Small bowel (small intestine)
Last revised 3 November 2009
Last major update September 2003
Copyright © 2003-2009, 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, duodenum #1, #2, #3
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
Celiac sprue - small bowel chapter
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; 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
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
Does not appear to be associated with H. pylori gastritis (Am J Gastroenterol 2006;101:1880)
Celiac sprue - small bowel chapter (continued)
Symptoms: diarrhea and failure to thrive in newborns; or symptoms of diarrhea, flatulence, weight loss, fatigue beginning as late as age 40
Symptoms include episodic diarrhea, abdominal pain and distention and weight loss (Clin Med Res 2004;2:71), with clinical and microscopic improvement after dietary withdrawal
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
Celiac sprue - small bowel chapter (continued)
Case reports: Case of the Week #127
Treatment: improves clinically and microscopically after dietary withdrawal of wheat gliadins and related grain proteins
Gross: usually flat, scalloped mucosa; may be normal
Micro: increase in intraepithelial lymphocytes, including 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 (Mod Path 2003;16:342); 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 state consistent with celiac sprue
Micro images: image #1; #2; #3; #4; #5
case of the week - small bowel #1; #2
Micro virtual slide: image1
Celiac sprue - small bowel chapter (continued)
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),
▪ common variable immunodeficiency (no plasma cells, marked lymphoid hyperplasia, often Giardia infection),
▪ other protein allergies (sprue symptoms disappear and reappear if offending substance is withdrawn / reintroduced),
▪ Crohn’s disease,
▪ kwashiorkor,
▪ autoimmune enteropathy (crypt injury or destruction, anti-enterocyte antibodies, typically in first 6 months of life)
▪ duodenal intraepithelial lymphocytosis with normal villous architecture, associated with H. pylori infection, but without any other features of celiac disease (Mod Path 2005;18:1134)
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 infiltrate, serositis, granulomas, fissures, fistulas, malabsorption if ileum involved); sigmoid colon diverticular disease; tuberculosis, ischemic bowel disease
Associated with dyspepsia
Micro: increased plasma cells, edema, intraepithelial neutrophils; severe cases have villous atrophy, more neutrophils but fewer plasma cells; gastric metaplasia, Helicobacter pylori may be present
Enterocolic (lymphocytic) phlebitis
Also called lymphocytic or granulomatous or necrotizing phlebitis, myointimal venous hyperplasia
Ischemia and necrosis of ileum or colon due to localized phlebitis associated with fresh or organized thrombus of intramural mesenteric veins
No systemic vasculitis
Associated with hydroxyethyl rutozide, also other drugs
Does not recur after surgery
References: AJSP 2000;24:824
Eosinophilic enteritis / gastroenteritis
Associated with peripheral eosinophilia and allergic symptoms in children or young adults
Nausea, vomiting, diarrhea, steatorrhea, protein-losing enteropathy
Symptoms are related to site of infiltration - mucosa of stomach/small bowel with diarrhea and malabsorption, submucosa and muscularis propria with obstruction, subserosa with ascites
Micro: marked eosinophilic infiltration of bowel wall, prominent vessels, occasionally necrotizing granulomas and vasculitis; eosinophils typically not associated with other inflammatory cells; infiltration may be patchy
DD: Ancylostoma caninum infection, Sarcocystis infection, collagen vascular disease, inflammatory bowel disease, non-Hodgkin’s lymphoma
