Pathology Lab VI - Chronic Gastritis


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Pathology Lab VI - Chronic Gastritis

  1. 1. Loading, Please Wait ... <br /> Pathology Lab VI - Chronic Gastritis & Gastric Cancer<br />Pathology Lab VI - Chronic gastritis, gastric cancer<br />Igor Danelisen<br /> <br />CASE PRESENTATION: Bobby G <br />Objectives: <br />Discuss the general pathology of gastric cancer. Define staging criteria for gastric cancer. Discuss the pathological and clinical features of gastric adenocarcinoma. Define chronic gastritis and discuss the role of H. Pylori in the pathogenesis of chronic gastritis. Define autoimmune gastritis and discuss the pathogenesis of pernicious anemia. What are the hyperplastic and inflammatory polyps in the stomach? Please define gastric adenomas.<br />Reference:Robbins and Cotran: Pathologic Basis of Disease (8h Edition) pp. 776-781; <br />Bobby G, a 58-year-old plumber, visited his family physitian office with a chief complaint of epigastric discomfort. On physical examination, the abdomen was soft and flat with neither palpable mass nor tenderness. No peripheral lymphadenopathy was observed. Bobby was referred to the GI specialist. Endoscopic examination revealed a protuding lesion 1.5 cm in diameter with a well defined margin on the anterior wall of the gastric antrum. A biopsy sample taken from the lesion was not diagnosed histologically as malignant. Follow-up endoscopic examination after 7 months demonstrated that the tumor had increased in size to 2.0 cm in diameter. Most of the tumor surface was covered with apparently normal gastric mucosa and a shallow recess with mild erosion was observed on the top. <br />Normal gastric mucosa, but not tumor tissue, was obtained by repeated bouling biopsy. Double-contrast radiography showed a tumor mass 2.0 cm in diameter with a well defined border on the greater curvature of the gastric antrum. CT demonstrated a tumor mass with a distinct border on the anterior wall of the stomach.<br />CT and US showed no findings suggestive of lymph node or liver metastasis. Laboratory examination revealed an elevated CA19-9 level of 106.9 U/ml; the level of carcinoembryonic antigen (CEA) was within normal limits. <br />Bobby was then referred to the general surgeon and was scheduled for surgery. Although a histological diagnosis was not achieved before surgery, subtotal gastrectomy with regional lymph node dissection was performed after obtaining informed consent from the patient since gastric cancer was highly suspected in view of the markedly elevated level of CA19-9 and the irregular tumor margin demonstrated by US.<br />The resected specimen was a protuberant tumor 2.0 cm in diameter and was observed on the anterior wall of the gastric antrum. The tumor surface was covered with apparently normal mucosa which was reddish in comparison with the surrounding mucosa. The recess found on endoscopic examination was unremarkable. The tumor was exposed on the serosa of the stomach. Macroscopic stagings according to the TNM classification was T3N0M0 (stage II).<br />The histological diagnosis was papillo-tubular adenocarcinoma infiltrating the serosa. The tumor was located mainly under the mucosa and only a small part of it was exposed. Papillo-tubular adenocarcinoma with a reticulated gland structure was found in the lamina propria mucosae, while less differentiated adenocarcinoma with abundant edematous fibrosis was observed in the submucosal layer . Lymphatic and vascular vessel infiltration was remarkable but no metastasis was evident histologically in the regional lymph nodes. <br />The patient was discharged in the second postoperative week without complication. No recurrence has been observed during a follow-up period of 1 year and 6 months after the operation. <br />Diagnosis: Gastric cancer <br />GASTRIC CANCER<br />Epidemiology: Gastric cancer remains one of the most common forms of cancer worldwide.<br />         Gastric cancer is a second most common cancer in the world behind the lung cancer. <br />         The worldwide incidence of gastric cancer has declined rapidly over the recent few decades. <br />o   Part of the decline may be due to the recognition of certain risk factors such as H. pylori and other dietary and environmental risks. However, the decline clearly began before the discovery of H. pylori. <br />o   An interesting hypothesis is that the popularization of refrigerators marks a pivotal point for the decline. Refrigerators improved the storage of food, thereby reducing salt-based preservation of food and preventing bacterial and fungal contamination. Refrigeration also allowed for fresh food and vegetables to be more readily available, which may be a valuable source of antioxidants important for cancer prevention.