Stomach
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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
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
(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
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
Usually single, submucosal, high on lesser curvature
Complications: perforation, hemorrhage
Micro: large tortuous vessel with small defect in overlying mucosa; may have amyloid
References: AJSP 1982;6:83
Aka watermelon stomach, gastric antral vascular ectasia (GAVE)
Acquired vascular disease that may cause blood loss and iron deficiency anemia due to chronic antral hemorrhage
Associated with connective tissue diseases, particularly systemic sclerosis
Endoscopy: parallel red stripes (hyperemic streaks) at antral mucosal folds resemble watermelon stripes
Micro: minimal changes; increase in blood vessel number and diameter with fibrin thrombi, fibromuscular hyperplasia; reactive foveolar epithelial changes
DD: portal hypertension (causes vascular ectasia with different endoscopic appearance, no acute erosions, no fibrin thrombi), Dieulafoy’s lesion (caliber persistent artery of stomach - large diameter artery in gastric submucosa that compresses mucosa, causing erosion, bleeding from artery; 60% mortality)
References: Archives 2002;126:375, AJSP 1987;11:750
Foreign bodies composed of hair or vegetable matter
Phytobezoars: plant material concretions; usually caused by ingestion of unripened persimmons; stomach acid causes polymerization of tannin monomers in fruit, causing a tannin-cellulose-hemicellulose-protein complex; dissolves with cellulase, Archives 1980;104:159
Trichobezoars: aka hairballs; ingested hair coated with decaying food; associated with partial gastrectomy, partial outlet obstruction, lack of teeth, vagotomy
Associated with organ transplant patients or ulcer patients taking aluminum-containing antacids or sucralfate
Micro: calcium deposits resemble CMV inclusions, 40-250 microns, just beneath surface epithelium at foveolar tips
References: AJSP 1993;17:45
Intensely pink gastric mucosa, Int J Legal Med 1999;112:317
Colchicine is used to treat gout, toxicity can cause chronic renal failure and death
Features are associated with toxicity only, not therapeutic colchicine without toxicity
Micro: mitoses arrested in metaphase (ring formation), epithelial pseudostratification, loss of polarity, abundant crypt apoptotic bodies in gastric antrum but not in gastric body
References: AJSP 2001;25:1067
Gastric mucosa is markedly pink/red, Archives 2002;126:400
Intramucosal cysts most common; associated with intestinal metaplasia; various linings
Submucosal cysts aka gastritis cystica profunda
Cysts may also be part of Menetrier’s disease
Intramucosal cysts in body in 70% with Zollinger-Ellison syndrome, may give rise to fundic gland polyps, severity associated with serum gastrin, Hum Path 2000;31:140
Probably due to anatomically weak areas
May be associated with peptic ulcer
Rare, usually girls
Cyst (unilocular, multilocular) lined by gastric mucosa within abdomen; usually does not communicate with normal stomach
Fills with fluid, presents as palpable mass
Pyloric duplication usually is acquired and due to extensive peptic ulceration
Iron overdose may cause severe gastrointestinal necrosis and stricture
Therapeutic iron causes brown crystalline iron material in superficial gastric biopsies, often mixed with fibrinoinflammatory exudate; usually (83%) associated with erosive or ulcerative mucosal injury, although this may also be due to other disorders, AJSP 1999;23:1241
Kayexelate (sodium polystyrene sulfonate) in sorbitol, used to treat hyperkalemia, may crystallize in the stomach and produce endoscopic findings resembling gastric bezoar, ulcer or erosion
Micro: crystals are lightly basophilic with a faint crystalline mosaic pattern, better seen with PAS/Alcian blue; crystals are refractile but not polarizable, luminal and adherent to intact surface epithelium or mixed with inflammatory exudates in patients with ulcer or erosion
Reference: AJSP 2001;25:637
Includes omeprazole
Used to treat gastroesophageal reflux disease (GERD)
Patients may develop G-cell and enterochromaffin cell-like hyperplasia, secondary to drug-induced achlorhydria
Long-term therapy associated with fundic gland polyps (sessile, multiple, <1.0 cm); present in 17% after 3 months, in 35% after 5 months treatment; polyps regress when treatment stops, Hum Path 2000;31:684
Micro: glandular luminal dilatation with swelling and bulging of the superficial cytoplasm of parietal cells (so-called parietal cell protrusion); glands lined by cells with serrated rather than a smooth border
Aka xanthelasma, lipid islands
No clinical significance; common in Japan
May be due to bile reflux
Case report of xanthoma and hyperplastic gastric polyposis, Archives 1989;113:428
Gross: small yellow / cream colored intramucosal lesion, < 5 mm, single or multiple
Micro: foamy histiocytes with neutral fat in the lamina propria
Negative stains: PAS
DD: signet ring carcinoma
Polyps
Represents 5% of polypoid lesions in stomach; relatively rare in Western populations
Precursor lesion of gastric adenocarcinoma; 40% contain focus of carcinoma at time of diagnosis; 30% risk of carcinoma in adjacent mucosa; 3% progress to carcinoma in 7 years (higher risk of carcinoma than colonic adenomas)
Associated with autoimmune gastritis, intestinal metaplasia, familial adenomatous polyposis
