Small bowel (small intestine)
Last revised 17 July 2008
Last major update September 2003
Copyright © 2003-2008, PathologyOutlines.com, Inc.
See also Ampulla of Vater
Bold and underlined topics are hypertext links-may open a new window
Table of Contents
Primary references, normal anatomy, normal histology
Congenital anomalies: atresia/stenosis, diverticula (not Meckel’s), duplication, Ehlers-Danlos, enterogenous cysts, gastroschisis, heterotopic gastric mucosa, heterotopic pancreas, Hirschsprung’s, malrotation, Meckel’s diverticulum, meconium peritonitis, omphalocele
Patterns of abnormal architecture: severe villous, variable villus, nonspecific variable villus
Malabsorption: general, abetalipoproteinemia, acrodermatitis enteropathica, agammaglobulinemic sprue, celiac sprue, dermatitis herpetiformis, disaccharidase deficiency, intestinal lymphangiectasia, microvillus inclusion disease, refractory sprue, tropical sprue
Ulcers: duodenal peptic ulcer, marginal ulcer, small bowel ulcer
Inflammatory disorders: autoimmune enteropathy, Behcet’s disease, collagenous enterocolitis, Crohn’s disease, duodenitis, enterocolic (lymphocytic) phlebitis, eosinophilic enteritis, graft vs. host disease, ileal pouch/pouchitis, jejunitis, lymphocytic enterocolitis, malakoplakia, necrotizing enteritis, radiation enterocolitis, sarcoidosis, Torkelson syndrome, ulcerative colitis
Infectious disorders: diarrhea and dysentery, bacteria, AIDS, Anisakis, Campylobacter, Capillariasis, Clostridium, CMV, Cryptosporidium, Cyclospora, Entamoeba histolytica, E coli, Giardia, Isospora, Leishmaniasis, Microsporidiosis, Mycobacteria, Salmonella, Strongyloides, Vibrio, Whipple’s disease, Yersinia
Obstruction: general, adhesions, chronic idiopathic pseudo-obstruction, hernias, scleroderma, volvulus
Other/benign tumors or tumor-like conditions: adenoma, amyloidosis, barium granuloma, blue rubber bleb nevus syndrome, brown bowel syndrome, Brunner’s gland hamartoma, Brunner’s gland nodule, clofazimine, colchicine toxicity, common variable immunodeficiency syndrome, Cowden’s syndrome, Cronkite-Canada syndrome, endometriosis, enteritis cystica profunda, fibromatosis, gangliocytic paraganglioma, ganglioneuroma, hemangioma, hemorrhagic necrosis, hereditary telangiectasia, hyperplastic Pacinian corpuscle, idiopathic retractile mesenteritis, idiopathic retroperitoneal fibrosis, inflammatory fibroid polyp, inflammatory myofibroblastic tumor, inflammatory polyp, intussusception, ischemia, kayexelate, Klippel-Trenaunay-Weber syndrome, leiomyoma, lipoma, lymphangiectasia, lymphangioma, lymphoid hyperplasia, mastocytosis, myxoma, neurofibroma, neuromuscular and vascular hamartoma, Peutz-Jeghers polyp, pneumatosis cystoids intestinalis, pseudomelanosis duodeni, radiation effect, reactive nodular fibrous pseudotumor, sclerosing peritonitis, selective IgA deficiency, transplantation, tufting enteropathy, Turner’s syndrome, vascular disease, vasculitis
Carcinoma: general, adenocarcinoma, adenosquamous, anaplastic, neuroendocrine, signet ring, small cell
Lymphoma: general, Burkitt’s, diffuse large B cell, follicular, histiocytic, Hodgkin’s, lymphoplasmacytic, MALT, mantle cell, Mediterranean, natural killer cell (NK), post-transplant, primary effusion, sprue-associated, Waldenström macroglobulinemia
