Cardia: narrow conical portion distal to gastroesophageal junction; many authors claim that cardiac mucosa is reflux-associated epithelia and not normally present

Fundus: dome shaped proximal stomach

Body/corpus: remainder of stomach to incisura angularis

Incisura angularis: where stomach narrows before it joins duodenum

Antrum: incisura angularis to pyloric sphincter (3-4 cm)

Pylorus: muscular ring that controls flow of food content into proximal duodenum

Lesser curvature: medial curvature of stomach

Greater curvature: lateral curvature of stomach

Normal histology

Layers: mucosa, submucosa (with Meisner plexus), muscularis propria (outer longitudinal layer, Auerbach/myenteric plexus, inner circular layer, innermost oblique layer), serosa

Mucosal components: foveola (surface epithelium and deeper crypts/pits) and underlying secretory glands

Mucous neck cells: at base of foveola, progenitors of surface epithelium and gastric glands, mitotically active, site of gastric carcinogenesis

Ratio of foveola to gland volume differs by region: cardia/antrum: 50/50; fundus: 25/75

Cardia: branching mucous glands without parietal cells; may have cysts within glands; variable length of 0 to 15 mm; may be metaplastic epithelium due to reflux, AJSP 2002;26:1207, AJSP 2002;26:1032, AJSP 2001;25:1188, AJSP 2000;24:402, AJSP 2000;24:344, Archives 2003;127:451

Fundus: aka oxyntic mucosa; straight glands composed of tightly packed chief cells, parietal cells, endocrine cells, mucus cells; higher ratio of glands to foveola than antrum; region of fundic mucosa shrinks with age (termed pyloric metaplasia)

Antrum: branching mucus glands, cytoplasm may be bubbly, vacuolated, granular or glassy; often ciliated in Japanese patients (Japan J Cancer Res. 1986;77:282, case report in American patient at AJSP 1988;12:786); may contain small aggregates of lymphocytes without germinal centers

Parietal cells: primarily in fundus/body; eosinophilic due to abundant mitochondria, produce acid via H+/K+ ATPase pump; also secrete intrinsic factor which binds luminal Vitamin B12

Stimulated by vagus nerve, binding of gastrin receptor by gastrin from antral cells, binding of H2 receptor by histamine from enterochromaffin-like cells

Chief cells: fundus/body; basophilic cytoplasm due to abundant rough endoplasmic reticulum; release pepsinogen I and II, which are activated by low luminal pH to pepsin

Endocrine cells: scattered in fundus/body (produce histamine, are enterochromaffin-like), more prominent in antral glands; produce gastrin (G cells), serotonin (enterochromaffin cells), somatostatin (D cells); often have clear cytoplasm

Enterochromaffin-like (ECL) cells: non-peptide secreting endocrine cell of gastric fundus/body mucosa; represent 30% of endocrine cells; release histamine in response to gastrin produce by G cells; long term gastrin stimulation causes ECL hyperplasia

Mucous cells: produce neutral (PAS positive) mucin, usually not acidic mucins; lightly eosinophilic or clear cytoplasm and bubbly

Negative stains: CDX2 (except in areas of intestinal metaplasia)

Mucosal protection against autodigestion

(a) mucus secretion: mucus is relatively impermeable to H+; also fluid with acid or pepsin exits gastric glands as “jets” and penetrates surface mucus layer without contacting surface epithelial cells

(b) bicarbonate secretion creates pH neutral microenvironment adjacent to cell surface

(d) rich blood flow supplies bicarbonate and nutrients and removes acid

(e) muscularis mucosa limits injury; if intact, repair occurs in hours/days vs. weeks if not intact

Non-neoplastic anomalies

Achalasia of cardia

Rare disorder of children

Due to defective relaxation of the cardia and absence of peristalsis in esophageal body

May occur as part of Allgrove’s syndrome (triple A syndrome, OMIM 231550), an autosomal recessive disorder which features achalasia, addisonianism (ACTH insensitivity), and alacrima (lack of tears), and may have late-onset progressive neurologic symptoms; disease may be due to mutations of Aladin (Adracalin) gene at 12q13

Associated with lack of nitrous oxide nerve fibers and with lymphocytes infiltrating myenteric plexus

Micro: fibrosis between circular and longitudinal muscles, reduction in myenteric ganglia and myenteric neurons

References: AJSP 2003;27:667

Arteriovenous malformation

Rare, case report of incidental finding with amyloid deposits at autopsy in 74 year old man, Archives 1986;110:69