Associated with bone marrow transplants
Severe watery diarrhea, also changes in skin and liver
Micro: epithelial crypt apoptosis with minimal inflammation; severe cases have sloughing of mucosa
Formed from connecting loops of terminal ileum; for patients requiring total colectomy to create continence in an ileostomy or to preserve anal sphincter function
Pouches are contraindicated in Crohn’s disease, because they are associated with fistulas and abscess
Complications: fistula, obstruction, incontinence, leaks, pouchitis
Pouchitis
Incidence 8% to 46%; some cases are due to initially undiagnosed Crohn’s disease
Nausea, vomiting, malaise, fever, cramping
Increased ileal stool that is bloody, watery, foul smelling; often with altered bacteria
Micro: decreased epithelial cell mucin, few/no lymphoid follicles; ulcers with granulation tissue, cryptitis, crypt abscesses and patchy neutrophils; rarely dysplasia
Treatment: antibiotics, pouch excision
Also called acute phlegmonous jejunitis
Rare, men and women age 55+
Gross: sharply demarcated bowel mucosal inflammation, often with serosal pus; edematous bowel wall, glassy mesentery, enlarged lymph nodes
Micro: lymphangitis, regional lymphadenitis, abscesses within mesentery
Spruelike condition
Refractory spruelike condition associated with colonic mucosal abnormalities
Lymphocytic colitis related
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
Most likely secondary to bacterial infection
Rare in small bowel
Micro: histiocytes contain calcospherites (Michaelis-Gutmann bodies)
Acute, necrotizing inflammation of small bowel and colon
Most common acquired GI emergency of neonates; common in premature or low birth weight infants, particularly when they start on oral foods at 2-4 days
Cause: feeding with immature gut immune system causes release of proinflammatory cytokines; bacteria in food produce more cytokines and injure mucosa; may also be due to deranged intestinal blood flow
Affects terminal ileum, ascending colon
Symptoms: mild GI disturbance or fulminant illness with intestinal gangrene, perforation, sepsis, shock
Complications: short bowel syndrome, malabsorption (due to ileal resection), strictures, recurrence
Treatment: fluids and surgery if gangrene/perforation
Micro: early-mucosal edema, hemorrhage, necrosis; late-hemorrhagic and gangrenous bowel wall, fibrous strictures; pneumatosis cystoides intestinalis often present
Acute - anorexia, cramps, diarrhea due to mucosal injury and malabsorption
Chronic - may present as inflammatory colitis or indolent; vascular injury, ischemic fibrosis, stricture
Micro (chronic): atrophic mucosa, ectatic blood vessels, fibrosis, vascular wall thickening, vascular stenosis
Usually does NOT involve the small bowel
Should rule out Crohn’s disease before making this diagnosis
Autosomal dominant trait in Mennonites in Canada
Early childhood diarrhea and dehydration may be fatal
May have common variable immunodeficiency but no malabsorption
Micro: lamina propria edema, shortened and broadened villi, focal acute inflammatory changes
Backwash ileitis and involvement of appendix occurs in continuity with severe colitis; also postcolectomy pouchitis
Rarely diffuse duodenitis is associated with ulcerative colitis, but it does not behave as Crohn’s disease, AJSP 2000;24:1407
Infectious disorders
Usual intestinal fluid input is 9 liters/day (oral intake-2, saliva-1, gastric-2, pancreatic-2, intestinal-1, other-1); most reabsorbed in small bowel and colon
Diarrhea: increase in stool mass, frequency or stool fluidity
Dysentery: low volume, painful, bloody diarrhea
Secretory diarrhea: >500 ml of fluid stool per day, isotonic with plasma, persists during fasting
Infectious (viral damage to epithelium): rotavirus, Norwalk virus, enteric adenoviruses, calicivirus, astrovirus