Considered to be analogous to colonic dysplasia-associated masses arising in setting of chronic inflammatory bowel disease, as they arise in a background of atrophic gastritis (metaplastic or autoimmune)
Only rarely associated with reactive/chemical gastropathy or post-antrectomy
Case reports of Paneth cell adenoma, AJSP 1989;13:325, Archives 1989;113:129
Treatment: complete excision, biopsy of nonpolypoid antrum and body
Gross: single, in antrum, up to 3 cm, sessile or pedunculated; rarely are depressed mucosal lesions
Micro: polypoid projections of dysplastic epithelium (by definition) with pseudostratification, nuclear abnormalities, mitotic figures overlying cystically dilated glands without dysplastic changes; villous or tubular or both; contains scattered endocrine cells, Paneth cells; associated with atrophy and intestinal metaplasia
High grade: cribriforming and marked cytologic atypia
Intestinal type: focal goblet cells or Paneth cells; more likely to show high grade dysplasia or adenocarcinoma within the polyp or a separate adenocarcinoma; associated with intestinal metaplasia and H. pylori gastritis
Gastric type: lined entirely by gastric mucin cells on PAS/Alcian blue stain; distributed throughout stomach, 82% solitary, not associated with coexisting carcinoma, background mucosa usually normal
Indeterminate: cannot determine due to lack of mucin production
Positive stains: CEA, p53
References: AJSP 2002;26:1276
Aka multiple hamartoma syndrome
Rare; tricholemmomas on face, GI polyps, increased incidence of breast and thyroid carcinomas
Gross: small (1-2 mm), sessile polyps
Micro: excess lamina propria splayed and dissected into lobules by disorganized fascicles of muscularis mucosa running upward from base of mucosa
Very rare juvenile polyposis disorder with diffuse GI polyposis, alopecia, hyperpigmentation, dystrophic changes in fingernails and toenails
Occasionally gastric adenocarcinoma
Micro: broad sessile base, expanded edematous lamina propria, cystic glands
DD: juvenile polyps (similar, but no other features of this syndrome)
References: AJSP 1989;13:940, AJSP 1985;9:65, Archives 1977;101:432
Related to Gardner’s syndrome
50% have gastric involvement with adenomatous, hyperplastic or fundic gland polyps
May have adenocarcinoma or carcinoid tumor of stomach
May represent early hyperplastic polyp
Associated with chronic atrophic gastritis
Fundic gland polyp
Single or multiple small (2 mm) polypoid projections in gastric fundus / body
Considered to be hamartomas or peculiar form of hyperplastic polyp
Either sporadic or associated with familial adenomatosis polyposis syndrome, tuberous sclerosis
Multiple polyps associated with protein pump inhibitors; fundic gland cysts are associated with increasing periods of treatment with omeprazole for GERD, and with H. pylori eradication, Hum Path 2000;31:684
In familial adenomatous polyposis syndrome, occur with increased frequency, 25% are dysplastic vs. 1% of sporadic fundic gland polyps, AJSP 1998;22:293
Sporadic cases associated with loss of immunoreactivity for tuberin, a protein altered in tuberous sclerosis, Mod Path 2002;15:862
Patients with 10+ polyps often have beta-catenin mutations, Mod Path 2002;15:718
Gross: minute mucosal bumps 1-5 mm, usually 1-20, may be part of diffuse fundic gland polyposis (100+ polyps)
Micro: dilated glands / microcysts lined by fundic epithelium; shorted foveola, increased smooth muscle in lamina propria, no proliferation of foveolar epithelium
Aka polypoid mucosal prolapse
Gross: usually on gastric side of gastroenterostomy stomas; large sessile polyp
Micro: resembles gastric hyperplastic polyp and reflux gastritis with pit hyperplasia, distortion, dilation; may have submucosal cysts due to downward proliferation of epithelium
Aka inflammatory, regenerative polyps
Different from colonic hyperplastic polyps; similar to inflammatory colonic pseudopolyps
Non-neoplastic, represents 75-90% of all gastric polyps
Associated with background mucosal disease in 85% of cases, particularly chronic gastritis with glandular atrophy and intestinal metaplasia; H. pylori gastritis, chemical (reactive) gastropathy; thus, endoscopists should also biopsy surrounding mucosa to evaluate underlying gastric abnormalities
Also associated with hypochlorhydria and hypergastrinemia
Multiple polyps associated with autoimmune gastritis
Patients usually age 50+
Rare/no malignant potential by itself, although present in 20% of stomachs resected for carcinoma (chronically inflamed and atrophic mucosa tends to form hyperplastic polyps and to degenerate into malignancy)
Hyperplastic polyps with even low grade dysplasia may have significant risk for associated carcinoma, Hum Path 2002;33:1016
Gross: small (mean 1.4 cm, range 0.5 to 2 cm), sessile, multiple (20%), 60% in antrum; smooth or slightly lobulated; central umbilication common
Micro: elongated, tortuous or dilated gastric foveola with pyloric or fundic glands; lamina propria has inflammatory cells, scattered smooth muscle bundles, edema, patchy necrosis; associated with chronic, active (H. pylori) and atrophic autoimmune gastritis; rarely foamy macrophages
Surface mucosa may be regenerative, but dysplasia in only 4%; focal intestinal metaplasia in 16%
References: AJSP 2001;25:500
Non-neoplastic / benign
Formerly known as eosinophilic granuloma
Associated with achlorhydria, hypochlorhydria, pyloric obstruction
Usually antral; may occlude pyloric channel
Rarely associated with adenocarcinoma or adenoma, Archives
1988;112:829