Diaphragmatic hernia

Defective closure of diaphragm, usually left sided

Hernia sac usually contains all/part of stomach

May cause newborn respiratory insufficiency

Gastric dilation

Due to gastric outlet obstruction or paralytic ileus

Stomach may contain 10 L of fluid, rarely ruptures

Newborns rarely have spontaneously perforation due to labor and delivery, severe vomiting, CPR

Gastric gland heterotopia

Aka gastric adenomyoma

Hamartoma of stomach composed of large ducts, Brunner’s glands, prominent smooth muscle bundles

May produce peptic type ulcers in duodenum and bleeding

Heterotopic pancreas / pancreatic acinar metaplasia

Nodules of normal pancreatic tissue up to 1 cm in gastric or intestinal wall

Prevalence 1-2%; incidental or presents as mass; in 4% of pediatric gastric biopsies, AJSP 1998;22:100

Usually antrum or pylorus; when in pylorus, localized inflammation may cause obstruction

Strongly associated with chronic gastritis and intestinal metaplasia, but not H. pylori infection

At GE junction in children/young adults, but may also be congenital, Archives 2000;124:1165, AJSP 1996;20:1507

Case reports with mucus retention simulating mucinous carcinoma, AJSP 1994;18:953, with pancreatic adenocarcinoma at GE junction, Archives 1994;118:568

Gross: nipple-like projection (with duct emptying into gastric lumen), symmetric cone or round mass; cut surface resembles normal pancreas, but may be cystic

Micro: pancreatic acini and ducts usually present (total heterotopia), ducts often dilated, islets present in 30%; rarely endocrine only (case report at Archives 2002;126:464); may have mucocele-like changes; usually in submucosa or muscularis propria

Positive stains: lipase, trypsinogen, amylase

References: AJSP 1993;17:1134

Mucolipidosis

Mucolipidosis type IV: autosomal recessive lysosomal storage disease, causes severe neurologic abnormalities

In brain, have accumulation of lamellated membrane structures in lysosomes and pigmented cytoplasmic granules in neurons

In stomach, associated with hypergastrinemia, achlorhydria, chronic atrophic gastritis, enterochromaffin-like cell hyperplasia; parietal cells have striking cytoplasmic vacuolization, due to large lysosomes containing lamellar, concentric, and cystic membranous inclusions

References: AJSP 1999;23:1527

Pyloric stenosis

Congenital or acquired

Congenital

Common congenital abnormality (1 per 300-900 births)

75% are male, onset at 3-12 weeks, high concordance in monozygotic twins, associated with Turner’s syndrome, trisomy 18, esophageal atresia

Symptoms: persistent projectile non-bilious vomiting in second week of life; regurgitation; visible peristalsis

Gross: thickened pyloric muscle resembling a fusiform mass, 3-5 cm, that occludes the pyloric channel

Micro: edema and inflammatory changes in mucosa or submucosa; thickening primarily of circular muscle, which terminates abruptly distally

Treatment: pyloromyotomy (split pyloric muscle)

Acquired

80% in men, hypertrophy of pyloric circular muscle fibers that ends at duodenum

Associated with antral gastritis or pyloric ulcer

DD: linitis plastica adenocarcinoma

Gastritis

Features to report

Sydney system

Biopsies

Recommended to take 5 biopsy specimens, 2 from antrum (both at 2 to 3 cm from the pylorus, 1 from lesser and 1 from greater curvature), 2 from corpus (both at 8 cm from the cardia, from lesser and greater curvature), 1 from the incisura angularis; all samples should be identified and studied separately; 5 biopsies appears to be adequate, although site is often misidentified, Hum Path 2003;34:28

Low concordance rate between pathologists improves after joint review of cases, Hum Path 1999;30:1431

Report:
Location of gastritis (antrum, fundus/body, cardia, diffuse)

Type of gastritis: active, chronic or other (lymphocytic, granulomatous, eosinophilic, etc.)

