Contributed by Scott M Kulich MD, PhD and Sydney Finkelstein, MDFINAL DIAGNOSIS:
POORLY DIFFERENTIATED GASTRIC ADENOCARCINOMA WITH METASTATIC DISEASE INVOLVING THE COLON ARISING IN A BACKGROUND OF CHRONIC ACTIVE GASTRITIS WITH INCOMPLETE INTESTINAL METAPLASIA WITH HEAVY COLONIZATION BY HELICOBACTER PYLORI.
Contributor's Note:
Although there has been a steady decline in its overall incidence during the recent past, gastric carcinoma remains the second most common cause of cancer-related death on a worldwide basis. Epidemiologic studies from high incidence areas such as Japan and Finland have shed light on some of the etiologic factors which play a role in the development of gastric carcinoma involving the fundus and antrum. Chronic atrophic gastritis has been reported in up to 95% of the cases of gastric carcinoma involving the fundic and antral regions. Two of the better characterized forms of chronic gastritis, diffuse corporal atrophic gastritis and multifocal atrophic gastritis, which are often associated with pernicious anemia and Helicobacter pylori infection respectively, are often associated with intestinal metaplasia. Intestinal metaplasia has been categorized as complete versus incomplete based upon the presence of well-formed microvilli and Paneth cells in the complete form of metaplasia. It is the incomplete form of intestinal metaplasia that is believed to be an important precursor to the development of gastric carcinoma. Others have attempted to further subdivided incomplete metaplasia based upon the mucin content of the columnar cells reporting the risk of developing gastric carcinomas in incomplete intestinal metaplasia is highly associated with columnar cells containing sulfomucins ("type III" metaplasia). The link between the development of gastric carcinoma and conditions such as partial gastrectomies, Menetrier's disease, gastric adenomatous polyps, and genetic/environmental factors is less well established.
Lauren subcategorized gastric carcinomas of the fundic and antral regions based upon histologic features into two groups, intestinal and diffuse. This classification is useful since these lesions have different epidemiologic and clinical characteristics. In general, intestinal carcinomas occur most frequently within the antrum, have a higher incidence in males, tend to have a polypoid/ fungating gross appearance with an expansile growth pattern, are usually associated with intestinal metaplasia, occur in older individuals, are associated with environmental factors, and tend to metastasize via lymphatics and along peritoneal surfaces. On the other hand, diffuse carcinomas occur most frequently within the fundus, tend to have a ulcerative/infiltrative gross appearance with an infiltrative growth pattern, are not usually associated with intestinal metaplasia, occur in younger individuals, may have an underlying genetic predisposition, and tend to metastasize via the vasculature to the liver, lungs, and bone. However, the usefulness of this classification scheme is limited since approximately 15% of these tumors have overlapping histologic features.
While the incidence of gastric carcinomas as a whole has declined, gastric adenocarcinoma of the gastric cardia has been steadily increasing and currently accounts for 1/3 of all gastric carcinomas. From a clinicopathologic stand point, many of the risk factors for this type of gastric carcinoma are similar to esophageal adenocarcinoma (lower mean age, association with gastroesophageal reflux and duodenal ulcers, white male predominance, rarely associated with atrophic gastritis), another entity which has been increasing in incidence.
The present case nicely illustrates the typical clinical presentation of this disease. Gastric carcinomas usually remains clinically silent in the early and potentially curative stages of the disease with the onset of vague clinical symptoms such as weight loss and abdominal pain, as seen in this patient, are the most frequent clinical symptoms and unfortunately most frequently occur only after the disease has significantly progressed. While diarrhea is not a typical presenting symptom, lower gastrointestinal complaints such as melena may be present in up to 20% of the cases. The disease can spread to adjacent organs via direct extension or to more distant sites via the peritoneal surfaces, lymphatics, or vasculature. The ability of the diffuse subtype of gastric carcinoma to exist and metastasize as single discohesive cells may result in subtle histologic abnormalities which can lead to diagnostic difficulty which can be minimized with the appropriate clinical suspicion and a well-trained eye.
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Contributed by Scott M Kulich MD, PhD and Sydney Finkelstein, MD
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