<br />o   One possible explanation is the decreased consumption of dietary carcinogens, such as N-nitroso compounds and benzo[a]pyrene, because of reduced use of salt and smoking for food preservation<br />         Despite the decline, the absolute number of new cases per year is increasing, mainly due to increasing life span in the world population.<br />         The incidence of gastric cancer varies with different geographic regions. The highest incidence rates are in Eastern Asia, the Andean regions of South America, and Eastern Europe while the lowest rates are in North America, Northern Europe, and most countries in Africa and South Eastern Asia. There is also substantial difference in the incidence among different ethnic groups within the same region. <br />Clinical features: Most patients with gastric cancer in the US are symptomatic and already have advanced incurable disease at the time of presentation. <br />         At diagnosis, approximately 50 percent have disease that extends beyond locoregional confines, and only one-half of those who appear to have locoregional tumor involvement can undergo a potentially curative resection. <br />         Surgically curable early gastric cancers are usually asymptomatic and only infrequently detected outside the realm of a screening program. <br />         Screening is not widely performed, except in countries which have a very high incidence, such as Japan, Venezuela, and Chile.<br />Initial Clinical Presentation: <br />         Weight loss and persistent abdominal pain are the most common symptoms at initial diagnosis.<br />A.     Weight loss usually results from insufficient caloric intake rather than increased catabolism and may be attributable to anorexia, nausea, abdominal pain, early satiety, and/or dysphagia. <br />B.     Abdominal pain tends to be epigastric, vague and mild early in the disease but more severe and constant as the disease progresses. <br />         Dysphagia (difficulty swallowing) is a common presenting symptom in patients with cancers arising in the proximal stomach or at the esophagogastric junction. <br />         Patients may also present with nausea or early satiety from the tumor mass or in cases of an aggressive form of diffuse-type gastric cancer called linitis plastica, from poor distensibility of the stomach.<br />         They may also present with a gastric outlet obstruction from an advanced distal tumor.<br />         Occult gastrointestinal bleeding with or without iron deficiency anemia is not uncommon, while overt bleeding (ie, melena or hematemesis) is seen in less than 20 percent of cases. <br />         The presence of a palpable abdominal mass is the most common physical finding and generally indicates long-standing, advanced disease.<br />         Approximately 25 percent of patients have a history of gastric ulcer. All gastric ulcers should be followed to complete healing, and those that do not heal should undergo resection <br />Signs of tumor extension:<br />         Since gastric cancer can spread via lymphatics, the physical examination may reveal a left supraclavicular adenopathy (a Virchow's node) which is the most common physical examination finding of metastatic disease, a periumbilical nodule (Sister Mary Joseph's node), or a left axillary node (Irish node). <br />         Peritoneal spread can present with an enlarged ovary (Krukenberg's tumor) or a mass in the cul-de-sac on rectal examination (Blumer's shelf ). <br />         Ascites can be the first indication of peritoneal carcinomatosis. <br />         A palpable liver mass can indicate metastases, although metastatic disease to the liver is often multifocal or diffuse.<br />         Liver involvement is often, but not always, associated with an elevation in the serum alkaline phosphatase concentration. <br />         Jaundice or clinical evidence of liver failure is seen in the preterminal stages of metastatic disease <br />Diagnosis: Tissue diagnosis and anatomic localization of the primary tumor are best obtained by upper gastrointestinal endoscopy .<br />         The early use of upper endoscopy in patients presenting with gastrointestinal complaints may be associated with a higher rate of detection of early gastric cancers. <br />         The ability to perform biopsy during endoscopy adds to its clinical utility. <br />         Since up to 5 percent of malignant ulcers appear benign grossly, it is imperative that all such lesions be evaluated by biopsy and histologic assessment.