Grade the presence of Helicobacter pylori, chronic inflammation, active inflammation, glandular atrophy, intestinal metaplasia

Report (ungraded) granulomas, eosinophils, intraepithelial lymphocytes

Alternative reporting:

Antral predominant, corpus predominant or pangastritis

Focal or diffuse

Superficial or full thickness

Atrophy: present or absent

Metaplasia: present or absent

Inflammation: active, chronic or both

H. pylori present or absent

Active gastritis

Acute mucosal inflammatory process, usually transient (normal stomach has only rare inflammatory cells)

May be accompanied by local hemorrhage or mucosal sloughing

Severe erosive disease may cause acute GI bleeds

Associated with heavy use of NSAIDs (non-steroidal anti-inflammatory drugs, including aspirin), excessive alcohol use, heavy smoking, cancer chemotherapy, bile reflux, uremia, systemic infections (Salmonella), severe stress (trauma, burns, surgery), ischemia and shock, acid/alkali ingestion as part of suicide attempts, gastric irradiation or freezing, mechanical trauma (nasogastric tube), distal gastrectomy

Major cause of massive hematemesis in alcoholics

Occurs in 25% of those who take daily aspirin for rheumatoid arthritis

Symptoms: none, or pain, nausea and vomiting

Physiology: mucosal damage due to increased acid secretion, decreased bicarbonate buffer, reduced blood flow, disruption of mucous layer

Micro: mild: modest edema of lamina propria, slight vascular congestion, intact epithelium, scattered neutrophils; severe: erosion and hemorrhage in mucosa

Erosion: loss of superficial epithelium above muscularis mucosa, accompanied by robust acute inflammatory infiltrate and extrusion of a fibrinopurulent exudate into the lumen

Allergic gastroenteritis

Usually children with vomiting, diarrhea and growth failure; also allergic history, anemia, blood eosinophilia, increased serum IgE

Treatment: steroids, but may have multiple relapses

Micro: diffuse and marked eosinophils in mucosa of antrum, focally in fundus/body

References: AJSP 1986;10:75

Autoimmune gastritis

Aka type A gastritis

< 10% of cases of chronic gastritis

Associated with hypochlorhydria or achlorhydria (due to severe parietal cell loss), high serum gastric levels, but usually no symptoms

90% have anti-parietal cell antibodies, 60% have anti-intrinsic factor antibodies; use rat stomach/kidney blocks for parietal cell staining and to rule out renal tubular staining

Anti-parietal cell antibodies are to the proton pump (potassium / hydrogen ATPase)

Often autosomal dominant

Associated with other autoimmune diseases (Hashimoto’s thyroiditis, Addison’s disease) but NOT with Helicobacter pylori gastritis

Occasionally leads to pernicious anemia (due to loss of intrinsic factor), indolent carcinoid tumors

Intrinsic factor: type 1 intrinsic factor antibody prevents binding of intrinsic factor to Vitamin B12; type 2 antibody reacts with free or complexed Vitamin B12 to prevent its biological activity

Micro: glandular atrophy predominantly in gastric body/fundus with deep or diffuse lymphoplasmacytic infiltrates within lamina propria and focal gland infiltration and damage; 85% have parietal cell pseudohypertrophy with snouting; often extensive intestinal, antral or pancreatic acinar metaplasia; linear or nodular neuroendocrine (enterochromaffin cell-like/ECL) hyperplasia on chromogranin immunostains; no/rare H. pylori

References: Mod Path 2002;15:102

Carditis

Common finding: present in 75-95% of biopsies; intestinal metaplasia present in 10-22% of unselected patients

Eosinophils in cardia are associated with active esophagitis (GERD)

Marked lymphocytic inflammation without eosinophils is associated with chronic gastritis and H. pylori infection

Goblet cells are associated with both GERD and H. pylori infection; don’t call Barrett’s esophagus based only on cardia findings, Mod Path 1999;12:1017

Most (79%) cases of carditis have no gastritis in antrum

Acute inflammation present in 18% (12% in low grade carditis, 57% in severe carditis), predicts associated distal gastritis and H. pylori infection

References: AJSP 2002;26:1032, AJSP 2001;25:245

Crohn’s disease

Clinical involvement is rare, although microscopic evidence of disease is more common

50% of gastric granulomas are due to Crohn’s disease

Focal acute inflammation in a background of non-inflamed, H. pylori negative mucosa is suggestive of Crohn’s disease, AJSP 1998;22:383

Acute inflammation present in 56%, but only 10% were H. pylori positive

Granulomas present in only 9%

DD (granulomas): tuberculosis, fungus, Whipple’s disease, foreign-body, sarcoid, tumor, granulomatous gastritis

Chronic gastritis

Chronic mucosal inflammatory changes leading to mucosal atrophy and epithelial metaplasia, usually without erosions

