Small bowel (small intestine)

Last revised 17 July 2008

Last major update September 2003

Copyright © 2003-2008, PathologyOutlines.com, Inc.

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See also Ampulla of Vater

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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 syndromeendometriosis, 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

 

 

Primary references

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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

 

Normal anatomy

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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

 

Normal histology

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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/stenosis

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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)

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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

 

Duplication

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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

 

Ehlers-Danlos syndrome

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Defect of collagen synthesis, may cause spontaneous intestinal perforation and hemorrhage; also hyperelasticity of skin and joints

 

Enterogenous cysts

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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

 

Gastroschisis

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Portion of abdominal wall fails to form together, with extrusion of intestines

 

Heterotopic gastric mucosa

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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)

 

Heterotopic pancreas

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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, #2ductal 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

 

Hirschsprung’s disease

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Originates in colon, but may extend into small bowel, causing enterocolitis and high mortality

See complete discussion under colon

 

Malrotation

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From improper embryologic rotation of gut

 

Meckel’s diverticulum

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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

 

Meconium peritonitis

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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 cavitysmall 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)

 

Omphalocele

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Abdominal musculature fails to form

Infant born with herniated abdominal contents into ventral membranous sac

 

 

Patterns of abnormal small bowel architecture

Severe villous abnormality

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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

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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

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Various villus abnormalities, usually not flat mucosa

Usually due to partial treated celiac sprue

 

 

Malabsorption

Malabsorption-general

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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

 

Abetalipoproteinemia

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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

 

Acrodermatitis enteropathica

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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

 

Agammaglobulinemic sprue

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No plasma cells in lamina propria

 

Celiac sprue

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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

 

Dermatitis herpetiformis

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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

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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

 

Intestinal lymphangiectasia

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Dilated lymphatic channels cause protein-rich fluid in lamina propria and then into gut lumen, causing protein-losing enteropathy

 

Microvillus inclusion disease

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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

 

Refractory sprue

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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

 

Tropical sprue

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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

Duodenal peptic ulcer

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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

 

Marginal ulcer

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Associated with gastrojejunostomy opening, usually in jejunum distal to stoma

 

Small bowel ulcer

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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

Autoimmune enteropathy

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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

 

Behcet’s disease

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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

 

Collagenous enterocolitis

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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

 

Crohn’s disease

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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