<br />         Need for follow-up endoscopy for gastric ulcers <br />o   Most of the literature supporting the need for endoscopic follow-up of gastric ulcers to document healing is based upon older surgical and radiologic, rather than endoscopic data. <br />o   More recent studies have called into question the common practice of repeat endoscopy to verify posttreatment gastric ulcer healing<br />         Anatomic localization of the primary tumor can also be obtained by barium studies. <br />o   Barium studies can identify both malignant gastric ulcers and infiltrating lesions, and some early gastric cancers also may be seen. <br />o   However, false-negative barium studies can occur in as many as 50 percent of cases. <br />o   In most settings, upper endoscopy is the preferred initial diagnostic test for patients in whom gastric cancer is suspected. <br />Staging- Systems: <br />         There are two major classification systems currently in use for gastric cancer. <br />         The most elaborate, the Japanese classification, is based upon refined anatomic location, particularly of the lymph node stations. <br />         The other staging system, developed jointly by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC), is the classification most often used in the Western hemisphere and increasingly, in Asian countries as well.<br />TNM staging criteria<br />         The staging schema of the AJCC/UICC is based on tumor (T), node (N), and metastasis (M) classifications. <br />         T stage is dependent on depth of tumor invasion and not size. Nodal stage is based upon the number of positive lymph nodes rather than the proximity of the nodes to the primary tumor (as in the TNM classifications used prior to 1997). <br />         Patients who have no obvious visceral metastases but who have 16 or more pathologically involved nodes are classified as having stage IV disease, which accurately reflects the poor prognosis for these patients.<br />Japanese Classification of Gastric cancer lesions: <br />TNM Classification of Gastric cancer lesions:<br />Important Note: <br />About 85% of stomach cancers are adenocarcinomas, with 15% due to lymphomas and gastrointestinal stromal tumors (GIST) and leiomyosarcomas.<br />GASTRIC ADENOCARCINOMA <br />Epidemiology: Adenocarcinoma is the most common malignancy of the stomach, comprising over 90% of all gastric cancers.<br />         Early symptoms resemble those of chronic gastritis, including dyspepsia, dysphagia, and nausea. <br />         As a result, these tumors are often discovered at advanced stages, when symptoms such as weight loss, anorexia, altered bowel habits, anemia, and hemorrhage trigger further diagnostic evaluation.<br />Pathogenesis: While the majority of gastric cancers are not hereditary, the mutations identified in familial gastric cancer have provided important insights into mechanisms of carcinogenesis in sporadic cases. <br />         Germline mutations in CDH1, which encodes E-cadherin, a protein that contributes to epithelial intercellular adhesion, are associated with familial gastric cancers, which are usually of the diffuse type. <br />         Mutations in CDH1 are present in about 50% of sporadic cases of diffuse gastric tumors, while E-cadherin expression is drastically decreased in the rest, often by methylation of the CDH1 promoter. Thus, the loss of E-cadherin function seems to be a key step in the development of diffuse gastric cancer. Notably, CDH1 mutations are also common in sporadic and familial lobular carcinoma of the breast, which also tends to infiltrate as single cells, and individuals with BRCA2 mutations are at increased risk of developing diffuse gastric cancer.<br />         In contrast to diffuse gastric tumors, there is an increased risk of intestinal-type gastric cancer in individuals with FAP, particularly in Japan. <br />         This implies an interaction between host genetic background and environmental factors, since gastric cancer risk is less markedly elevated in individuals with FAP residing in areas of low gastric cancer incidence<br />         Genetic variants of pro-inflammatory and immune response genes, including those that encode IL-1-beta, TNF, IL-10, IL-8, and Toll-like receptor 4 (TLR4), are associated with elevated risk of gastric cancer when accompanied by H. pylori infection, and p53 mutations are present in the majority of sporadic gastric cancers of both histologic types. <br />Morphology-Gross: Gastric adenocarcinomas are classified according to their location in the stomach, and most importantly, according to gross and histologic morphology. <br />         Most gastric adenocarcinomas involve the gastric antrum; the lesser curvature is involved more often than the greater curvature.