Infectious (enterotoxin): Vibrio cholera, E. coli, Bacillus cereus, Clostridium perfringens
Neoplastic: tumor production of peptides, villous adenoma in distal colon
Excessive laxatives
Osmotic diarrhea: due to luminal solutes, abates with fasting, stool osmolality > electrolyte concentration by 50 mOsm; associated with lactase deficiency, lactulose therapy, gut lavage, antacids, primary bile acid malabsorption
Exudative disease: purulent bloody stools, persists with fasting: due to bacteria (Salmonella, Shigella, Campylobacter), Entamoeba histolytica, idiopathic inflammatory bowel disease, typhlitis
Malabsorption: bulky stools, abates with fasting, due to defective intraluminal digestion, primary mucosal cell abnormalities, reduced small bowel surface area, lymphatic obstruction, Giardia lamblia
Deranged motility: improper gut neuromuscular function causes decreased transit time; due to surgical resection of gut, irritable bowel syndrome (neural dysfunction), hyperthyroidism, diabetic neuropathy, carcinoid syndrome; decreased motility due to small bowel diverticula, blind loop, bacterial overgrowth
Epidemiology: 12,000 deaths/year from dehydration in developing countries; 50% of all deaths before age 5; affects 40% of US population - #2 in attack rates in US after common cold
Micro: patchy lesions with variable villus abnormality, rarely severe; increased chronic and acute inflammatory infiltrate in epithelium and lamina propria
Due to ingestion of pre-formed toxin (Staphylococcus aureus, Vibrio cholera, Clostridium perfringens), infection by toxigenic organisms or infection by enteroinvasive organisms which invade and destroy mucosal epithelium cells
Bacterial adhere to mucosal epithelial cells, elaborate enterotoxins, have capacity to invade
Adherence by plasmid-mediated adhesins in E. coli and V. cholera; may be via fimbriae or pili; adhesion destroys microvilli brush border
Enterotoxins: bind to cell membrane, enter cell, activates massive electrolyte secretion (cholera toxin, E. coli heat-labile and heat-stable toxins produce travelers diarrhea); no white blood cells in stool
Cytotoxins: Shiga toxin, enterohemorrhagic E. coli
Bacterial invasion: enteroinvasive E coli and Shigella have plasmid that mediates epithelial cell invasion via microbe-simulated endocytosis; then intracellular proliferation, cell lysis, cell to cell spread
Salmonella: invades via transcytosis with minimal epithelial damage
Yersinia enterocolitica: penetrates ileal mucosa, multiplies in Peyer’s patches and regional lymph nodes
Patients ingest preformed toxins: symptoms within hours; explosive diarrhea and acute abdominal distress; 1-2 days
C. botulinum may produce rapid, fatal respiratory failure
Infection with enteric pathogens: incubation of hours-days; diarrhea and dehydration (secretory enterotoxin) or dysentery (cytotoxin or enteroinvasive)
Travelers diarrhea: fecally contaminated water/food; begins abruptly, subsides in 2-3 days
Insidious infection: Yersinia and Mycobacterium tuberculosis
Complications due to massive fluid loss and loss of mucosal barrier include dehydration, sepsis, perforation
Micro: decreased epithelial cell maturation, increased mitotic figures, hyperemia and edema of lamina propria, variable neutrophils, modest villus blunting of small bowel; late - lymphocytes, plasma cells, regenerative change
DD: inflammatory bowel disease
AIDS / HIV
Associated with Kaposi’s sarcoma, lymphoma, smooth muscle tumors; also infectious disorders (see below)
30-60% with HIV infection historically had diarrhea and either malabsorptive symptoms with villus atrophy or colitis resembling ulcerative colitis
Must rule out presence of other infectious organisms