Most cases are type B or non-autoimmune gastritis

Associated with chronic Helicobacter pylori infection, toxins (alcohol, tobacco), reflux of bilious duodenal secretions (post-antrectomy or other), obstruction (bezoars, atony), radiation

Increases with age; in Europe/Japan, affects 50% at age 60+

Histology does not correlate well with symptoms

Superficial chronic gastritis: inflammation confined largely to mucosa occupied by gastric pits

Micro: plasma cells, lymphocytes, occasional lymphoid follicles; may have eosinophils and neutrophils also; may have reduced cytoplasmic mucin, reactive epithelial changes (nuclear and nucleolar enlargement)

May have subnuclear vacuolation in antral glands or pits (PAS negative), probably represents degenerative response to cell injury

Intestinal metaplasia: affects antral and body/fundic mucosa, with partial replacement by metaplastic goblet cells of intestinal morphology, absorptive cells and Paneth cells; extensive if involves 25% of biopsy tissue

Immunophenotypically distinct from intestinal metaplasia of GE junction or Barrett’s esophagus, AJSP 2001;25:87

Complete intestinal metaplasia: mucosal pattern resembles small bowel epithelium with goblet and absorptive cells, villi and crypts; sialomucins predominate

Incomplete intestinal metaplasia: no absorptive cells, columnar cells resemble gastric foveolar cells; neutral mucins and sulfomucins are present

Chronic atrophic gastritis

Chronic gastritis accompanied by glandular atrophy (mild, moderate, severe), usually secondary to chronic H. pylori infection; initially glands are compressed, later they are destroyed, and conditions become inhibitory to bacterial growth

Associated with duodenal ulcer, gastric peptic ulcer

Degree of atrophy and intestinal metaplasia are correlated, Hum Path 2001;32:31

Epithelial changes may become dysplastic and progress to carcinoma

Metaplastic atrophic gastritis of environmental type: involvement of 25%+ of antral surface and glandular epithelium by intestinal metaplasia

Gross: thin, smooth mucosa (without rugae), prominent submucosal vessels (due to mucosal atrophy)

Collagenous gastritis

Very rare, <25 cases reported

Children and young adults with severe anemia, nodular endoscopic pattern

Associated with collagenous colitis in adults with chronic watery diarrhea or with celiac disease

Case reports in patients with celiac disease, Archives 2001;125:1579, Mod Path 2000;13:591

Endoscopy: erosion and hemorrhages in children

Micro: thick subepithelial collagen band (at least 10 microns, mean 30 microns, normal is 1 micron), often ragged at lower edge, commonly with entrapped red blood cells, fibroblasts, inflammatory cells and superficial capillaries; associated with mixed inflammatory infiltrate of lamina propria and variable surface epithelial damage of cuboidal cytoplasmic changes, reactive cytoplasmic changes, reactive nuclear enlargement, subepithelial edema and erosions

References: AJSP 2001;25:1174

Eosinophilic gastroenteritis

Aka diffuse eosinophilic gastroenteritis

Involves distal stomach, proximal duodenum; may cause pyloric obstruction; often middle aged women

Usually idiopathic; associated with allergies (cow’s milk or soy protein in infants), peripheral eosinophilia in 75%, infestation by Eustoma rotundatum (North Sea herring parasite), anisakiasis, collagen vascular disease (scleroderma, polymyositis)

Treatment: corticosteroids

Micro: diffuse, sheet like, monomorphic infiltration of eosinophils, may be transmural; also variable edema, necrotizing angiitis

DD: inflammatory fibroid polyp, lymphoma, carcinoma

Erosive gastritis

Erosion: ulcer that has not penetrated the muscularis mucosa

Acute hemorrhagic gastritis: multiple erosions in diffusely hemorrhagic mucosa, causes up to 25% of hospital admissions for acute upper GI bleed, may require emergency gastrectomy; base of erosions may have necrotic tissue overlying normal epithelium, capillary congestion at edges of erosion

Focal erosions in otherwise normal mucosa: may ooze blood and cause anemia, but usually are asymptomatic

Causes: alcohol, aspirin, NSAIDs, shock, sepsis, hypoxia, nasogastric tubes (similar to acute ulcer)

Granulomatous gastritis

Causes: anisakiasis, common variable immunodeficiency, Crohn’s disease, foreign body, histoplasmosis, idiopathic, post-barium studies, sarcoidosis, tuberculosis, tumors, vasculitis; rarely Langerhans cell histiocytosis

Idiopathic / isolated: usually older white men vs. sarcoid (young black men/women)