<br />Morphology-Microscopy: Important-Classification according to histological morphology:<br /> <br />1. Gastric tumors with an intestinal morphology <br />         Tend to form bulky tumors composed of glandular structures<br />         The intestinal type resembles small bowel mucosa<br />         Although intestinal-type adenocarcinomas may penetrate the gastric wall, they typically grow along broad cohesive fronts to form either an exophytic mass or an ulcerated tumor. <br />         The neoplastic cells often contain apical mucin vacuoles, and abundant mucin may be present in gland lumens.<br />2. Cancers with a diffuse infiltrative growth pattern <br />  Are more often composed of signet-ring cells <br />  These cancers are is generally composed of discohesive cells that do not form glands but instead have large mucin vacuoles that expand the cytoplasm and push the nucleus to the periphery, creating a signet-ring cell morphology. <br />  These cells permeate the mucosa and stomach wall individually or in small clusters, which makes tumor cells easy to confuse with inflammatory cells, such as macrophages, at low magnification. <br />         Extracellular mucin release in either type of gastric cancer can result in formation of large mucin lakes that dissect tissue planes.<br />         A mass may be difficult to appreciate in diffuse gastric cancer, but these infiltrative tumors often evoke a desmoplastic reaction that stiffens the gastric wall and may provide a valuable diagnostic clue. <br />o   When there are large areas of infitration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastic. <br />o   Breast and lung cancers that metastasize to the stomach may also create a linitis plastica–like appearance.<br />Clinical presentation: <br />A.     Intestinal-type gastric cancer <br />         Predominates in high-risk areas and develops from precursor lesions including flat dysplasia and adenomas. <br />         The mean age of presentation is 55 years<br />         The male-to-female ratio is 2 : 1. <br />B.     Diffuse gastric cancer <br />         There are no identified precursor lesions, and the disease occurs at similar frequencies in males and females.<br />Clinical presentation was already described in previous paragraph but we can recap the major symptoms associated with both of these conditions: <br />Early symptoms <br />         Indigestion or a burning sensation (heartburn) <br />         Loss of appetite, especially for meat <br />Advanced disease symptoms <br />         Abdominal pain or discomfort in the upper abdomen <br />         Nausea and vomiting <br />         Diarrhea or constipation <br />         Bloating of the stomach after meals <br />         Weight loss <br />         Weakness and fatigue <br />Bleeding (vomiting blood or having blood in the stool) which will appear as black. This can lead to anemia. <br />Dysphagia; this feature suggests a tumor in the cardia or extension of the gastric tumor in to the esophagus. <br />These can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue. Diagnosis should be done by a gastroenterologist or an oncologist.<br />Metastatic potential: The depth of invasion and the extent of nodal and distant metastasis at the time of diagnosis remain the most powerful prognostic indicators for gastric cancer.<br />         In advanced cases gastric carcinoma may first be detected as metastases to the supraclavicular sentinel lymph node, also called Virchow's node. <br />         Gastric tumors can also metastasize to the periumbilical region to form a subcutaneous nodule, termed a Sister Mary Joseph nodule, after the nurse who first noted this lesion as a marker of metastatic carcinoma. <br />         Local invasion into the duodenum, pancreas, and retroperitoneum is also characteristic.<br />Therapy and survival rates: <br />         When possible, surgical resection remains the preferred treatment for gastric adenocarcinoma (5-year survival rate of early gastric cancer can exceed 90%)<br />         The 5-year survival rate for advanced gastric cancer remains below 20%. Because of the advanced stage at which most gastric cancers are discovered in the United States, the overall 5-year survival is less than 30%.<br />o   In such cases efforts are usually focused on chemotherapy or radiation therapy and palliative care.