Other malignancies: carcinoid tumor, carcinoid syndrome, duodenal endocrine tumors, follicular dendritic cell sarcoma, GANT, GIST, granulocytic sarcoma, Kaposi’s sarcoma, leiomyosarcoma, metastases, mullerian adenosarcoma, Zollinger-Ellison syndrome
Miscellaneous: staging, features to report
American Journal of Surgical Pathology (AJSP), Jan 2000 to Sep 2003
Archives of Pathology and Lab Medicine (Archives), Jan 1999 to Sep 2003
Human Pathology (Hum Path), Jan 2000 to July 2003
Modern Pathology (Mod Path), Jan 2000 to Aug 2003
AJCC Cancer Staging Manual (6th Ed)
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
6 meters long, divided into duodenum, jejunum, ileum
Duodenum: 25 cm long, from pyloric sphincter to ligament of Treitz, mostly retroperitoneal, fixed in position
Jejunum: 240 cm long, 40% of remainder of bowel, begins at ligament of Treitz
Ileum: 360 cm long, distal 60% of post-duodenal bowel
Mucosa has transverse folds, prominent in proximal ileum, flat/absent at terminal ileum
Gross images: mesentery/serosa, terminal ileum
Peyer’s patches: oval, in antimesenteric side of terminal ileum, represent lymphoid follicles
Ileocecal valve: at end of small bowel; 2 lip structure containing adipose tissue and lymphoid tissue
Lymph nodes: duodenum drains to portal and pyloric nodes; jejunum and proximal ileum drains to mesenteric nodes and nodes around superior mesenteric artery, terminal ileum drains to ileocolic nodes
Intestinal immune system
Peyer’s patches in ileum
M cells (membranous) in small bowel and colon, which transfer antigen macromolecules from lumen to lymphocytes
T cells, usually CD8+ are scattered in surface epithelium
Lamina propria contains CD4+ T cells and B cells
Mucosa associated lymphoid tissue: lymphoid nodules, mucosal lymphocytes, appendiceal lymphoid follicles and mesenteric nodes
Neuromuscular function
Anterograde and retrograde peristalsis mixes food and promotes maximal contact of nutrients with mucosa
Colonic peristalsis prolongs contact with mucosa
Peristalsis is mediated via myenteric plexus and autonomic innervation (sympathetic-thoracolumbar, parasympathetic-vagal); also through interstitial cells of Cajal (pacemaker cells) and smooth muscle cells
top
Layers: mucosa, submucosa, muscularis propria (externa), subserosa, serosa
Mucosa: contains villi with central blood vessels, lymphatics; layers are epithelium, lamina propria, muscularis mucosa
Villi: short and stubby in duodenum, very tall in jejunum, intermediate height in ileum; contain microvilli; villus to crypt length is 3-5:1; contain primarily columnar absorptive cells and goblet cells; usually 1 lymphocyte per 5 enterocytes; villi may be short and distorted next to lymphoid aggregates; 4 normal villi in a row in a biopsy suggests normal villous architecture
Absorptive cells: have microvilli on luminal surface (brush border) and underlying mat of microfilaments (terminal web)
Crypts of Lieberkuhn: lower 20% of epithelium, contain undifferentiated (immature) crypt cells, Paneth cells (have large, apical eosinophilic granules containing antimicrobial proteins), scattered goblet cells and endocrine cells; are surrounded by pericrypt fibroblast sheath; secrete ions, water, IgA, antimicrobial peptides into lumen
Crypt cells take 3-8 days to migrate to surface; allows for rapid repair, but also causes these cells to be sensitive to radiation therapy and chemotherapy
Lamina propria: contains loose connective tissue, lymphocytes, plasma cells, occasional eosinophils, macrophages, mast cells, neutrophils
