
22 July 2003, copyright (c) 2003, PathologyOutlines.com, LLC
Primary references, normal anatomy, normal histology
Congenital anomalies: achalasia of cardia, arteriovenous malformation, diaphragmatic hernia, gastric dilation, gastric gland heterotopia, heterotopic pancreas/pancreatic metaplasia, mucolipidosis, pyloric stenosis
Gastritis: features to report, active, allergic, autoimmune, carditis, Crohn’s disease, chronic, chronic atrophic, collagenous, eosinophilic, erosive, granulomatous, graft versus host disease, hemorrhagic, ischemic, lymphocytic, malakoplakia, pseudomembranous, reactive (chemical) gastropathy, suppurative, ulcerative colitis
Infections: anthrax, Candida, CMV, Cryptosporidium, EBV, Helicobacter heilmannii, Helicobacter pylori, herpes simplex, measles, mycobacterium avium-intracellulare, syphilis, toxoplasmosis, tuberculosis
Ulcers: peptic ulcer disease, acute gastric ulcer, chronic peptic ulcer
Other non-neoplastic lesions: amyloid, aneurysms, antral vascular ectasia, bezoars, calcinosis, chloral hydrate, colchicine toxicity, cyanide, cysts, diverticula, duplication, iron, kayexelate, proton pump inhibitors, xanthoma
Polyps: adenoma, Cowden’s, Cronkhite-Canada, familial colonic polyposis, foveolar hyperplasia, fundic gland, gastritis cystica polyposa, hyperplastic, inflammatory fibroid, juvenile, mixed, Peutz-Jeghers
Hypertrophic gastropathy: enlarged mucosal folds, hypertrophic hypersecretory gastropathy, Menetrier’s disease, Zollinger-Ellison syndrome
Dysplastic like changes: dysplasia, histologic treatment effect/chemoradiation therapy
Carcinoma: general, intestinal, diffuse, intramucosal, GE junction, adenocarcinoma with rhabdoid features, adenosquamous, amphicrine, carcinoid, hepatoid, lymphoepithelioma-like, neuroendocrine, oncocytic, Paneth cell, sarcomatoid, small cell, squamous cell
Lymphoma: general, lymphoid hyperplasia, anaplastic large cell, diffuse large B cell, Hodgkin’s, MALT, mantle cell, T cell
Stromal/other tumors: adenosarcoma, alveolar soft parts sarcoma, choriocarcinoma, elastofibroma, follicular dendritic cell sarcoma, GANT, GIST, glomus, granular cell, Langerhans’ cell histiocytosis, leiomyoma, lipoma, malignant fibrous histiocytoma, metastases to stomach, schwannoma, synovial sarcoma, teratoma
Miscellaneous: staging, grossing specimens, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), March 1977 to May 2003
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to June 2003
Human Pathology (Hum Path), September 1998 to May 2003
Modern Pathology (Mod Path), January 1999 to May 2003
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Please refer to these primary references for more detailed discussions and photographs
Normal volume is 1.5 liters, capacity is 3 liters
Rugae are coarser proximally and when stomach is empty
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
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)
(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
(c) intercellular tight junctions prevent back-diffusion of H+; disruptions are quickly repaired
(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
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
Rare, case report of incidental finding with amyloid deposits at autopsy in 74 year old man, Archives 1986;110:69
Defective closure of diaphragm, usually left sided
Hernia sac usually contains all/part of stomach
May cause newborn respiratory insufficiency
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
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 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
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
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
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
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
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
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
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 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 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)
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
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
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)
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
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
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
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
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
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
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
Rare; variable changes include multiple tiny shallow ulcers, crypt abscess formation, increased intraepithelial lymphocytes, villous blunting
Microscopic findings parallel remissions and relapses of colonic inflammation
Infections
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
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
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
Rare in stomach
Micro: basophilic, ground glass intranuclear inclusions in epithelial cells
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
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
Present in stomach in 0.6% of those with obvious pulmonary tuberculosis
Predisposing factors: malnourishment, alcoholism, immunosuppression
Micro: caseating granulomas
Ulcers
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
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
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
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
Aka caliber-persistent artery, Dieulafoy’s disease