<br />CHRONIC GASTRITIS<br />Definition: Chronic inflammation of the stomach mucosa. <br />         In contrast to acute gastritis, the symptoms associated with chronic gastritis are typically less severe but more persistent. <br />         Nausea and upper abdominal discomfort may occur, sometimes with vomiting, but hematemesis is uncommon. <br />         The most common cause of chronic gastritis is infection with the bacillus Helicobacter pylori. <br />         Autoimmune gastritis, the most common cause of atrophic gastritis, represents less than 10% of cases of chronic gastritis and is the most common form of chronic gastritis in patients without H. pylori infection.<br />         Less common etiologies include radiation injury, chronic bile reflux, mechanical injury, and involvement by systemic disease such as Crohn disease, amyloidosis, or graft-versus-host disease.<br />Pathogenesis: <br />         H. pylori infection is the most common cause of chronic gastritis. <br />         The disease most often presents as a predominantly antral gastritis with high acid production, despite hypogastrinemia. <br />         The risk of duodenal ulcer is increased in these patients and, in most; gastritis is limited to the antrum with occasional involvement of the cardia. <br />         In a subset of patients the gastritis progresses to involve the gastric body and fundus. This pangastritis is associated with multifocal mucosal atrophy, reduced acid secretion, intestinal metaplasia, and increased risk of gastric adenocarcinoma.<br />         H. pylori organisms have adapted to the ecologic niche provided by gastric mucus. Although H. pylori may invade the gastric mucosa, this is not evident histologically and the contribution of invasion to disease is not known. Four features are linked to H. pylori virulence:<br />1.       Flagella, which allow the bacteria to be motile in viscous mucus2.       Urease, which generates ammonia from endogenous urea and thereby elevates local gastric pH3.       Adhesins that enhance their bacterial adherence to surface foveolar cells4.       Toxins, such as cytotoxin-associated gene A (CagA), that may be involved in ulcer or cancer development by poorly defined mechanisms<br />         Although the mechanisms by which H. pylori cause gastritis are incompletely defined, it is clear that infection results in increased acid production and disruption of normal gastric and duodenal protective mechanisms, as described earlier. <br />         H. pylori gastritis is, therefore, the result of an imbalance between gastroduodenal mucosal defenses and damaging forces that overcome those defenses.<br />Morphology- Gross: Gastric biopsy specimens generally demonstrate H. pylori in infected individuals. <br />         The organism is concentrated within the superficial mucus overlying epithelial cells in the surface and neck regions. <br />         Within the stomach, H. pylori are typically found in the antrum. <br />o   Antral biopsy is preferred for evaluation of H. pylori gastritis. <br />         H. pylori–infected antral mucosa is usually erythematous and has a coarse or even nodular appearance. <br />Morphology-Microscopy: <br />         Gastric biopsy specimens generally demonstrate H. pylori in infected individuals. <br />         The organism is concentrated within the superficial mucus overlying epithelial cells in the surface and neck regions. <br />         The distribution can be irregular, with areas of heavy colonization adjacent to those with few organisms. In extreme cases, the organisms carpet the luminal surfaces of foveolar and mucous neck cells, and can even extend into the gastric pits. <br />         Organisms are most easily demonstrated with a variety of special stains. <br />         H. pylori shows tropism for gastric epithelia and is generally not found in association with gastric intestinal metaplasia or duodenal epithelium. However, H. pylori may be present in foci of pyloric metaplasia within chronically injured duodenum or gastric-type mucosa within Barrett esophagus.<br />         Within the stomach, H. pylori are typically found in the antrum (as previously said). <br />         H. pylori are uncommon in oxyntic (acid-producing) mucosa of the fundus and body except in heavy colonization. <br />         When viewed endoscopically, H. pylori-infected antral mucosa is usually erythematous and has a coarse or even nodular appearance. The inflammatory infiltrate generally includes variable numbers of neutrophils within the lamina propria, including some that cross the basement membrane to assume an intraepithelial location and accumulate in the lumen of gastric pits to create pit abscesses.