Chronic granulomatous disease: may present with distinct or poorly formed granulomas in children with pigment-laded macrophages; associated with outlet obstruction, AJSP 1982;6:673

Graft versus host disease

Common after allogeneic bone marrow transplantation, although diagnosis based on subtle findings

Similar histology associated with common variable immunodeficiency and X-linked agammaglobulinemia, AJSP 1996;20:1240

Micro: apoptosis, gland destruction, sparse inflammatory infiltrate, granular eosinophilic debris in dilated glands (“exploding crypt cell”, 94% specific, 41% sensitive)

DD: CMV, HIV

Reference: AJSP 1997;21:1037

Hemorrhagic gastritis

Acute, life threatening, 55% mortality

Arises in background of chronic gastritis

Causes: stress, alcohol, NSAIDs

Treatment: vagotomy, subtotal gastrectomy

Gross: multiple hemorrhagic areas in gastric mucosa

Micro: multiple superficial erosions, chronic atrophic gastritis; less dramatic than gross observations

Ischemic gastritis

Rare due to richness of gastric blood supply

May have erosions and ulcers due to ischemia, secondary to emboli

Usually antral, irregular in shape; adjacent mucosa often has multiple erosions

Lymphocytic gastritis

Uncommon, characterized by lymphocytosis of foveolar and surface epithelium (25+ lymphocytes per 100 surface epithelial cells) and chronic inflammation in lamina propria

First described in 1988, Gut 1988;29:1258

Associated with celiac disease (present in 1/3 of these patients, both have similar severity in children, AJSP 1996;20:865), rarely with Helicobacter pylori (HP) gastritis (present in 4% of these patients); less commonly with Crohn’s disease, HIV, lymphoma, esophageal carcinoma, inflammatory polyp

High number of granzyme B positive (activated cytotoxic) T cells in nonceliac disease-associated lymphocytic gastritis, AJSP 1998;22:450

Treatment: treat underlying celiac disease or H. pylori infection

Endoscopy: normal (low grade) or nodules, erosions and large folds (more severe disease, aka varioliform gastritis); most severe form may resemble Menetrier’s disease

Gross: antral (celiac disease) or corpus (H. pylori infection) involvement

Micro: increased lymphocytes in surface and foveolar epithelium, as well as lamina propria; 25+ lymphocytes per 100 epithelial cells is minimum; most cases have 30-65 lymphocytes/100 epithelial cells; lymphocytes are small and round without atypia, most are T cells; may have clear halo (artifact); lymphoepithelial lesions are rare, no active gland destruction

Lymphocytes most numerous in varioliform gastritis (large folds due to foveolar hyperplasia, not considered Menetrier’s disease)

DD: MALT lymphoma (expanded lamina propria, dense collection of monocytoid cells larger than small lymphocytes, may be plasmacytoid, have Dutcher bodies; also intraepithelial lymphocytes, infiltration of muscularis mucosa; lymphoepithelial lesions usually contain 3+ cells; often active gland destruction; B cell origin vs. T cell for lymphocytic gastritis)

References: AJSP 1999;23:153

Malakoplakia

Case report associated with gastric adenocarcinoma, Archives 1978;102:136

Gross: slightly elevated plaque with umbilication of overlying mucosa

Micro: submucosal histiocytes with cytoplasmic inclusions (Michaelis-Gutmann bodies)

EM: inclusions have dense central calcified body and concentric alternating rings

Pseudomembranous gastritis

Case report of post-BMT man with GVHD and Aspergillus infection, Archives 2000;124:619

Pseudomembranes also caused by chronic erosions, ischemia

Gross (case report): gastric mucosa covered by 1.5 cm thick pseudomembrane containing Aspergillus, with friable yellow mucoid material and multiple hemorrhagic foci

Micro (case report): fibrin, mucus, neutrophils, fungal hyphae with acute angle branching consistent with Aspergillus; distended gastric glands extended to pseudomembrane in volcano-like appearance; hemorrhagic necrosis common with “ghost” (necrotic) gastric glands

Positive stains (case report): GMS

Reactive (chemical) gastropathy

Aka reflux gastritis, type C gastritis

Second most common diagnosis for gastric biopsies in North America

Associated with gastrectomy, bile reflux, gastroesophageal reflux disease, drug therapy (NSAIDs - 34-45%)

Due to increased surface cell exfoliation

Usually diffuse (present on more than one biopsy)