Submucosa: contains connective tissue, blood vessels, lymphatics, submucosal (Meissner’s) plexus; also Brunner’s glands in duodenum
Brunner glands: submucosal mucous glands in duodenum, secrete bicarbonate ions, glycoproteins, pepsinogen II; resemble gastric pylorus mucous glands
Muscularis propria (externa): inner circular and outer longitudinal layer, with myenteric (Auerbach’s) plexus between these layers; plexus also contains interstitial cell of Cajal, ganglion cells, fibroblasts
Serosa: contains mesothelial lining, loose connective tissue
Endocrine cells: similar to cells in pancreas, biliary tree, lung, thyroid, urethra; contain fine eosinophilic granules with secretory proteins; nuclei on luminal side of granules, not basal
Micro images: villi, jejunum, enterocyte, serosa
Reference: AJSP 2003;27:228
Congenital anomalies
Atresia: imperforate mucosal diaphragm or string like segment of bowel
Case report of multiple areas of jejunal atresia with apple peel deformity (twisted around an artery) associated with 22q11 abnormality, Archives 2000;124:880
Stenosis: narrowing of lumen; less common
Causes: developmental failure, intrauterine vascular accidents, intussusceptions
Complications: perforation, meconium peritonitis, brown bowel syndrome
Diverticula (other than Meckel’s)
Duodenal: present in 1-2%, usually solitary and congenital, may cause obstructive jaundice, pancreatitis, fistulas, hemorrhage, perforation; usually penetrate the pancreas; may project into lumen like a polyp
Jejunal: present in 0.3% to 1.4% of autopsies; usually proximal jejunum along mesenteric border; often multiple with thin wall; associated with diverticula elsewhere in GI tract; some are congenital but most are acquired; usually asymptomatic but may cause obstruction, hemorrhage, perforation, abscess, malabsorption or Vitamin B12 deficiency, possibly due to bacterial overgrowth in the diverticula
Saccular to long, cystic structures; duplication usually is incomplete due to shared muscular wall
More common in ileum
Rare in duodenum, choledochocele is more common
Not associated with vertebral body abnormalities
Treatment: resect entire duplication and segment of normal bowel attached to it
Defect of collagen synthesis, may cause spontaneous intestinal perforation and hemorrhage; also hyperelasticity of skin and joints
Found in wall of small bowel, mesentery, posterior mediastinum or rectorectal space
May be associated with vertebral body abnormalities
Micro: lined by respiratory, small intestinal or gastric epithelium; wall composed of irregularly oriented smooth muscle
Portion of abdominal wall fails to form together, with extrusion of intestines
Mature gastric tissue in location where normally not found (i.e. small bowel)
Discrete small nodules or sessile polyps, usually in duodenum
May cause obstruction, diarrhea, ulceration, bleeding, perforation, intussusception, pain (Pediatr Dev Pathol 2000;3:277)
Presence in duodenum is associated with H. pylori infection and is probably not congenital (Hum Path 2003;34:156)
Case reports: Case of the Week #124; jejunal mass (Archives 2003;127:506), associated with gastric type adenoma (Virchows Arch 1999;435:452)
Gross images: #1; #2; #3; #4; #5
Micro: mature gastric tissue, usually fundic type mucosa with chief and parietal cells, lined by foveolar epithelium, with a full mucosal thickness, forming a mucosal island.