Treatment: local excision
Gross: sessile or pedunculated; largest was 9 cm
Micro: submucosal lesion with whorls of granulation tissue-like vessels, fibroblastic cells and prominent inflammatory response, primarily eosinophils; also plasma cells and mast cells; minimal mitotic activity
Positive stains: vimentin (100%), CD34, variable smooth muscle actin, HHF-35
Negative stains: CD117 (although mast cells are CD117+), S100
EM: myofibroblasts
References: AJSP 1993;17:1159
Aka retention polyp
Associated with increased risk of colorectal and gastric carcinoma
Gross: smooth-surfaced, 1-2 cm, short narrow stalk
Micro: irregular cysts in lamina propria with normal gastric epithelium; may have stromal hemorrhage, surface ulceration and chronic inflammation due to torsion
DD: hyperplastic polyp (usually background mucosal disease)
Hyperplastic and neoplastic
DD: hyperplastic polyps with reactive epithelial changes at their surface
Usually children/teenagers
20% of Peutz-Jeghers patients have hamartomatous gastric polyps
Rarely associated with gastric adenocarcinoma, Archives 1982;106:517
Gross: 1-3 cm, short broad stalk, coarsely lobulated
Micro: core of finely arborizing branches of smooth muscle from muscularis mucosa; covered by normal but often disorganized mucosa; usually no prominent inflammation; pseudoinvasion in 10% (no atypia, normal epithelial cell subtypes, brush border, hemosiderin deposition, intramural mucinous cysts, AJSP 1987;11:743)
Hypertrophic gastropathy
Often normal variant due to excessively long mucosal cores covered by normal mucosa
Other causes: H. pylori gastritis, lymphocytic gastritis, peptic ulcer disease (edematous and inflamed mucosa), rarely carcinoma or lymphoma, hypertrophic gastropathy
May be histologic-clinical discordance, AJSP 1991;15:577
Hypertrophic hypersecretory gastropathy
Very rare
Cases without protein loss are similar to ZE syndrome, but no pancreatic tumors, no G cell hyperplasia, no hypergastrinemia; parietal cells may be overly sensitive to normal serum gastrin levels
Cases with protein loss resemble Menetrier’s disease, but also have hypergastrinemia
Menetrier’s disease
Described by Menetrier in 1888 as polyadenomes en nappe
Definition: giant mucosal folds involving fundus, usually spares antrum; low acid production even after stimulation; mucosal protein loss; gastric pit hyperplasia and glandular atrophy
Peripheral edema present due to mucosal protein loss
75% men; mean age 30-50’s; occasionally children
Self-limited in children; in adults, chronic and severe - may require partial gastrectomy
Usually greater curvature of stomach
Grossly and radiologically resembles Zollinger-Ellison syndrome
Gross: markedly hypertrophic gastric folds resembling cerebral convolutions; abrupt transition to normal mucosa
Micro: marked foveolar hyperplasia, tortuous (corkscrew) and cystically dilated foveolar glands; may extend into muscularis mucosa; atrophic glandular compartment; edematous and inflamed lamina propria
DD (clinically): lymphoma and carcinoma, varioliform gastritis (hypertrophic lymphocytic gastritis)
Localized Menetrier’s disease
Rare localized hyperplastic gastropathy, associated with stomach adenocarcinoma, AJSP 1997;21:1334
Symptoms: upper abdominal discomfort, loss of appetite, weight loss, anemia, occasionally hypoproteinemia
Gross: circumscribed area of giant folds, well demarcated from surrounding normal-appearing mucosa; usually in body or antrum
Micro: increase in epithelial cell mass of mucous cells with long, sometimes cystically dilated foveola, mild inflammatory infiltrate
Grossly and radiologically resembles Menetrier’s disease
Associated with MEN1 syndrome and multicentric carcinoid tumors, AJSP 1990;14:503
Intramucosal cysts in body in 70%, may give rise to fundic gland polyps, severity associated with serum gastrin levels, Hum Path 2000;31:140
Symptoms: duodenal ulceration, diarrhea
Physiology: gastric gland hyperplasia caused by serum hypergastrinemia from pancreatic or duodenal neoplasm, or rarely by primary G cell hyperplasia of antral mucosa
Gross: enlarged fundic mucosal folds with cerebriform pattern
Micro: hyperplasia primarily of parietal cells in fundic glands; normal antral glands and gastric pits
Dysplasia-like lesions
Indicates possible coexisting carcinoma or high risk for developing carcinoma (particularly for high grade lesions, AJSP 1987;11:788)
Term used for flat lesions, although adenomas also have dysplastic features
Indefinite for dysplasia: low grade features in a background of marked active inflammation or erosion with milder nuclear hyperchromatism and stratification
Low grade dysplasia: nuclear enlargement, hyperchromatism, stratification
High grade dysplasia: severe cytologic atypia, glandular cribriforming or full thickness nuclear stratification
Frequently classified as carcinoma in Japan, AJSP 1999;23:511
Papova classification (AJSP 2000;24:167)
1 = normal: normal, reactive foveolar hyperplasia, intestinal metaplasia (complete or incomplete)
2 = indefinite for dysplasia: foveolar hyperproliferation or hyperproliferative intestinal metaplasia
3 = noninvasive neoplasia: low grade, high grade (includes suspicious for in situ [intraglandular] and in situ)
4 = suspicious for invasive cancer
5 = cancer
Micro: increased cell proliferation, abnormal cell size, configuration and orientation; reduced / absent mucus secretion, increased N/C ratio, loss of nuclear polarity, pseudostratification, cellular crowding;
mild, moderate or severe (carcinoma in situ)