Micro: (a) prominent foveolar hyperplasia, (b) fibromuscular replacement of the lamina propria, (c) lamina propria edema, (d) vascular dilation/congestion of superficial mucosal capillaries, (e) paucity of active and chronic inflammatory cells; can grade each feature on 0-3 scale to provide reflux score (maximum 15, 10+ indicates reactive gastropathy); glandular compartment unchanged; foveolar cell vacuolization associated with bile reflux, AJSP 1988;12:773

Foveolar hyperplasia: corkscrew appearance of superficial mucosa with loss of cytoplasmic mucus, nuclear enlargement and hyperchromasia; most useful feature for diagnosis since easiest to assess

Suppurative

Bacterial cellulitis primarily affecting submucosal layer of stomach

Usually caused by Strep Group A, also Staph, E. coli, H. influenza

Rigors, fever, high death rate

Emphysematous gastritis: associated with gas forming organisms

Predisposing factors: alcoholism, chronic renal failure, immunodeficiency, hypochlorhydria, endoscopic polypectomy

Gross: distention of stomach with marked thickening of wall due to edema

Micro: submucosal edema, congestion, hemorrhage; massive neutrophilic exudate with bacteria; overlying mucosa may be unremarkable

Ulcerative colitis

Rare; variable changes include multiple tiny shallowulcers, crypt abscess formation, increased intraepithelial lymphocytes, villous blunting

Microscopic findings parallel remissions and relapses of colonic inflammation

Infections

Anthrax

Most severe and most rare form of anthrax

Due to ingesting raw meat/milk from infected animals; only occurs in underdeveloped regions

Death due to marked fluid/blood loss from GI tract due to bacterial exotoxin (edema factor), that causes endothelial damage; also hemorrhagic lymphadenitis, ascites, sepsis, bowel edema, obstruction, perforation

Gross: gastric ulceration, edema, hemorrhage

Micro: extensive acute hemorrhagic gastritis and necrosis

Gram stain: large box car shaped, encapsulated, gram positive rods of Bacillus anthracis

Reference: Archives 2003;127:761

CMV (cytomegalovirus) gastritis

Associated with bone marrow transplants, other immunosuppression

May cause perforation or fistulas

Micro: eosinophilic intranuclear inclusions, variable granular purple cytoplasmic inclusions; severe cases have ulceration, hemorrhage and perforation

Cryptosporidium

Protozoa that causes persistent watery diarrhea in AIDS patients

Micro: 2-4 micron, rounded basophilic organism adherent to surface epithelial cells

Positive stains: PAS, Giemsa, gram stain

EBV (Epstein-Barr virus) gastritis

Complication of infectious mononucleosis, usually a self-limited clinical syndrome, GI complications rare

Case report of EBV associated severe gastritis with diffuse mucosal lymphoid hyperplasia, simulating lymphoma, Archives 2003;127:478

Helicobacter heilmannii gastritis

Associated with lymphoid hyperplasia, lymphoma and peptic ulcer disease

Helical, 3.5-7.5 microns, 0.9 microns in diameter

Prefers gastric antrum; less severe and fewer lymphoid aggregates than H. pylori gastritis

Very rare compared to H. pylori; patients also are symptomatic

Symptoms: Usually dyspepsia, epigastric pain, acid reflux

Cause: contact with farm animals or household pets

Micro: long spirals; changes similar to but less severe than H. pylori gastritis (lymphoid aggregates, scant neutrophils)

Positive stains: H. pylori (cross reacts)

References: Mod Path 1999;12:534, Archives 1995;119:1149

Helicobacter pylori gastritis

Present in 90% with chronic gastritis affecting the antrum

Colonizes 50% of asymptomatic American adults by age 50; 80% of Puerto Rican adults

Most people with H. pylori infection in North America have gastritis but no symptoms; in underdeveloped countries, infected individuals usually have atrophic gastritis

Associated with 2x relative risk for gastric carcinoma

H. pylori characteristics: non-spore forming, curvilinear gram negative rod, 3.5 x 0.5 microns

Has adapted to niche provided by gastric mucus by motility (flagella) to swim through viscous mucous, urease to buffer gastric acid, adhesin to bind to gastric epithelial cells (better binding with cells that express type O antigen)

H. pylori sits on surface or in lumen, needs acid to survive, otherwise urease causes pH to be too high

More inflammation in H. pylori gastritis than NSAID gastritis

Post-treatment, chronic inflammation persists, but neutrophils, reactive epithelial changes, erosions, ulcers dissipate quickly; takes months/years for elimination of low grade MALT, lymphoid follicles, atrophy, metaplasia