Micro images: #1; #2; #3; #4; #5
DD: gastric metaplasia (associated with chronic inflammation, duodenitis and H. pylori, only occupies part of mucosal thickness, typically no gross findings, no parietal cells, Braz J Med Biol Res 2007;40:897, Dig Liver Dis 2002;34:16), peptic ulcer disease (no goblet cells)
Also called adenomyoma, myoepithelial hamartoma (although without pancreatic tissue)
Incidence of 1-14%
Most common near ampulla of Vater; also stomach, jejunum
May cause blockage of duct, leading to infection, cystic dilation and fat necrosis
Usually encountered incidentally at surgery, submitted for frozen section
Case reports of associated carcinoma, Archives 1999;123:707, acinar cell#1, #2, ductal adenocarcinoma
Gross: submucosal nodule, intramural mass; yellow-white, lobulated, 0.2 cm to 4 cm; may have central mucosal dimple
Micro: pancreatic ducts and acini with smooth muscle proliferation but without islets
Originates in colon, but may extend into small bowel, causing enterocolitis and high mortality
See complete discussion under colon
From improper embryologic rotation of gut
Persistence (failure to involute) of proximal vitelline duct (aka omphalomesenteric duct, connects lumen of fetal intestine to yolk sac)
Normally, vitelline duct atrophies and becomes fibrous cord connecting umbilicus and bowel, which is subsequently absorbed
Found in 2% of normal population, usually asymptomatic, 63% males
Usually 20 cm proximal to ileocecal valve on antimesenteric side of bowel, 1-8 cm long
Associated with other congenital anomalies
Case report with involvement of Crohn’s disease and pancreatic heterotopia, Archives 2003;127:E99, micro image
Complications: perforation, enteroumbilical fistula, peptic ulceration (usually in adjacent ileum and not in diverticulum), hemorrhage (often massive in children), intussusception, obstruction, carcinoid and other tumors
Treatment: remove if found at surgery, even if incidental
Gross images: image1, image2, image3
Micro: usually small intestinal mucosa, but 50% have gastric or pancreatic heterotopia; contains all 3 layers of bowel wall
Rare prenatal complication in 1 per 30K live births
GI perforation releases meconium into abdominal cavity, inducing sterile inflammatory reaction and calcium deposition
Perforation may be due to meconium ileus, atresia, stenosis, internal hernia, Hirschprung’s disease, volvulus, congenital bands, anoxia leading to bowel ischemia or idiopathic
Presents with fetal distress, maternal polyhydramnios, abdominal distention or a mass
Newborns with perforation should be evaluated for cystic fibrosis (Pediatr Surg Int 2003;19:75)
Radiology: prenatal ultrasound shows dilated bowel, ascites, polyhydramnios, intra-abdominal calcifications (Prenat Diagn 2005;25:676); ultrasound findings have prognostic value (Fetal Diagn Ther 2003;18:255, Prenat Diagn 2007;27:960)
Case reports: Case of the Week #106
Treatment: surgical; gestational age at diagnosis does not predict postnatal outcome (J Pediatr Surg 1995;30:979)
Gross: organized peritonitis with fibrosis, calcifications, dense intestinal adhesions; meconium pseudocyst (fibrous wall) may form
Gross images: abdominal cavity; small intestine
Micro: peritoneal surface shows fibrinous exudate with microcalcifications, bile pigment-like debris, histiocytes, chronic inflammatory cells
Micro images: peritoneal surface #1; #2
DD: vernix caseosa peritonitis (cheesy white exudate coats the visceral organs after cesarean section, J Obstet Gynaecol 2007;27:660)
Abdominal musculature fails to form
Infant born with herniated abdominal contents into ventral membranous sac
Patterns of abnormal small bowel architecture
Flat intestinal mucosa with no villi seen; usually diffuse, with epithelial lymphocytosis, crypt hyperplasia, numerous mitotic figures
Mucosa actually of normal villous thickness
Due to celiac sprue, refractory or unclassified sprue, other protein allergies, lymphocytic enterocolitis
Variable villus abnormality and crypt hypoplasia
Villi focally flat or mild/moderate villus shortening
Also increased intraepithelial lymphocytosis, decreased crypt mitotic figures