Case report of patient with abdominal pain and peripheral eosinophilia after eating raw salmon from Pacific Ocean, AJSP 2003;27:1167
Micro: serositis, mucosal edema, submucosal abscess with eosinophils surrounding parasite with unpaired excretory gland (renette cell), Y-shaped lateral epidermal cords, no apparent reproductive system, and a ventriculus (glandular esophagus); no lateral alae, no ventricular appendage, no intestinal cecum
Campylobacter jejuni and others invade small bowel or colon
Bacteria found in milk or poultry or transmitted from animal contact
Causes dysentery or diarrhea
Micro: villus blunting, purulent exudate
Infection by nematode Capillaria philippinensis; described in Philippines, Thailand, Iran, Korea, Egypt
May cause protein-losing enteropathy
Worms infest jejunum and upper ileum; resemble trichuriasis
Diagnosis: worms, eggs, larvae in stool
Clostridium difficile
Produces cytotoxin; locally invasive only
Nosocomial environmental spread
Produces bloody diarrhea after antibiotics (antibiotic associated colitis)
Clostridium perfringens
Produces enterotoxin; usually noninvasive
Transmitted from meat, poultry, fish
Causes watery diarrhea
Clostridium perfringens, type C strain
Produces severe necrotizing enterocolitis of jejunum and ileum (enteritis necroticans) with perforation, also called pigbel, a pidgin English term for abdominal pain after a pig feast, reflecting a 1963 cluster of cases
Usually associated with severe protein malnutrition in parts of Asia, Africa, South Pacific
Rarely occurs in developed countries in patients with diabetes
Case report of 66 year old black woman with Type 2 diabetes mellitus who developed severe abdominal pain and bloody diarrhea after eating cooked turkey sausage prepared in Illinois, Mod Path 2002;15:66
Occurred after World War II in previously starved children/adults after eating large meals of meat and vegetables
High mortality rate unless diagnose early and treat with antibiotics or surgical excision of necrotic bowel; preventative vaccine is available for toxin
Gross: segmental necrosis of proximal jejunum
Gross/micro images: image1
CMV duodenitis may present with bleeding or ulceration
Associated with immunosuppression, HIV; usually reflects disseminated infection if present in gut
May cause necrotizing injury and perforation
Micro: inclusions in endothelial cells, fibroblasts, smooth muscle cells
Cryptosporidium parvum
Associated with immunosuppression, HIV; rarely with contaminated water
Self-limited disease in immunocompetent; in immunocompromised, causes severe, watery diarrhea resistant to most therapy
Diagnosis: acid-fast infective oocyst in stool
Micro: 2-5 micron basophilic spherical structures attached to microvillus surface of epithelium; variable villus abnormality, may have eosinophils infiltrating mucosa
Micro images: image1, image2, image3
Positive stains: Giemsa, silver stains, PAS
DD: mucin, cellular debris
Diagnosis: oocyst in stool with modified acid-fast stain
Micro: resembles isospora
EM: helpful for diagnosis
Dysentery causing protozoa
Increased incidence in homosexual men and AIDS patients; can cause fulminant colitis
Fecal-oral spread
Amoeba invade colonic crypts, burrow into lamina propria, create flask shaped ulcer with broad base
40% invade portal vessels, embolize to liver and cause abscesses up to 10 cm
Rare abscesses in lung, heart, kidneys, brain
Causes traveler’s diarrhea (watery diarrhea, hemorrhagic colitis / hemolytic-uremic syndrome)
Different types of E. coli infection:
Enterotoxigenic: cholera like, not invasive, from food, water
Enterohemorrhagic: Shiga-like toxin, not invasive, from undercooked beef
Enteropathogenic: enterocyte effacement, no invasion, from weaning foods, water
Enteroinvasive: invasion and local spread, from cheese, water, person-to-person spread