Positive stains: p53, MIB1 in deep and superficial epithelium
DD: reactive epithelial changes after mucosal injury (uniform cells, basal or central nuclei, minimal pseudostratification; more atypical changes are associated with inflammatory infiltrate), radiation/chemotherapy atypia
Aka post-chemotherapy / radiation therapy changes
Occurs in 8% of patients with chemoradiation therapy for esophageal carcinoma, may be confused with dysplasia
Also occurs after hepatic artery infusion chemotherapy, AJSP 1983;7:261
After preoperative chemotherapy, may see reduction in tumor cellularity, increase in dense fibrosis, formation of large mucin pools with lymphocytes and macrophages; in signet-ring carcinomas, see smaller intracytoplasmic mucin vacuoles; often see no effect, Archives 1991;115:807
Gross: flat appearance
Micro: patchy distribution, foveolar and gland involvement, surface maturation, open nuclear chromatin pattern with prominent nucleoli, retention of nuclear polarity, mitoses confined to pits, lack of atypical mitoses, cytoplasmic eosinophilia or vacuolization, no intestinal metaplasia, no irregular glandular microcystic change, no increased nuclear/cytoplasmic ratio; p53-, MIB1+ only in deep foveolar epithelium
Also, bizarre nuclear atypia, endarteritis obliterans
References: Mod Path 2001;14:389
Carcinoma
22K cases/year in US; overall rates declining due to lower rates of intestinal type; diffuse rates unchanged
90% of all malignant tumors in stomach are carcinomas
High incidence in Japan, Chile, Italy, China, Portugal, Russia; kills more people worldwide than lung cancer
2/3 men; associated with lower socioeconomic groups
In young patients, associated with radiation therapy or chemotherapy for other malignancies
5 year survival - 20% or less; 95% for surgically treated early gastric carcinoma
Nodal involvement may not alter survival
Usually asymptomatic until late; weight loss, abdominal pain, nausea, vomiting, altered bowel habits
Japan: mass endoscopy programs led to 35% early gastric cancers vs. 10% in US
Well differentiated tumors may grow very slowly, Archives 1990;114:1046
Rarely occurs in gastric stump after partial gastrectomy for ulcer, Archives 1985;109:958
Minute (< 5 mm) poorly differentiated tumors may show no gross features, Archives 1989;113:926
Phenotypes: intestinal (arises from complete-type intestinal metaplasia) and gastric (arises directly from gastric foveolar epithelium, poorer prognosis)
Pattern of allelic loss resembles colon carcinoma (c-met, K-ras, HER2 [5-15%], p53 [50%])
Microsatellite instability phenotype cancers (10% prevalence) are associated with fewer lymph node metastases, borderline significant improved survival, Mod Path 2002;15:632; minimal dysplasia, Mod Path 1999;12:15; patients with gastric and colorectal cancers often (18%) have this phenotype, Mod Path 2001;14:543
Site: pylorus and antrum > cardia; lesser > greater curvature
Depth of invasion most important prognostic factor
Metastases to supraclavicular nodes (Virchow’s node, Trousseau’s sign) may be first clinical manifestation
Death due to widespread seeding of peritoneum and lung/liver metastases; also distant metastases to adrenal gland, peritoneum, ovary, spleen (#2 cause of splenic metastases, Archives 2000;124:526)
Locally invades esophagus (proximal carcinomas), duodenum (distal carcinomas), omentum, colon, pancreas, spleen
Kruckenberg tumor: metastases to one or both ovaries; rarely has tubular pattern, AJSP 1981;5:225
Early: confined to submucosa, regardless of perigastric nodal metastases
Advanced: muscularis propria invasion
Exophytic: protrudes into lumen
Flat/depressed: no obvious tumor in mucosa
Excavated: erosive crater in stomach wall; resemble peptic ulcers, but advanced cancers have heaped up, beaded margins and shaggy, necrotic bases
Treatment: gastrectomy
Poor prognostic factors: younger age (usually diffuse histology, more advanced disease), proximal half of stomach, deep invasion, infiltrative margin, diffuse histologic type, positive surgical margins (predicts local recurrence), lymph node metastases, reduced neutrophilic infiltration (women in high risk area in Italy, Mod Path 2002;15:831)
Mucosal lymphangiectasia common, and associated with nodal metastases, Archives 1996;120:78
Positive stains: CDX2 (AJSP 2003;27:303), CK7 (71%, Hum Path 2002;33:1078), CK20 (41%)
Negative stains: CD44 (Archives 2000;124:212), EBV (except for lymphoepithelioma-like carcinomas and rarely classic carcinomas, Mod Path 1999;12:873)
Intestinal type adenocarcinoma
Bulky tumors composed of glandular structures
Mean age 55, 2/3 men
Incidence has declined in last 50 years
Risk factors: diet (nitrates, smoked and salted foods, pickled vegetables, lack of fresh fruit and vegetables [green leafy vegetables, citrus fruit]), low socioeconomic status, cigarette smoking [RR: 1.5-3.0 x]
Host factors: chronic gastritis (achlorhydria favors Helicobacter pylori growth, intestinal metaplasia is a precursor lesion), H pylori infection, autoimmune gastritis, partial gastrectomy (favors reflux), gastric adenomas, Barrett’s esophagus
Genetic: slightly increased risk with blood group A, family history, hereditary nonpolyposis colon cancer syndrome
Not risk factors: alcohol, antacids, occupational exposure
Micro: neoplastic intestinal glands resembling colonic adenocarcinoma; contain apical mucin vacuoles; variable calcification, endocrine cells, rare Paneth cells
Well differentiated: columnar cells that secrete mucin, rarely are ciliated