Causes: marasmus (severe protein-calorie malnutrition), kwashiorkor (protein malnutrition but adequate caloric intake), megaloblastic anemia (vitamin B12 and folate deficiency, no increased inflammatory cells), chemoradiation effect (apoptosis, atypical cells), microvillus inclusion disease
Nonspecific variable villus abnormality
Various villus abnormalities, usually not flat mucosa
Usually due to partial treated celiac sprue
Malabsorption
Standard site for biopsies is proximal jejunum, just distal to ligament of Trietz
Mount specimen mucosal side up on solid substance, then embed perpendicular to mounting material; then step section or serial section
Small bowel is important for absorption of fats, fat-soluble vitamins, proteins, carbohydrates, electrolytes, minerals, water
Symptoms, due to deficiency in ( ): diarrhea, flatus, abdominal pain, weight loss, mucositis, anemia (iron, folate, Vitamins B6, B12), bleeding / purpura (Vitamin K), osteopenia, tetany (calcium, magnesium, vitamin D), amenorrhea / impotence / infertility (generalized malnutrition), hyperparathyroidism (calcium, vitamin D), edema (albumin), dermatitis (zinc, vitamin A, fatty acids, niacin), peripheral neuropathy (vitamins A, B12)
Steatorrhea: bulky, greasy stools associated with weight loss, anorexia, muscle wasting
In US, most common malabsorption disorders are celiac sprue, pancreatic insufficiency and Crohn’s disease
Physiologic classification of malabsorption - due to disturbances of:
(a) Intraluminal digestion (saliva, gastric peptic digestion, small bowel, bile salts)
(b) Terminal digestion (hydrolysis of carbohydrates and peptides by disaccharidases and peptidases in brush border of small bowel)
(c) Transepithelial transport (across small bowel epithelium to intestinal vasculature); fatty acids to triglycerides, cholesterol to chylomicrons
(a) Causes of defective intraluminal digestion
Digestion of fats/proteins: pancreatic insufficiency due to pancreatitis or cystic fibrosis, Zollinger-Ellison syndrome
Defective bile secretion (fat solubilization): ileal dysfunction or resection with decreased bile salt uptake, cessation of bile flow (obstruction, hepatic dysfunction), nutrient preabsorption or modification by bacterial overgrowth
(b/c) Causes of abnormalities in terminal digestion or transepithelial transport
Disaccharidase deficiency (lactose intolerance), bacterial overgrowth, abetalipoproteinemia, defects in ileal bile acid transporter
Rare inborn error of metabolism, autosomal recessive
Due to defect in synthesis and export of apoprotein B from intestinal mucosal cells; free fatty acids and monoglycerides cannot be assembled into chylomicrons and become triglycerides stored within cells, causing lipid vacuolization
Laboratory: lipid profile shows no chylomicrons, no VLDL, no LDL; CBC smear shows acantholytic red blood cells (Burr cells) due to lipid membrane abnormalities
Symptoms: failure to thrive, diarrhea, steatorrhea
Micro: marked fat vacuoles in apical villous cytoplasm, villi normal
Positive stains: fat stains highlight lipid vacuoles
DD: megaloblastic anemia, celiac sprue, tropical sprue have similar vacuolar change
Autosomal recessive, linked to zinc deficiency, affects children
Cutaneous lesions (perioral and extremity skin lesions, alopecia, nail dystrophy), diarrhea, malabsorption
Treatment: zinc sulfate
Micro: severe villus abnormality in some; normal in others
EM: rodlike fibrillar inclusions in Paneth cells
No plasma cells in lamina propria
Also called nontropical sprue, gluten-sensitive enteropathy, celiac disease
Individuals with a genetic predisposition have increased immunological responsiveness to prolamins such as dietary wheat gliadin and similar proteins in barley, rye, possibly oats
Gluten is an alcohol soluble, water insoluble protein component in wheat, oat, barley, rye
Disease is due to abnormal cell mediated immunity, perhaps associated with adenovirus infection (cross reactivity to E1b protein of type 12 adenovirus); gluten exposure causes accumulation of intraepithelial cytotoxic T cells and helper T cells in lamina propria
Major cause of malabsorption; almost all adults in North America with severe villous abnormality and crypt hyperplasia have celiac sprue
Improves clinically and microscopically after withdrawal of wheat gliadins and related grain proteins from diet