Associated with malabsorption, chronic diarrhea
Spread by fecally contaminated water, common in underdeveloped countries
Affects 1/3 of homosexual men in urban communities
Attaches to mucosa but does not invade
Diagnosis: detect cysts, trophozoites or antigens in stool
Micro: variable villous blunting, increased inflammatory cells, organisms are teardrop (pear) shaped with paired nuclei in lumen between villi; size of organism is similar to enterocyte nuclei
Micro images: H&E, stool exam
Positive stains: trichrome with iron hematoxylin counterstain, Giemsa stain
Ovoid developmental forms in and beneath epithelial cells near villus tip
Causes chronic diarrhea and acalculous cholecystitis in AIDS patients
Diagnosis: cysts in stool, biopsy (H&E or EM)
Micro: cysts present in parasitophorous vacuole in lamina propria
Positive stains: Giemsa
References: Hum Path 2001;32:500
Intracellular protozoa that infects macrophages and may disseminate throughout reticuloendothelial system
Case report of visceral leishmaniasis and mycobacterial infection in same lesion in AIDS patient, Archives 1999;123:835
Micro images: image1
EM images: image1
Associated with immunosuppression, HIV
Caused by Enterocytozoon bieneusi, an obligate intracellular protozoan that affects only enterocytes and Encephalitozoon intestinalis, which infects macrophages, fibroblasts, endothelial cells, enterocytes; both cause chronic diarrhea in AIDS patients
Diagnosis: stool examination, PCR
Treatment: albendozole for E. intestinalis, nothing for E. bieneusi
Micro: minimal/no changes in mucosa but can find development spores as 1.5 mm dots in enterocytes; may be surrounded by halos; also nucleated sporont present as 3-5 micron, rounded, basophilic structure often surrounded by a halo
Positive stains: Giemsa
EM: often helpful for diagnosis
Atypical mycobacteria
May resemble Whipple’s disease; associated with immunosuppression, HIV
Usually part of disseminated infection
Micro: foamy macrophages fill lamina propria; usually patchy, no fat vacuoles
Positive stains: PAS (faintly positive bacillary forms), acid-fast stains
DD: Whipple’s disease
Mycobacteria tuberculosis
Common in some parts of world
Invasive bacteria transmitted via contaminated milk
Symptoms: abdominal pain, malabsorption, strictures, perforation, fistula
Sites: terminal ileum, cecum, appendix
Gross: multiple and circumferential ulcers and strictures
Micro: confluent granulomas with central necrosis and peripheral lymphocytosis; destruction of muscularis propria, scarring
Positive stains: acid-fast stains
DD: Crohn’s disease (linear and serpiginous ulcers)
Symptoms vary from food poisoning to typhoid fever (S. typhi)
Typhoid fever: bacteremia, fever, systemic dissemination, chronic infection of joints, biliary tree, bones, meninges
From contaminated milk, eggs, beef, poultry
Usually affects terminal ileum
Micro: ulcers overlying Peyer’s patches with minimal inflammatory cells; often histiocytes with erythrophagocytosis
Strongyloides stercoralis
Nematode whose larvae buries into mucosa of duodenum and jejunum, where they mature into adults; females then lay eggs, which develop into larvae that pass into the stool, where they mature and become infective
Infective larvae penetrate intact skin, usually through feet; larvae enter circulatory system, are transported to the lungs, enter the alveolar spaces, are carried to trachea and pharynx, are swallowed, and enter the intestinal tract, where the process is repeated
If larvae become infective before leaving the body, they may invade the intestinal mucosa or perianal skin, causing autoinfection (see life cycle)
Symptoms: none, diarrhea, malabsorption; severe/fatal infections in immunocompromised, due to worms moving from GI tract into other organs (WormBook 2007 May 23:1).