Poorly differentiated: solid pattern
Positive stains: acid mucins (Alcian Blue, colloidal iron), p53 (usually)
Well differentiated adenocarcinoma mimicking complete intestinal metaplasia
Neoplastic tubules have branching, tortuous, anastomosing and plexiform structures
May need several biopsies for correct diagnosis, Hum Path 1999;30:826
Diffuse type adenocarcinoma
Infiltrative growth of poorly differentiated discohesive malignant cells
Aka linitis plastica or signet ring adenocarcinoma
Mean age 48, M=F; more common in gastric cancers in the young
No reduction in incidence over past 50 years
Appears to arise without dysplastic precursor, possibly through primary involvement of genes affecting cell-cell and cell-matrix junctional proteins, AJSP 1996;20 Supp 1:S8
No known risk factors
Linitis plastica: broad region of gastric wall or entire stomach is extensively infiltrated by malignancy, creating a thickened, rigid, leather bottle-like stomach; may cause pyloric obstruction
Micro: gastric-type mucus cells, usually do NOT form glands, infiltrate as individual cells or small clusters, may be transmural; appear to arise from middle layer of mucosa; intestinal metaplasia usually not present; numerous signet ring cells seen (mucin pushes nucleus to periphery); submucosal fibrosis present, variable mucosal ulceration; hypertrophic muscularis propria; may have marked desmoplastic and inflammatory reaction
Positive stains: mucicarmine, Alcian blue-PAS, CEA, EMA, keratin, villin
Negative stains: TTF-1, p53 (usually)
DD: metastases from breast (Archives 2001;125:567), lung; reactive epithelial atypia associated with chemotherapy or otherwise; xanthoma; lymphoma with artifactual signet ring cells due to cytoplasmic shrinkage (Archives 1997;121:623)
Limited to mucosa, regardless of nodal metastases
5% have nodal metastases
More common in Japan (34%) due to aggressive screening
5 year survival is 80-95%, even with nodal metastases
GE junctional adenocarcinomas
Heterogeneous group of tumors: from distal esophagus associated with Barrett’s esophagus, cardia adenocarcinomas, subcardial gastric carcinomas which secondarily invade GE junction
Distal esophagus: usually men, associated with Barrett’s esophagus (intestinal metaplasia) and reflux, less likely to have diffuse growth pattern, lower incidence of lymphatic spread, CK7+
Cardia: usually men, usually not associated with Barrett’s esophagus, higher frequency of diffuse pattern, although most are still intestinal
Positive stains: CK7/19 (44%), CK20 (55%)
References: AJSP 2002;26:1213
DD: adenocarcinoma of distal esophagus (74% are CK7+/CK20- vs. 24% of GE junctional adenocarcinomas)
Adenocarcinoma with rhabdoid features
Rare
Very aggressive (usually death within 1-6 months after surgery)
Micro: solid, diffuse or alveolar growth of tumor cells with poor or no cohesiveness, large cells with eosinophilic cytoplasmic inclusions that indent nucleus
Positive stains: keratin, vimentin
References: AJSP 1993;17:813
Behavior determined by glandular component
Positive stains: CD44 (squamous component, Archives 2000;124:212)
Mixed neuroendocrine and non-neuroendocrine carcinomas
Case reports at Archives 2001;125:1513, AJSP 1991;15:592
Slow growing
Associated with achlorhydria, antral G cell hyperplasia, hypergastrinemia, diffuse enterochromaffin-like cell hyperplasia, AJSP 1987;11:909, AJSP 1987;11:435
Enterochromaffin-like (ECL) cells: non-peptide secreting endocrine cell of gastric fundus/body mucosa; comprises 30% of endocrine cells; releases histamine in response to gastrin production by G cells; long term gastrin stimulation causes ECL hyperplasia
Type 1: in patients with autoimmune chronic atrophic gastritis; occur in 5-10%, usually women, mean age 63 years; arise due to enterochromaffin-like cell hyperplasia and hypergastrinemia secondary to parietal cell loss, in fundus/body; 57% multifocal; 97% less than 1.5 cm; 91% limited to mucosa or submucosa; only 2-5% associated with liver metastases; almost never causes death
Type 2: in patients with Zollinger-Ellison syndrome, usually also MEN-1; no gender predilection, mean age 50 years; associated with ECL cell hyperplasia and hypergastrinemia; usually multicentric in body/fundus; 23% > 1.5 cm, 30% with local nodal metastases, 10% with liver metastases; death more likely from gastrinomas of Zollinger-Ellison syndrome than from the carcinoid tumors
Type 3: not related to hypergastrinemia or ECL cell hyperplasia; usually solitary, may not be in body/fundus; 74% in men, mean age 55 years; 76% deeply invasive, 71% have nodal metastases, distant metastases common
Type 4: very rare (<10 cases), due to defective gastric acid secretion
Metastases only to regional lymph nodes and liver, but patients may still have long term survival
Case reports of carcinoid tumors with adenocarcinoma, Archives 1991;115:1006, Archives 1988;112:91
Treatment: antrectomy (removes gastrin stimulation, Archives 1994;118:658), excision of tumors
Gross: small, sharply outlined, covered by flattened mucosa; resemble polyps
Micro: glandular, trabecular or rarely insular patterns; bland nuclei with salt and pepper chromatin, rare mitotic figures, prominent vessels, no necrosis
Positive stains: chromogranin, keratin, neuron-specific enolase
Negative stains: CK7, CK20 (Hum Path 2001;32:1087)
EM: dense core secretory granules
Clear cell variant
Case report of tumor composed entirely of clear cells with foamy cytoplasm at Archives 1997;121:1100.