Can test for mutations associated with antibiotic resistance, Archives 2001;125:493

In children in Columbia, with higher risk for gastric cancer, have more several gastric injury and less regenerative capacity - more infiltration of neutrophils and lymphocytes, more mucus depletion, higher H. pylori density; more CD8+ T cells and macrophages, fewer B cells, Hum Path 2003;34:206

Gross: red mucosa, coarser texture than normal, may have thickened rugal folds or thin/flat mucosa; with long term disease, mucosa may be thin/flat; usually affects antrum (particularly in children, Hum Path 2002;33:1133) and cardia

Micro: bacteria is curved, spirochete-like, in superficial mucus layer and along microvilli of epithelial cells; are NOT invasive; are usually not seen in areas of intestinal metaplasia; associated with chronic inflammatory infiltrate with germinal centers (follicular gastritis) and plasma cells in lamina propria; active inflammation if neutrophils in glandular or surface epithelial layer

Regenerative change: enlarged, hyperchromatic nuclei in surface epithelial cells, with diminished mucus vacuoles and frequent mitotic figures

Positive stains (for H pylori): Giemsa, Warthin-Starry, Thiazine, Diff-Quik

References: Archives 1994;118:740

Herpes simplex virus

Rare in stomach

Micro: basophilic, ground glass intranuclear inclusions in epithelial cells

Measles gastritis

Case reports, AJSP 2001;25:259, Archives 1993;117:820

Associated with upper GI bleeding

Endoscopy: erosive gastritis or ulcers with heaped, nodular edges

Micro: severe gastritis, dense plasmacytic infiltration, variable neutrophils and lymphocytes, large, bizarre inclusion bodies and clusters of multinucleated giant cells in surface epithelium and lamina propria, vasculitis without proliferative stages

Mycobacterium avium-intracellulare

Micro: lamina propria filled with monotonous infiltrate of foamy histiocytes, no granulomas

Positive stains: Ziehl-Neelson, modified Fite stain, other acid fast bacilli stains

Syphilitic gastritis

Rare

Gross: erosions or ulcers in pyloric region, progressing to shrunken fibrotic stomach resembling linitis plastica

Micro: ulcers, abundant plasma cells, fibrosis; variable endarteritis obliterans, poorly formed granulomas (gummas)

Positive stains: Steiner silver stain identifies spirochetes

Toxoplasmosis

Common opportunistic pathogen in patients with AIDS; rarely presents in stomach

Case report at Archives 2003;127:732

Toxoplasma gondii: obligate intracellular coccidian protozoan that infects humans, other mammals, birds; sexual reproduction occurs in cats; oocytes are passed in cat feces, ingested from contaminated soil, excyst in duodenum, release sporozoites that invade intestine

Infection also by ingesting viable tissue cysts in undercooked meat

Micro: variable acute and chronic inflammatory infiltrates, usually in antrum or fundus; trophozoites present

Tuberculosis

Present in stomach in 0.6% of those with obvious pulmonary tuberculosis

Predisposing factors: malnourishment, alcoholism, immunosuppression

Micro: caseating granulomas

Ulcers

Peptic ulcer disease

Ulcer: breach in muscularis mucosa of GI tract

Peptic ulcer: chronic, usually solitary, due to acid-peptic juices

Sites: duodenum, antrum, GE junction, margins of gastrojejunostomy, adjacent to Meckel diverticulum containing ectopic gastric mucosa, lower esophagus

Incidence in US: 4 million, 350,000 new cases/year; 3,000 deaths; affects 10% of American men, 4% of women (M/F = 3:1 for duodenal ulcers, 1.5-2:1 for gastric ulcers)

Incidence has decreased recently for duodenal ulcers, not for gastric ulcers

Causes: mucosal injury due to Helicobacter pylori infection, NSAID use, alcohol, smoking, corticosteroids use, Zollinger-Ellison syndrome (multiple peptic ulcerations in stomach, duodenum and jejunum due to excess gastrin secretion by a tumor), ischemia, bile/pancreatic juice reflux

Hyperacidity present in a minority of duodenal ulcers and only rarely in gastric ulcers