Diagnosis: larvae in stool; adult female or eggs in small bowel mucosa, often with eosinophilic or granulomatous inflammation
Case reports: Case of the Week #133
Treatment: antihelminths such as thiabendazole (Ann Pharmacother 2007;41:1992); prevention is by wearing shoes in endemic areas
Micro images: case of the week - #1; #2; #3
Micro virtual slide: image1
Noninvasive bacteria, produces enterotoxin
Transmitted via water, shellfish, person-to-person; spreads via pandemics
Produces water diarrhea, cholera
Also called intestinal lipodystrophy
Rare systemic condition, usually affects proximal intestine, mesenteric lymph nodes
Caused by Tropheryma whippelii, a gram positive intracellular actinomycete
Affects whites, age 30-49, 90% males
Symptoms: malabsorption with diarrhea, weight loss, abdominal pain; occasionally polyarthritis, CNS complaints, lymphadenopathy, hyperpigmentation; cardiac involvement less common
Fatal without antibiotics
Diagnosis: PCR, immunohistochemistry, PAS stain
Treatment: antibiotics; relapses are common
Gross: shaggy mucosa, edematous bowel wall
Micro: distended macrophages in lamina propria containing PAS+ granules and rod shaped bacilli by EM; dilated lymphatics or fat vacuoles; no other inflammatory cells
In mesentery or retroperitoneal nodes, resembles lipogranulomatous inflammation with round empty spaces
Note: after treatment, macrophages decrease in lamina propria but remain present elsewhere for years; cytoplasmic inclusions become tissue-paper like with PAS, resembling Gaucher’s cells
Micro images: contributed by Drs. Derek Mathis and Rosemarie Rodriguez, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas (USA) - #1; #2; #3; #4; #5; #6; #7; PASD#1; PASD#2; PASD#3; PASD#4; PASD#5
Positive stains: PAS, anti-T whippelii immunostain
EM: rod-shaped bacteria
DD: mineral oil ingestion, mycobacterium avium-intracellulare infection (in immunocompromised, patchy, no lipid vacuoles, PAS shows faintly positive bacillary forms), histoplasmosis (faint blue dot-like inclusions surrounded by a clear halo, PAS or silver stain shows budding yeast)
References: Hum Path 2003;34:589
Common cause of bacterial enteritis in US, Canada, Australia, Western Europe, Northern Europe
Infection due to Y. enterocolitica or Y. pseudotuberculosis, gram negative invasive rods
Due to infected milk, pork, water supplies, domestic pets and farm animals
Causes enterocolitis, acute appendicitis, mesenteric lymphadenitis in children and adolescents
Pathogenic strains invade small intestinal mucosa via M cells overlying Peyer’s patches, multiply there and within regional nodes, then spreads hematogenously and via lymphatics
Patients homozygous for thalassemia major are at risk of Y. enterocolitica as they have iron overload and the bacteria requires iron for growth
Sites: ileum, right colon, appendix
Case report of intussusception due to Y. enterocolitica infection in beta-thalassemia patient, Archives 2001;125:1486
Diagnosis: culture
Micro: elongated ulcerations overlying lymphoid hyperplasia; also small aphthoid ulcers overlying colonies of gram negative rods and with neutrophils at ulcer base; also necrotizing granulomas (particularly with Y. pseudotuberculosis)
Micro images: image1
DD: typhoid fever
Obstruction
Due to mechanical factors (adhesions, hernias, volvulus, intussusception, tumors, inflammatory or congenital strictures, gallstones, fecaliths, foreign bodies, atresia, bands, mesenteric ossification, AJSP 1999;23:1464), disturbances in peristalsis (postoperative paralytic ileus, myopathy, Hirschsprung’s)
80% due to hernias, intestinal adhesions, intussusception, volvulus
May cause stasis, with resulting malabsorption
Symptoms: pain, distension, vomiting, failure to pass flatus
Children: usually congenital
Adults: idiopathic or due to diabetes, scleroderma or other systemic disease
Treatment: dietary changes, medication (octreotide), surgery, intestinal transplantation
Micro: patchy mucosal changes of variable villus abnormality, increased chronic inflammatory cells in epithelium and lamina propria, occasional neutrophils
Causes: post-operative, infections, endometriosis
Adhesions are between bowel segments or abdominal wall and operative site
May create internal herniations (closed loops through which viscera slide)
Rarely adhesions are congenital
Gross images: image1
Chronic idiopathic intestinal pseudo-obstruction
Symptoms of intestinal obstruction without mechanical obstruction