Gross: yellow, resembles gastric xanthoma
Micro: uniform clusters of polygonal cells with foamy cytoplasm; abundant vascular stroma
Positive stains: chromogranin A
EM: dense core neurosecretory granules
Enterochromaffin-like (ECL) cell tumors
Multiple, polypoid, throughout fundus
May be hyperplastic and not a neoplastic lesion
Micro: smooth muscle proliferation, associated with atrophic gastritis with intestinal metaplasia
Negative stains: H. pylori
References: AJSP 1995;19 Suppl 1:S20
Gastrinoma
Solitary, usually in antrum
Positive stains: gastrin
Poor prognosis
Gross: nodular or massive growth, extensive venous invasion
Micro: glandular and hepatocellular differentiation; abundant cytoplasmic glycogen, hyaline globules; may have tubulopapillary pattern with clear cells; may secrete bile
Positive stains: polyclonal CEA (canalicular pattern), AFP (50%, positive in classic gastric adenocarcinomas also)
Lymphoepithelioma-like carcinoma
Resembles similar tumor elsewhere
Micro: poorly differentiated carcinoma with lymphoid stroma
Positive stains: EBV
References: Archives 1994;118:998
May have a poor outcome in MEN1 patients, AJSP 1997;21:1075
Mean age 70 years (range 44-92 years), 70% men
Poorly prognosis than non-neuroendocrine carcinomas; similar prognosis for small cell and large cell neuroendocrine carcinomas, Archives 1998;122:1010
Most gastric carcinomas contain scattered cells (small percentage of tumor) with neuroendocrine differentiation, Archives 1996;120:478; don’t call them neuroendocrine carcinomas
Gross: ulcerated or fungated
Micro: solid, organoid, trabecular, pseudoglandular, spindle cell or rosette-like patterns; small cell or large cell patterns
Aka parietal cell/gland carcinoma
Rare, <50 cases reported
Elderly patients, ages 58-81 years
Resemble parietal cells, but antiparietal cell antibodies were nonreactive in AJSP 2002 study
Cases from other studies may have parietal cell origin, but need antiparietal cell antibody testing
Micro: moderate to well differentiated adenocarcinomas or sheets of cells with abundant eosinophilic, finely granular cytoplasm resembling parietal cells
Positive stains: PTAH, Luxol fast blue
Negative stains (rare cells positive): PAS, Alcian blue, MUC2
EM: abundant mitochondria, tubulovesicles, intracellular canaliculi, intercellular lumina with long microvilli
References: AJSP 2002;26:458
Paneth cell carcinoma
Case report at Archives 1989;113:129
Aka carcinosarcoma
Glandular and malignant spindle cell components
Aggressive clinical course
By definition, must be surrounded on all sides by gastric mucosa; otherwise may be esophageal carcinoma with gastric extension
Usually have small glandular component if searched for
Case report of tumor in gastric stump, AJSP 1989;13:317
Lymphoma
Similar to intestinal lymphomas, usually B cell
Most cases represent disseminated disease; but stomach is common site for extranodal, non-Hodgkin’s lymphoma
Most patients age 60+
Clinically resembles carcinoma, but usually a better prognosis
Associated with erosion (61%), intestinal metaplasia (59%), H. pylori (57%), atrophy (37%), dysplasia (4%), Archives 2000; 124:1628
Micro: highly suggestive features for low grade lymphoma versus inflammation are dense lymphoid infiltrates with either prominent lymphoepithelial lesions, moderate cytologic atypia, or Dutcher bodies, AJSP 1990;14:1087
Resembles lymphoma clinically
Associated with gastric ulceration and extensive fibrosis
Micro: reactive germinal centers, mixed inflammatory cells, polyclonal immunoglobulins
Anaplastic large cell lymphoma
Case report of post-transplant tumor, Archives 2003;127:349
Positive stains: CD30, rarely keratin (AJSP 1996;20:346)
Diffuse large B cell lympoma
Usually > age 50
5 year survival is 60% (related to stage)
May have MALT or non-MALT origin, but both morphologically similar; MALT origin have lymphoepithelial lesions or follicular colonization, non-MALT includes CD10+ follicular lymphoma
Case report of coexistence with two early gastric carcinomas, Archives 1989;113:419
Favorable prognostic factors: scattered lymphocytes (not compact clusters representing 10%+ of tumor), low grade component, lymphoepithelial lesions, AJSP 2001;25:95; CD10+, bcl6+; AJSP 2000;24:1641
Gross: large polypoid or lobulated mass with superficial or deep ulceration; often in distal stomach, but sparing pylorus
Micro: centroblast like cells, multinucleated forms may resemble Reed-Sternberg cells
Positive stains: bcl6 (variable), CD10 (variable), CD35 (variable), keratin (rare, AJSP 1996;20:346)
References: AJSP 2003;27:790
DD: undifferentiated carcinoma (continuity between tumor cells and epithelium, acinar pattern, muscularis mucosa destruction, positive for keratin, mucin)
Very rare as primary site of disease
Criteria for primary: bulk of disease in stomach despite the presence of disease in adjacent lymph nodes; absence of superficial or mediastinal lymphadenopathy; absence of organomegaly or bone marrow involvement by lymphoma; and normal results on complete blood count and differential
Confirm presence of Reed-Sternberg cells as CD15+, CD30+, CD20-, CD45-
Case reports at Archives 2002;126:1534, Archives 1995;119:163
Indolent; when it spreads, tends to involve other mucosal sites such as Waldmeyer’s ring
Develops in background of H. pylori infection or rarely post-transplant (usually low grade, EBV-, mean 7 years after transplant, AJSP 2000;24:100)
Arises from post-germinal center memory B cells (usually bcl6 and CD10 negative)
May arise as oligoclonal proliferations with separate lesions composed of different clones, dominant clones then appear and may disseminate to other lesions, Mod Path 2001;14:957
Rarely have simultaneous gastric MALT and carcinoma, often with associated H. pylori gastritis, AJSP 1997;21:505
Case report of MALT and histiocytic lymphoma of stomach, AJSP 1996;20:1406
Case report of gastric MALT, thymic MALT and Sjogren’s syndrome, Archives 2000;124:770
Treatment: treat H. pylori gastritis (note: may have positive serology even if H. pylori negative by histology, Mod Path 1999;12:1148); also radiation therapy