Affects 1 per 200-300 whites in Western countries, onset typically in childhood, rare in Africa, Japan, China
HLA DQ alpha/beta heterodimer appears to confer susceptibility (90% have DQw2 HLA on #6), linked to HLA B8 (80%)
Also associated with lymphocytic gastritis / colitis, selective IgA deficiency, type 1 diabetes, Sjogren’s syndrome, autoimmune thyroiditis
Symptoms: diarrhea and failure to thrive in newborns; or symptoms of diarrhea, flatulence, weight loss, fatigue beginning as late as age 40
Late onset: 40’s and 50’s; symptoms of short stature, infertility, peripheral neuropathy, iron or folate deficiency, osteoporosis, indigestion, dental enamel defects
Labs: elevated serum IgA except in those with IgA deficiency (more common in these patients than normals); also IgA anti-transglutaminase, antiendomysial, antireticulin and antigliadin antibodies
Serum IgA: used to monitor compliance with gluten-free diet
Antitransglutaminase antibody: sensitive marker of disease
IgA anti-endomysial antibody: detect with monkey esophageal tissue; sensitive and specific, although also positive in dermatitis herpetiformis
IgA and IgG anti-gliadin antibody: less sensitive than antitransglutaminase and antiendomysial antibodies
Anti-reticulin antibody: in 40%, but nonspecific; also seen in Crohn's disease, myasthenia gravis, Sjogren’s, other
Diagnosis: antitransglutaminase or antigliadin or antiendomysial antibodies plus clinical malabsorption plus typical histologic findings plus improvement in symptoms and histology after gluten withdrawal
Complications: long term risk of malignant disease is 2x normal, usually T cell intestinal lymphomas; also GI or breast carcinomas or esophageal squamous cell carcinoma
Gross: usually flat, scalloped mucosa; may be normal
Micro: increase in intraepithelial lymphocytes (initial and most sensitive marker, 40+ lymphocytes per 100 surface or upper crypt enterocytes; early-clustering of 12+ lymphocytes at tip of villi and extending evenly down the sides of the villus); diffuse enteritis with marked atrophy or total loss of villi; fat globules in surface epithelium, enterocytes have stratified nuclei, lose their brush border, increased crypt mitotic figures; crypts are elongated and hyperplastic, but overall mucosal thickness is the same
Also increase in plasma cells in lamina propria; changes more marked in proximal small bowel (greater exposure) and abnormalities recede last here after gluten withdrawal; neutrophils, if present, are not prominent
Note: pathology report can only say consistent with celiac sprue
Micro images: image1, image2, image3, image4, image5
Micro virtual slide: image1
DD: severe tropical sprue (no antiendomysial antibodies, responds to antibiotics and folate), dermatitis herpetiformis (associated with gluten-sensitive enteropathy but also has skin lesions), infectious enteritis (prominent neutrophils, normal intraepithelial lymphocytes), kwashiorkor, common variable immunodeficiency (no plasma cells, marked lymphoid hyperplasia, often Giardia infection), other protein allergies (sprue symptoms with disappearance and reappearance if offending substance is withdrawn / reintroduced), Crohn’s disease, autoimmune enteropathy (crypt injury or destruction, anti-enterocyte antibodies, typically within first 6 months of life)
References: Mod Path 2003;16:342
Resembles celiac sprue - both respond to gluten free diet (skin lesions improve), both associated with HLA-B8 and HLA-DR3, both associated with lymphoma
Pruritic, papulovesicular lesion symmetrically distributed on scalp, buttocks, extremities, with granular deposition of IgG at epidermal-dermal junctional
Micro: severe mucosal lesion on small bowel biopsy; may be patchy with variable villus abnormality
Disaccharidase (lactase) deficiency
Disaccharidases are located in apical cell membrane of villous absorptive epithelial cells
Congenital deficiency: rare; malabsorption evident with milk feeding, which causes explosive, watery, frothy stools and abdominal distention
Acquired deficiency: common in North American blacks; causes osmotic diarrhea
Diagnosis: increased hydrogen in breath test due to bacterial fermentation of undigested lactose
Treatment: terminate milk and milk products
Dilated lymphatic channels cause protein-rich fluid in lamina propria and then into gut lumen, causing protein-losing enteropathy