<br />         In addition, the superficial lamina propria includes large numbers of plasma cells, often in clusters or sheets, and increased numbers of lymphocytes and macrophages. <br />         Intraepithelial neutrophils and subepithelial plasma cells are characteristic of H. pylori gastritis. <br />         When intense, inflammatory infiltrates may create thickened rugal folds, mimicking early infiltrative lesions. <br />Important: Long-standing H. pylori gastritis may extend to involve the body and fundus, and the mucosa can become atrophic. Lymphoid aggregates, some with germinal centers, are frequently present and represent an induced form of mucosa-associated lymphoid tissue, or MALT, that has the potential to transform into lymphoma.<br />Therapy: Triple therapy initially (Amoxicillin, Clarithomycin, Omeprazole) <br />         H+ and proton pump inhibitor drugs <br />         Antacids<br />ADDITIONAL PATHOLOGICAL CONDITIONS AFFECTING GASTRIC MUCOSA <br />AUTOIMMUNE GASTRITIS -PERNICIOUS ANEMIA<br /> <br />Definition: Pernicious anemia (PA) is an organ-specific autoimmune disease characterized by chronic inflammation of the fundus and body of the stomach, and loss of gastric parietal cells.<br />Pathogenesis: <br />         Patients with PA develop achlorhydria, decreased production of pepsinogen 1, and decreased production of intrinsic factor. <br />         The decrease in intrinsic factor, in combination with antibodies that block intrinsic factor function, leads to vitamin B12 (cobalamin) malabsorption and its consequences -megaloblastic anemia and neuropathy.<br />         The chronic gastritis associated with PA has been called type A gastritis, which is distinguished by the fact that the inflammation spares the antrum of the stomach and thus is associated with gastric gland hyperplasia (due to lack of negative feedback by gastric acid) and elevated serum gastrin levels. <br />         Type A gastritis differs from type B gastritis in that the latter involves the entire stomach and is associated with low serum gastrin levels. As discussed in the following section, this form of gastritis is due to chronic infection with H pylori.<br />Epidemiology: PA usually occurs in older individuals (usually women) and may be part of a polyendocrine autoimmune state involving the thyroid gland (Hashimoto's thyroiditis), the adrenal gland (Addison's disease), or the islet cells (juvenile diabetes melitis). <br />Immunologic Pathogenesis:<br />         It has been known for quite some time that PA is associated with the presence of antibodies to parietal cells, and it was assumed that such antibodies were the cause of the inflammation. <br />         Another hypothesis concerning the pathogenesis of PA comes from studies of mouse models of gastritis in which it can be shown that CD4 T cells (also specific for H+/K+-ATPase) can transfer gastritis to naive recipients. <br />         Thus, it appears that CD4 T cells are the chief effectors of gastritis in mice, and, by extension, in human gastritis and PA. <br />Morphology-Gross:<br />         Autoimmune gastritis is characterized by diffuse mucosal damage of the oxyntic (acid-producing) mucosa within the body and fundus. <br />         Damage to the antrum and cardia is typically absent or mild. <br />         With diffuse atrophy, the oxyntic mucosa of the body and fundus appears markedly thinned, and rugal folds are lost. <br />         If vitamin B12 deficiency is severe, nuclear enlargement (megaloblastic change) occurs within epithelial cells. <br />Morphology- Microscopic: <br />         Inflammatory infiltrate is composed of lymphocytes, macrophages, and plasma cells. <br />         Lymphoid aggregates may be present. <br />         The superficial lamina propria plasma cells of H. pylori gastritis are typically absent, and the inflammatory reaction is most often deep and centered on the gastric glands). <br />         Loss of parietal and chief cells can be extensive. When atrophy is incomplete residual islands of oxyntic mucosa may give the appearance of multiple small polyps or nodules. <br />         Small surface elevations may be apparent, and these correlate with areas of intestinal metaplasia, characterized by the presence of goblet cells and columnar absorptive cells. <br />         The antral endocrine cell hyperplasia that develops in most patients can be difficult to appreciate on H&E-stained sections, since the endocrine cells, which are also referred to as enterochromaffin-like (ECL) cells, are not easily recognized. <br />         This hyperplasia parallels the degree of mucosal atrophy and is a physiologic response to decreased acid production. <br />         Over time, hypergastrinemia can stimulate endocrine cell hyperplasia in the fundus and body. Rarely, this may progress to form small, multicentric, low-grade neuroendocrine, or carcinoid, tumors.