Micro: dense, monotonous population of centrocyte-like cells, often with residual germinal centers and lymphoepithelial lesions; may have plasmacytoid differentiation; commonly lymphoepithelial lesions (infiltration of glandular epithelium by lymphocytes) or follicular colonization
Signet-ring epithelial cells present in 1/3 in superficial lamina propria associated with lymphoid areas, may represent lymphoepithelial lesions, AJSP 1996;20:588
Positive stains: bcl-6 (some high grade tumors, but <75% of cells, AJSP 2003;27:790), CD10 (variable)
Negative stains: bcl6 (low grade tumors)
Molecular: trisomy 3 by FISH (Hum Path 1999;30:706); PCR has false positives as gastritis contains monoclonal B cells, Mod Path 1999;12:885
DD: benign lymphocytic proliferation (no lymphoepithelial lesions, no Dutcher bodies, no atypia, no monoclonality by PCR)
References: AJSP 1992;16:130
Case report at Archives 1991;115:603
Micro: larger cells than small lymphocytes with cleaved nuclei
Positive stains: CD5
Negative stains: CD23
Rare
Case report of primary gastric HTLV-1 related tumor and peripheral T cell lymphoma at Archives 1994;118:547
Stromal/other tumors
Malignant spindle cell component with benign glandular component
Case report at Archives 1993;117:299
Micro: benign tubular and cystic glands within sarcomatous stroma
Positive stains: epithelial elements - keratin, stromal elements - vimentin and desmin
Case report of 67 year old man with gastric tumor after partial gastrectomy for ulcer, AJSP 1991;15:399
Micro: large eosinophilic cells in alveolar pattern, PAS+ intracytoplasmic granules / crystals
Very rare as stomach primary
Present with GI bleeding and gastric mass
May be pure, accompany adenocarcinoma or be associated with nontrophoblastic gonadal tissue
Aggressive, mean survival less than 1 year whether treated or untreated
Case report in 36 year old woman, Archives 2001;125:1601
Positive stains: smooth muscle actin, vimentin, laminin, type 4 collagen
References: AJSP 1981;5:333
Case report of elastofibroma surrounding an ulcer in 69 year old woman with bilateral subscapular elastofibromas, AJSP 1985;9:233
Gross: gray-white thickened submucosal layer, rubber elastic consistency
Micro: abundant acellular collagen fibers containing numerous elastic, thick, serrated fibers and globules
Follicular dendritic cell sarcoma
Extremely rare
Case report of submucosal tumor at Archives 2000;124:1693
Behaves like intermediate-grade soft tissue sarcoma
Micro: fascicular or storiform patterns of spindle and epithelioid tumor with individually scattered and perivascular aggregates of lymphocytes; cells have indistinct cell borders / syncytial appearance
Positive stains: CD21, CD23, CD35
Negative stains: CD31, CD34, c-kit, HMB45
DD: GIST (less eosinophilic cytoplasm, c-kit+), leiomyosarcoma, MPNST, sarcomatoid carcinoma (usually fungating mass, keratin+, CD21-, CD23-, CD35-)
Gastrointestinal autonomic nerve tumor (GANT)
Rare mesenchymal tumor, ultrastructurally has features of autonomic nervous system
Common in small intestine and stomach
Mean age 64 years
Often has malignant behavior
Poor prognostic factors: size >10 cm, > 5 mitotic figures/10 HPF
Rarely are multiple, usually associated with MEN2b/3, Carney’s triad or neurofibromatosis 1
Need EM for diagnosis
Gross: mean 10 cm, but may be < 6 cm; well circumscribed, tan-pink, soft, often hemorrhagic
Micro: plump spindle cells and round epithelioid cells with abundant pale pink cytoplasm, indistinct borders, growing in whorled, fasciculated, storiform or palisaded patterns; may have skenoid fibers, myxoid background, vascular hyalinization; variable mitotic activity (0 to 23/10 HPF)
May have marked inflammatory infiltrate with peripheral lymphoid cuffing, scattered plasma cells and foam cells
Positive stains: vimentin, CD117/c-kit, CD34 (usually), S100 (20%)
Negative stains: actin, desmin
EM: complex interdigitating cell processes with bulbous synaptic terminals, small, dense core neurosecretory granules (uniform, 190 nm, submembrane spaces), rudimentary cell junctions, intermediate filaments
Molecular: GIST specific c-kit mutations often present
References: AJSP 2001;25:979, AJSP 1996;20:325, AJSP 1993;17:887, Archives 1986;110:309
Gastrointestinal stromal tumor (GIST)
Arise from interstitial cell of Cajal, which are involved in gut pacemaker activity to regulate peristalsis
Stomach is site of origin of 2/3 of GISTs
Initial report suggesting possible neural origin by Mazur and Clark, AJSP 1983;7:507
Symptoms: abdominal pain, melena
Case report of malignant GIST with secondary amyloidosis, Archives 2003;127:470
Simultaneous stomach GIST and adenocarcinoma/carcinoid have been reported, Archives 2000;124:682
Case report of multiple GIST tumors, carcinoid tumor and lipoma, Archives 2001;125:318
Poor prognostic factors: 7 cm+ in size, high cellularity, mucosal invasion, high nuclear grade, 5+ MF/50 HPF (in most cellular part of tumor), myxoid background or lack of stromal hyalinization; can use as individual factors, but by themselves, can’t separate benign from malignant; use histologic patterns below
Micro:
Benign cellular spindle cell pattern: cellular proliferation of bland spindled cells with pale to eosinophilic fibrillar cytoplasm; minimal pleomorphism; cells in whorls or short intersecting fascicles, with frequent and prominent nuclear pallisading, numerous perinuclear vacuoles that indent nucleus, often extensive stromal hyalinization
Benign epithelioid cell pattern: predominantly sheets of epithelioid cells, often with a condensed rim of eosinophilic cytoplasm adjacent to the nucleus and peripheral cytoplasmic clearing; well defined cell membranes, round nuclei with small nucleoli; also scattered bizarre or multinucleated cells; epithelioid cells often mixed with plump spindled cells of similar size and nuclear characteristics; frequent stromal liquefaction or hyalinization
Benign mixed cell pattern: mixture of above two patterns
Tumors other than those above considered not benign