Also called congenital or familial microvillous atrophy
Disorder of intestinal brush border that causes intractable watery diarrhea with steatorrhea in infants
Patients require total parental nutrition, and rarely live beyond age 2 years
Villous atrophy may be due to apoptotic cell loss, Hum Path 2000;31:1404
Treatment: small bowel transplant
Micro: severe villous abnormality with crypt hypoplasia, resembling celiac sprue but without lymphocytosis; increased enterocyte apoptosis and proliferation
Positive stains: CD10, PAS, polyclonal CEA, alkaline phosphatase (cytoplasmic staining vs. linear brush border staining in normals); vacuoles - PAS, CEA
EM: abnormal microvillus structures at luminal border of enterocytes; apical intracytoplasmic inclusions lined by microvilli
References: AJSP 2002;26:902
Also called unclassified sprue
Celiac sprue that does not respond to gluten free diet; may be due to lymphoma
Note: wheat is present in many foods, so must ensure that diet is really gluten free
Associated with cavitation of mesenteric lymph nodes and hyposplenism
Collagenous sprue: patchy, excessive subepithelial collagen deposit in some of these patients (5/10 in one study); may eventually respond to gluten-free diet, but disease may also be fatal
DD: lymphoma
References: AJSP 2000;24:676
Also called post-infectious sprue
Affects people living in or visiting the tropics, particularly Caribbean (not Jamaica), Africa, India, SE Asia, Central/South America
Has endemic and epidemic features
May be due to E. coli or Haemophilus
Symptoms: malabsorption within weeks of acute diarrheal enteric infection
Treatment: broad-spectrum antibiotics (tetracycline), folic acid, vitamin B12
No increased risk of intestinal lymphoma
Micro: variable villous atrophy (none, partial, total); injury to entire small bowel (not proximal as in celiac sprue), inflammatory infiltrate, crypt hyperplasia
Ulcers
Decreasing incidence, but still common
Imbalance between gastric acid production and protective factors of intact epithelium and bicarbonate production
Increased gastric acid production requires intact fundic mucosa; associated with duodenal Helicobacter pylori and gastric metaplasia; not associated with malignancy
Treatment: H2 blockers; 80% heal within a month; surgery if hemorrhage, perforation, obstruction or failure to respond to medical treatment
Gross: usually single lesion within 2 cm of pylorus; multiple lesions throughout duodenum suggest Zollinger-Ellison syndrome; margins well defined; no heaped up edges; may have large vessel with open lumen at ulcer base; also fibrosis and shortening of duodenum
Gross images: image1
Micro: ulcer usually < 1 cm, circular, small; brown ulcer base (digested blood), no induration of margins of ulcer; abrupt lesions with normal adjacent mucosa; no scarring or blood vessel thickening; gastric metaplasia and chronic duodenitis common; various villus abnormality in proximal duodenum with active duodenitis; also Brunner’s gland hyperplasia; Helicobacter pylori often present
Associated with gastrojejunostomy opening, usually in jejunum distal to stoma
Almost always related to other gastroduodenal disease
Associated with obstruction, perforation, hemorrhage
Causes: congenital anomalies, mechanical disorders, vascular occlusions, radiation, celiac disease, endometriosis, tumors, specific inflammations, medication (NSAIDs, enteric-coated potassium and hydrochlorothiazide)
Gross: ulcer with adjacent hemorrhage, congestion, edema
Micro: nonspecific changes
Inflammatory disorders
Intractable watery diarrhea syndrome in infants
Associated with antibodies to intestinal epithelial cells
Usually severe and intractable, requiring total parenteral nutrition
Similar condition in adults associated with variable immunodeficiency and type I diabetes, rheumatoid arthritis, hemolytic anemia
Treatment: immunosuppressive agents
Micro: variable villus abnormality, few intraepithelial lymphocytes; may have colitis
GI involvement in 10% of cases, usually ileum and cecum
Punched out ulcers that may perforate; perivascular inflammation and necrotizing vasculitis often present
Also aphthous stomatitis, genital ulcers, relapsing iritis