<br />Diagnosis: The diagnosis of PA is made on the basis of the histologic picture described here and the presence of an abnormal Schilling's test for the detection of vitamin B12 malabsorption. <br />         The latter consists of the administration of radiolabeled vitamin B12 by mouth, followed by measurement of the uptake of the label and its appearance in the stool. <br />         Reduced uptake and increased excretion of the labeled vitamin B12 indicates the presence of PA. <br />         Characteristically, the Schilling's test "corrects" if labeled vitamin B12 is coadministered with exogenous intrinsic factor. <br />Shilling test: <br />         The Schilling test has multiple stages<br />Stage 1: Oral vitamin B12 plus intramuscular vitamin B12<br />         In the first part of the test, the patient is given radiolabeled vitamin B12 to drink or eat. <br />         An intramuscular injection of unlabeled vitamin B12 is given at or around the same time. <br />         This is not enough to replete or saturate body stores of B12 (this requires about 10 B12 injections over some length of time). <br />         The purpose of the single injection is to temporarily saturate B12 receptors in the liver with enough normal vitamin B12 to prevent radioactive vitamin B12 binding in body tissues (especially in the liver), so that if absorbed from the G.I. tract, it will pass into the urine. <br />         The patient's urine is then collected over the next 24 hours to assess the absorption.<br />         Normally: the ingested radiolabeled vitamin B12 will be absorbed into the body. <br />o   Since the body already has liver receptors for transcobalamin/vitamin B12 saturated by the injection, much of the ingested vitamin B12 will be excreted in the urine.<br />o   A normal result shows at least 5% of the radiolabeled vitamin B12 in the urine over the first 24 hours. <br />         In patients with pernicious anemia or with deficiency due to impaired absorption: less than 5% of the radiolabeled vitamin B12 is detected. <br />Stage 2: vitamin B12 and intrinsic factor<br />         If an abnormality is found, the test is repeated, this time with additional oral intrinsic factor.<br />         If this second urine collection is normal, this shows a lack of intrinsic factor production, or pernicious anemia. <br />         A low result on the second test implies abnormal intestinal absorption (malabsorption), which could be caused by coeliac disease, biliary disease, Whipple's disease, fish tapeworm infestation (Diphyllobothrium latum), or liver disease. <br />         Malabsorption of B12 can be caused by intestinal dysfunction from a low vitamin level in-and-of-itself (see below), causing test result confusion if repletion has not been done for some days previously. <br /> Stage 3: vitamin B12 and antibiotics: This stage is useful for identifying patients with bacterial overgrowth syndrome.<br />Stage 4: vitamin B12 and pancreatic enzymes: This stage, in which pancreatic enzymes are administered, can be useful in identifying patients with pancreatitis.<br />Treatment:Treatment of PA consists of parenteral vitamin B12 injection. <br /> <br /> <br />INFLAMATORY AND HYPERPLASTIC POLYPS IN THE STOMACH <br /> <br />Epidemiology: <br />         Polyps, nodules or masses that project above the level of the surrounding mucosa, are identified in up to 5% of upper GI endoscopies. <br />         Polyps may develop as a result of epithelial or stromal cell hyperplasia, inflammation, ectopia, or neoplasia.      <br />         Approximately 75% of all gastric polyps are inflammatory or hyperplastic polyps. <br />         They are most common in individuals between 50 and 60 years of age. <br />         These polyps usually develop in association with chronic gastritis, which initiates the injury and reactive hyperplasia that leads to polyp growth.<br />Morphology- Gross: <br />         Majority of inflammatory or hyperplastic polyps are smaller than 1 cm in diameter and are frequently multiple, particularly in individuals with atrophic gastritis. <br />         These polyps are ovoid in shape and have a smooth surface, though superficial erosions are common. <br />Morphology: Microscopy: <br />         Microscopically, polyps have irregular, cystically dilated, and elongated foveolar glands.<br />FUNDIC GLAND POLYPS <br />Epidemiology: <br />         Fundic gland polyps occur sporadically and in individuals with familial adenomatous polyposis (FAP). <br />         The prevalence of fundic gland polyps has increased markedly in recent years as a result of proton pump inhibitor therapy. <br />         This likely reflects increased gastrin secretion, in response to reduced gastric acidity, and the resulting glandular hyperplasia. <br />         These polyps are five times more common in women and are discovered at an average age of 50 years.