Positive stains: CD117/c-kit, CD34, vimentin
References: AJSP 2002;26:705, AJSP 1999;23:82, Hum Path 2002;33:669, Hum Path 2002;33:459, Hum Path 2002;33:478
Most common site in GI tract is stomach; also in distal extremities
50-75% women, median age 55 years (range, 19-90 years)
Present with bleeding (may be life threatening), ulcer symptoms or as incidental findings
Much less common than GISTs
Mesenchymal tumors composed of modified smooth muscle cells representing the neoplastic counterpart of perivascular glomus bodies
Usually benign, may metastasize to liver and cause death, but cannot predict based on histology
Case report of multiple tumors involving stomach wall and perigastric adipose tissue, AJSP 1992;16:291
Gross: median 2 cm (range, 1.1 to 7 cm), usually antral; circumscribed, often with overlying mucosal ulceration and multinodular
Micro: multiple cellular nodules often separated by streaks of gastric smooth muscle; glomus cells are round, sharply demarcated, with cytoplasmic clearing; hyaline and myxoid change often in center of tumors; mildly dilated pericytoma-like vessels; vascular invasion and focal atypia common; 1-4 mitotic figures/50 HPF
Positive stains: smooth muscle actin, calponin, h-caldesmon, net-like pericellular laminin and collagen type 4
Negative stains: desmin, S100, chromogranin, CD117/c-kit, CD34 (usually)
EM: cytoplasm packed with myofilaments with focal condensations; resemble smooth muscle cells
DD: epithelioid GIST (pericellular clearing, polygonal not oval/round, less prominent veins/capillaries), paraganglioma (chromogranin+, synaptophysin+, S100+), carcinoid (less prominent cell borders, coarser chromatin, keratin+, chromogranin+, synaptophysin+), hemangiopericytoma / solitary fibrous tumor (usually not in GI tract, actin-)
References: AJSP 2002;26:301
Solitary or multiple
Langerhans’ cell histiocytosis
Rare, case reports at AJSP 1990;14:489, Archives 1994;118:1232
Gross: multiple, small sessile elevations in stomach
Micro: diffuse collection of large, polygonal cells with oval nuclei containing longitudinal grooves; may occur in discrete clusters resembling granulomas, may have scattered eosinophils or multinucleated giant cells; no prominent nucleoli, mitotic figures rare
Positive stains: S100, CD1a
EM: Birbeck granules, interdigitating cytoplasmic projections
Micro: smooth muscle differentiation
Positive stains: smooth muscle actin, desmin
EM: pinocytotic vesicles, subplasmalemmal dense patches, cytoplasmic microfilaments with focal densities
Usually in submucosa
Malignant fibrous histiocytoma (MFH)
Rare, case report at Archives 1988;112:251
Usually males
Usually pleomorphic storiform pattern
DD: leiomyosarcoma
Leukemia, lymphoma most common
Melanoma, carcinoma tend to be multiple and ulcerated
Metastatic breast and lung carcinomas may resemble linitis plastica
Case reports: Merkel cell carcinoma (Archives 2003;127:367)
Breast carcinoma simulating linitis plastica (Archives 2001;125:567)
Rarer than GIST
Benign, do not recur
Micro: well circumscribed, not encapsulated, with interlacing bundles of spindle cells and collagen, may have nuclear atypia, also inflammatory cells and peripheral cuff of lymphoid aggregates; no mitotic figures, no skenoid fibers, no epithelioid features; may have nuclear pallisading, Verocay bodies, hyalinized vessels
Positive stains: vimentin, S100 (strong), variable GFAP, often PAS+ needle shaped crystalloids
Negative stains: CD34 (may be focally positive), CD117, desmin, actin
Reference: AJSP 1999;23:431
Very rare
Case report at Mod Path 2000;13:68
Rare (<100 cases reported), 80% in male infants, 3 cases reported in adults
Benign; excision is adequate treatment
May originate from pluripotent cells in the gastric wall
Case report at Archives 2001;125:445;
Miscellaneous
Staging (clinical and pathologic)
Only applies to carcinomas
Primary tumor (T)
TX: primary tumor cannot be assessed
T0: no evidence of primary tumor
Tis: carcinoma in situ (i.e. intraepithelial tumor without invasion of lamina propria)
T1: tumor invades lamina propria or submucosa
T2: tumor invades muscularis propria or subserosa
T2a: tumor invades muscularis propria
T2b: tumor invades subserosa (tumor may penetrate muscularis propria with extension into gastrocolic or gastrohepatic ligaments, or into greater or lesser omentum, without perforation of visceral peritoneum covering these structures - still T2; if peroration of visceral peritoneum covering gastric ligaments or omentum - T3)
T3: tumor invades serosa (visceral peritoneum) without invasion of adjacent structures (spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, retroperitoneum)
T4: tumor invades adjacent structures (intramural extension to duodenum or esophagus is classified by depth of greatest invasion in any of these sites, including the stomach)
Regional lymph nodes (N)
NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastases
N1: metastasis in 1-6 regional lymph nodes
N2: metastasis in 7-15 regional lymph nodes
N1: metastasis in 16+ regional lymph nodes
Note: pN0 means all examined lymph nodes are negative, regardless of the total number removed/examined
Distant Metastasis (M)
MX: distant metastasis cannot be assessed
M0: no distant metastasis
M1: distant metastasis
Stage grouping and 5 year survival
Stage 0: Tis N0 M0, 89%
Stage 1A : T1 N0 M0, 78%
Stage 1B : T1 N1 M0 or T2a/b N0 M0, 58%
Stage 2: T1 N2 M0 or T2a/b N1 M0 or T3 N0 M0, 34%
Stage 3A: T2a/b N2 M0 or T3 N1 M0 or T4 N0 M0, 20%
Stage 3B: T3 N2 M0, 8%
Stage 4: T4 N1-3 M0 or T1-3 N3 M0 or any T, any N, M1, 7%
Grossing specimens
For malignant gastrectomy specimens, should assess 15+ lymph nodes
Take sections from resection margins, tumors / lesions, deep margins to tumors, lymph nodes
Tumor type
Histologic grade
Tumor size
Depth of invasion
Anatomic site
Angiolymphatic invasion
Perineural invasion
Margin involvement (proximal, distal, radial)
Lymph node involvement (total involved, total examined)
Other features (gastritis, dysplasia, specific types of infection)
End of Stomach outline