High intraepithelial lymphocyte count in terminal ileum biopsies of affected patients, Mod Path 2003;16:115, AJSP 2002;26:1484
Lymphocytes are mostly suppressor T cells
Symptoms: chronic nonbloody diarrhea, relatively normal endoscopy
Micro images: image1
Positive stains: trichrome
Also called terminal ileitis, regional enteritis, granulomatous colitis
Relapsing, discontinuous, transmural granulomatous disease from oral cavity to anus, usually involves small intestine and colon
Affects primarily Western populations, equal gender incidence; 3 per 100,000, peaks in teens/twenties and 50/60’s; RR: Whites 2-5:1; Jews 3:1; associated with smoking
Monozygotic twins have 30-50% concordance
Cause unknown, although recent study found Yersinia DNA in 30% of cases by PCR, AJSP 2003;27:220; may be due to alteration in steady state between immune system activation by microbes, antigens, endogenous inflammatory stimuli and host defenses that maintain integrity of mucosa and down-regulate inflammation
Symptoms: variable, including episodic mild diarrhea, fever, pain; may be precipitated by stress; if colon affected, may have anemia
20% have abrupt onset, resembling acute appendicitis or bowel perforation
Extraintestinal symptoms: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, clubbing of fingertips, primary sclerosing cholangitis (not as common as with ulcerative colitis); occasionally uveitis, pericholangitis, renal disorders secondary to periureteral fibrosis
Complications: fibrosing strictures (common in terminal ileum), fistulas to loops of bowel, bladder, vagina, perianal skin; also protein losing enteropathy, generalized malabsorption, vitamin B12 deficiency, bile salt malabsorption with steatorrhea, perforation, abscesses; 5x risk for GI carcinoma, usually adenocarcinoma of ileum
Carcinoma: small bowel - mean 20 years after onset of Crohn’s, usually ileum or site of active disease; often in strictures, poorly differentiated, poor prognosis; 25% in bypassed bowel loops; dysplasia in adjacent epithelium
colon - mean 20 years after diagnosis, usually gross intraluminal lesion, 20% in bypassed rectum; better differentiated and better prognosis than small bowel carcinomas; dysplasia near and distant from tumor
Sites: small bowel only (particularly terminal ileum)-40%, colon only-30%; rarely other sites in GI tract
Course: progressive, only rarely regresses
Treatment: medical (immunosuppressive therapy), surgical
Gross: serosa dull and granular with creeping fat (mesenteric fat wraps around bowel surface), thick/rubbery intestinal wall (due to edema, inflammation, fibrosis, hypertrophy of muscularis propria), narrow lumen (string sign on barium enema), sharp demarcation of affected from uninvolved bowel, fistulas; no rectal involvement
Early - aphthous mucosal ulcers that coalesce into long, serpentine linear ulcers along bowel axis with cobblestone appearance
Late - shortened and fibrotic mesentery; prominent reactive lymph nodes
Micro: sharply delimited and typically transmural involvement of bowel by an inflammatory process with mucosal damage, noncaseating, non-confluent, sarcoid-like granulomas (60%) in involved and non-involved bowel, fissuring (30%) deep into muscularis propria with formation of fistulas and strictures; focal neutrophils in epithelium early on, particularly overlying lymphoid aggregates; also plasmacytosis, cryptitis, crypt abscesses; superficial or deep ulceration, edema, lymphatic dilation, hyperplasia / duplication of muscularis mucosa; may have prominent nerve plexuses (submucosal, myenteric); often serositis and thickened bowel wall;
late - architectural distortion (villus blunting), crypt atrophy, particularly in colon, pyloric or Paneth cell metaplasia in distal colon
rarely cystically dilated glands (enteritis cystica profunda)
Areas of stricture may have thick and continuous muscle layer from mucosal base to muscularis propria 1 cm or more in length, called “obliterative muscularization of submucosa”, Archives 2001;125:1331
Micro images – obliterative muscularization - image1, desmin/smooth muscle actin
Micro virtual slide: image1
DD: Crohn’s disease of colon resembles ulcerative colitis (Crohn’s: skip lesions, transmural involvement, deep ulcerations, marked lymphocytic infiltra