<br />         Fundic gland polyps may be asymptomatic or associated with nausea, vomiting, or epigastric pain.<br />Morphology: <br />         Fundic gland polyps occur in the gastric body and fundus and are well-circumscribed lesions with a smooth surface. <br />         They may be single or multiple and are composed of cystically dilated, irregular glands lined by flattened parietal and chief cells. Inflammation is typically absent or minimal.<br /> <br />GASTRIC ADENOMAS<br />Epidemiology: <br />         Gastric adenomas represent as many as 10% of all gastric polyps. <br />         Their incidence increases progressively with age, and there is a marked variation in rate among different populations that parallels the incidence of gastric adenocarcinoma. <br />         Patients are usually between 50 and 60 years of age, and males are affected three times more often than females.<br />         Like fundic gland polyps, the incidence of adenomas is increased in individuals with FAP. Similar to other forms of gastric dysplasia, adenomas almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia.<br />         The risk of adenocarcinoma in gastric adenomas is related to the size of the lesion and is particularly elevated in lesions greater than 2 cm in diameter. <br />         Overall, carcinoma may be present in up to 30% of gastric adenomas<br />Morphology-Gross: Gastric adenomas are usually solitary lesions less than 2 cm in diameter, most commonly located in the antrum. <br />Morphology-Microscopic: The majority of adenomas are composed of intestinal-type columnar epithelium. <br />         By definition, all GI adenomas have epithelial dysplasia that can be classified as low or high grade. <br />         Both grades may include enlargement, elongation, and hyperchromasia of epithelial cell nuclei, epithelial crowding, and pseudostratification. <br />         High-grade dysplasia is characterized by more severe cytologic atypia and irregular architecture, including glandular budding and gland-within-gland, or cribriform, structures<br /> <br />1. <br />A 33 year old male was examined in the local physician’s office. He presents with paresthesia (loss of tactile sensation) and visual hallucinations. Blood work reveals a presence of megaloblastic anemia (as seen in the picture). Endoscopy of the upper GI tract identifies the presence of mucosal atrophy in the stomach. Patient was diagnosed with pernicious anemia. What is the most likely cause of this patient’s neurological and hematological problems? <br />Top of Form<br />Impaired absorption of vitamin B12 Impaired absorption of vitamin B6Impaired absorption of iron Increased absorption of copper<br />Bottom of Form<br />2. <br />What is the most common cause of chronic gastritis? <br />Top of Form<br />Smoking Presence of aflatoxin in the foodAlcohol consumptionCandida infection H. Pylori infection<br />Bottom of Form<br />3. <br />During the autopsy of a 55 year old male, pathologist notes a presence of a single large polypoid structure in the wall of the stomach (see the image). Histological examination reveals a presence of intestinal-type columnar epithelium embedded in the normal stroma of the stomach (see the second image). There are no signs of cellular atypia and malignant transformation. What is the most likely diagnosis in this patient?<br />Top of Form<br />Metenier’s diseasePernicious anemiaGastric adenocarcinoma Gastric adenoma <br />Bottom of Form<br />4. <br />A 65 year old Japanese male presents with a progressive loss of weight, dysphagia, and gastric pain. He also noticed a presence of blood in the stool. Endoscopy confirms the presence of the ulcerated mass that has raised edges. The bleeding was also confirmed. Histological examination of biopsied material shows a presence of dicohesive atypical cells that contain large mucin vacuoles that expand the cytoplasm and push the nucleus to the periphery (Signet cells, see the image). What is the most likely cause of these patients’ problems?<br />Top of Form<br />Pernicious anemia Peptic ulcer Gastric atrophyChronic gastritis Gastric adenocarcinoma<br />Bottom of Form<br />5. <br />Which of the following factors is involved in the pathogenesis of pernicious anemia?<br />Top of Form<br />Autoimmune destruction of chief cells in the stomach Loss of mynteric plexus in the wall of the stomach Autoimmune destruction of parietal cells in the stomach Hypertrophy of the mucous cells in the stomach <br />Bottom of Form<br /> <br />Review Options   <br />Top of Form<br />Bottom of Form<br />          <br />