H. pylori physiology: produces urease (to protect it from acid), protease (breaks down glycoproteins in gastric mucus), phospholipase (damages epithelial cells, may release leukotrienes); attracts neutrophils that produce myeloperoxidase (turns HCl into hypochlorous acid, combines with NH3 to form monochloramine); both hypochlorous acid and monochloramine destroy mammalian cells

NSAID ulcers: usually moderate/severe foveolar hyperplasia, edema, vascular ectasia (indicative of reactive/chemical gastropathy), all more prominent than in non-NSAID ulcers, Mod Path 1999;12:592

Treatment: antibiotics promote healing of ulcers and reduce recurrences

Gross: usually < 4 cm, clean base (due to peptic enzymes), surrounded by erythematous mucosa

Micro: gastritis; H. pylori; ulcer may be transmural or limited to mucosa and submucosa

Acute gastric ulcer

Common autopsy finding

Causes: NSAIDs, steroid use, severe physiologic stress (shock, extensive burns, sepsis, severe trauma, increased intracranial pressure, post-intracranial surgery, intensive care unit), systemic amyloidosis, post-chemotherapy, post-radiation therapy

Curling ulcer: stress ulcer in proximal duodenum associated with severe burns or trauma

Cushing ulcers: ulcers in esophagus to duodenum associated with intracranial injury or surgery; have high incidence of perforation

Stress ulcers heal in days-weeks

Complications: bleeding, perforation, obstruction from edema/scarring

Treatment: correct underlying disorder

Note: mucosal lesions can heal completely, ulcers that penetrate muscularis propria undergo fibrosis, leaving a depression

Micro: usually < 1 cm, circular, small; brown ulcer base (digested blood), anywhere in stomach, often multiple, no induration of margins of ulcer; abrupt lesions with normal adjacent mucosa; no scarring or blood vessel thickening

Chronic peptic ulcer

Usually in pyloric-type mucosa along lesser curvature

20% have coexisting duodenal ulcer; 5% are multiple

Mean age 50 years, but may occur in children

Multiple (~10) biopsies recommended to rule out malignancy

Symptoms: epigastric burning; pain worse at night, within 1-3 hours after meals; pain may decrease with food/alkali; perforation associated with pain in back, left upper quadrant, chest

Usually impairs life but doesn’t shorten it; heals in 15 years without treatment versus weeks with treatment

Treatment: H2 blockers, proton pump inhibitors

Complications: perforation, hemorrhage, obstruction, surgery

Gross: usually sharply punched out defect with straight walls, NO heaped up margins; size doesn’t predict malignancy

Micro: muscle wall replaced by fibrous tissue; serosal fibrosis; hyperplasia of adjacent lymph nodes; proximal mucosa may be overhanging; distal mucosa may have ladder-like configuration; accompanied by active and chronic inflammation, unless NSAID related

Active ulcers have 4 zones: (a) surface neutrophils, bacteria, necrotic debris and possibly Candida; (b) fibrinoid necrosis at base and margins, (c) granulation tissue with chronic inflammatory cells, (d) fibrous or collagenous scars in muscularis propria with thickened blood vessels showing endarteritis obliterans

Healing ulcers: have regenerating epithelium over the surface; may have intestinal metaplasia, marked reactive changes

Rarely exhibits hyalinization (severe thickening, usually of submucosa), Archives 1982;106:472

DD: acute gastric ulcers due to severe systemic stress, carcinoma (radiologically)

Other non-neoplastic lesions

Amyloid

Deposition of insoluble extracellular protein, usually AL (light chains associated with myeloma) or AA (acute phase proteins secondary to chronic inflammation or familial Mediterranean fever) types; also associated with chronic dialysis; rarely idiopathic

70% of cases of AL amyloidosis and 55% of AA amyloidosis involve GI tract, often stomach

Primary amyloidosis (AL) patients often have monoclonal proteins in serum/urine

Symptoms: frequently none; bloating, pain, obstruction, hematemesis, hemorrhage

Gross: usually normal (multiple biopsies recommended in patients with systemic amyloidosis)

Micro: usually diffuse, may form a mass; often infiltration around blood vessels deep to mucosa; appears as amorphous, waxy, salmon pink material, often with chatter artifact

Positive stains: Congo red (red/green birefringence under polarized light), Thioflavin immunofluorescence

EM: 7.5 to 10 nanometer fibrils in twisted beta-pleated sheets

Aneurysms

Aka caliber-persistent artery, Dieulafoy’s disease

Stomach

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Normal anatomy

Mucosal protection against autodigestion

Non-neoplastic anomalies

Gastric gland heterotopia