial endoscopies to monitor the lymphoma. Repeat endoscopy showed improvement of the ulcer. Biopsies showed no evidence of helicobacter, but appearances were still suspicious of MALT lymphoma. She continued to undergo surveillance endoscopy, and the ulcer healed with no evidence of disease. She was closely monitored by the haematologists until 2003 when annual endoscopy was discontinued.

She re-attended in 2007 with epigastric discomfort and weight loss. Further upper GI endoscopy was undertaken, revealing an abnormality in the body of the stomach. Biopsies revealed an adenocarcinoma. A CT scan of chest, abdomen and pelvis was carried out which showed abnormal thickening of the stomach wall and a single enlarged lymph node adjacent to the lesser curve (figure 1, figure 2). The patient was discussed at the upper GI multidisciplinary team meeting. A staging laparopscopy was carried out. Peritoneal washings showed no evidence of malignant disease. She underwent neo-adjuvant chemotherapy. Subtotal gastrectomy was carried out. Pathology showed this to be a T2 N1 tumour, with positive greater curve lymph nodes and 2 extranodal deposits of adenocarcinoma in the omentum. There was no evidence of further MALT lymphoma. She underwent further chemotherapy. She is now one year post surgery and is being monitored for evidence of recurrence.

Figure 1: CT scan showing coronal section of abdomen and pelvis demonstrating thickening of stomach wall

 

Figure 2: CT scan showing axial section of abdomen demonstrating enlarged lymph node adjacent to lesser curve of stomach

Discussion
The epidemiology of gastric cancer is evolving. In the 1980’s gastric cancer was the most prevalent cancer worldwide, until it was overtaken by lung cancer in the 1990’s1. Age standardized incidence and mortality rates have been declining over the past four decades in many countries around the world, including Japan and Australia2. However, the workload associated with gastric cancer in the United Kingdom has remained steady, this is attributed to the ageing population3. The ageing population in the UK means it is possible that more cases of patients developing both forms of gastric malignancies discussed will emerge, either metachronously as in this case, or concommitantly.

There are many factors implicated in the aetiology of gastric cancer. Dietary factors are implicated, for example, diets containing reduced intake of fresh fruit and vegetables have been associated with increased risk. High levels of salt and preserved foods have also been suggested as important risk factors. Smoking is another lifestyle factor which has been suggested as a contributing factor to gastric cancer. There is also a known increased risk of two-three times for first degree relatives of a patient with gastric cancer3.

However, the discovery of Helicobacter pylori (H. pylori) in 1983 changed the path of research into gastric cancer. H. pylori is a Gram negative bacillus which can only survive on gastric type mucosa4. It is understood that chronic inflammation of gastric mucosa can result in intestinal metaplasia and gastric atrophy, which are associated pre-cursors to malignant change. This concept was developed in patients previously undergoing gastric resection for benign conditions and those with pernicious anaemia. However, in recent years, there has been increasing evidence to support the role of H. pylori in the development of gastric cancer via this mechanism. It has been shown to cause persistent gastritis, which can progress to a chronic form. Severe atrophic gastritis with associated intestinal metaplasia can subsequently develop3,5. This relationship is supported by epidemiological studies, which have shown declining rates of gastric cancer in developed countries accompanied by falling rates of H. pylori infection6.

Lymphoma of the gastrointestinal (GI) tract is the most common extranodal type, and almost all of these are non-Hodgkin’s type. The stomach is the most commonly involved organ affected in the GI tract4. Most of the non-Hodgkin’s lymphomas originating in the stomach are B cell tumours. These are sub-divided into high grade and low grade lymphomas of mucosa-associated lymphoid tissue (MALT). It has been acknowledged that low and high grade types exist on a spectrum of disease, with low grade progressing into high grade lymphoma. The descriptive term MALT is used as the histology of the low grade B cell lymphomas resembles the structure of Peyer’s patches more closely than that of lymph nodes7.

Normally, in the sites where MALT lymphomas originate there is no lymphoid tissue, however, lymphoid tissue of MALT-type builds up and develops into lymphoma. This build up occurs in the stomach in response to a chronic inflammatory response, typically caused by infection with H. pylori4. Several studies support this, and suggest that H. pylori provides a catalyst via antigenic stimulus promoting growth of gastric MALT lymphoma7. In vitro studies have shown low grade gastric lymphoma to be stimulated by H. pylori and acting through H. pylori-specific T cells. Furthermore, epidemiological studies have shown that gastric lymphoma is more common in a demographic where there are high rates of H. pylori infection. Disease regression has also been reported in 75% of patients with low grade type after eradication therapy4, 7.

It may be that patients with MALT lymphoma require extended follow up. Our patient underwent five years of follow up for her lymphoma. In the United Kingdom the follow up methods are usually determined according to a locally agreed policy within individual areas1. Moreover, this increased risk associated with Helicobacter infection invites questions as to whether a form of H. pylori screening programme for MALT lymphoma patients should be instituted, or indeed if eradication therapy would be of benefit to at risk populations within this group.

References
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