Stomach
11 January 2006, links checked 24 February 2006
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Stomach - table of contents
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
Primary references
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 anatomy
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
Gross images: image1, image2, antrum
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
Micro images: histology of entire stomach
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
Micro images: area adjacent to squamocolumnar junction, cardiac mucosa#1, #2
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)
Micro images: fundic mucosa#1, #2, #3
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
Micro images: antral/pyloric mucosa#1, #2, #3
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
Micro images: image1
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
Micro images: gastrin immunostain
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
Ganglion cells: micro image
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
(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
Non-neoplastic anomalies
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
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
Micro images: image1, image2, image3
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
Gross images: image1
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
Micro images: image1
Micro images (Mod Path subscribers): image1, image2
Immunofluorescence images: antibodies in pernicious anemia
References: Mod Path 2002;15:102, Mod Path 2003;16:325
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
Micro images (Mod Path subscribers): image1
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%
Micro images (Mod Path subscribers): image1, image2
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
Micro images: antrum, fundus, intestinal metaplasia, inflammatory infiltrate, enterochromaffin cell hyperplasia
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
References: AJSP 2000;24:167, AJSP 2000;24:402
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)
Micro images: chronic atrophic gastritis with intestinal metaplasia
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
Micro images: image1, image2, figures 2-4, celiac disease
References: AJSP 2001;25:1174, Mod Path 2000;13:591
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