Attributed to abnormal physiology of gut propulsive system; due in some cases to marked reduction in interstitial cells of Cajal, AJSP 2003;27:228
Causes: local manifestation of generalized disease (diabetes, hypoparathyroidism, pheochromocytoma, Parkinson’s disease, SLE, drug effect [mushroom poisoning, antiparkinsonian drugs, clonidine], psychosis, diseases with intestinal pathology [myxedema, dermatomyositis/polymyositis, amyloidosis, Chagas’ disease, myotonic dystrophy, Duchene’s muscular dystrophy, scleroderma]
By definition, excludes known causes of obstruction: ceroidosis, cathartic colon, Hirschsprung’s disease, visceral myopathies (muscle cell degeneration/loss, fibrosis of muscularis propria), visceral neuropathies (familiar, sporadic; require special techniques to demonstrate)
Protrusion of pouchlike, serosa-lined sac of peritoneum (hernia sac) through weakness or defect in wall of peritoneal cavity
Usually inguinal and femoral canals, umbilicus and surgical scars; rarely around ligament of Trietz
Viscera may protrude and become trapped in hernias, including bowel loops and omentum
Complications: incarceration, strangulation, infarction
Also called progressive systemic sclerosis
Patchy bowel involvement
Dense fibrosis replacing entire muscularis propria or accentuated in inner layer
No vacuolar change
Complete twisting of a loop of bowel about its mesenteric base of attachment
Produces intestinal obstruction and infarction
Usually in redundant loops of bowel
Gross images: image
Other / benign tumors and tumor-like conditions
Rare compared to colon
Often present in patients with familial adenomatous polyposis or Gardner’s syndrome
Single or multiple, sessile or pedunculated, tubular or villous or mixed
May become malignant, particularly if large, villous, multiple
Diagnose with rectal biopsy that includes submucosa
Primary: GI involvement in 70% of cases, amyloid in blood vessel walls and muscularis propria
Secondary: GI involvement in 50% of cases, often deposits in blood vessel walls in lamina propria
May occur after barium enema if barium penetrates mucosal tear and stimulates a granulomatous reaction
Crystals visible under polarized light
Rarely produces polypoid or ulcerated lesion resembling a neoplasm
Micro: barium is green and crystalline; crystals within clusters in macrophages or connective tissue
Blue rubber bleb nevus syndrome
Autosomal dominant or sporadic
Skin or visceral hemangiomas
Brown bowel syndrome
Also called ceroidosis
Prominent dark brown or orange-brown discoloration of bowel wall on serosa and cut surfaces
Due to lipofuscin, associated with malabsorption (? vitamin E deficiency)
Micro: prominent lipofuscin granules in smooth muscle cells
DD: melanosis coli (in mucosa)
Rare benign lesion of duodenum
Case report in 43 year old man, Archives 2002;126:734
Gross: pedunculated tumor of submucosa
Micro: adipose tissue, hyperplastic Brunner’s glands, cystic ducts lined by ciliated cells
Micro images: image1
Also called Brunner’s gland hyperplasia or adenoma
Nodular proliferation of normal Brunner’s glands, ducts, stroma; usually in mid duodenum
Associated with erosions and duodenitis; may cause melena or obstruction
Probably not neoplastic
Clofazimine is used to treat leprosy and Mycobacterium avium complex in HIV patients
May cause severe abdominal pain; also red skin discoloration and ichthyosis
Micro: red crystals in frozen section with bright-red birefringence; clear in routinely processed histologic sections; causes histiocytosis resembling lymphoma, plasmacytosis
EM: clear spaces with some osmiophilic bodies
References: AJSP 2000;24:129
Micro: abundant epithelial mitotic figures with metaphase arrest; often enlarged epithelial cells with condensed chromatin in a ring formation within center of cell; associated with epithelial loss of polarity and pseudostratification; nuclei small, hyperchromatic and compressed to periphery of cell
References: AJSP 2001;25:1067
Common variable immunodeficiency syndrome
Chronic diarrhea, malabsorption, recurrent GI giardiasis
Mucosa may resemble celiac sprue or be normal, but always has reduced plasma cells and no IgA plasma cells; may have lymphoid hyperplasia or apoptotic bodies in crypts
Cowden's syndrome
Also called multiple hamartoma syndrome
Autosomal dominant with facial tricholemmomas, acral keratosis, oral mucosal papillomas, small intestinal and colorectal polyps
Increased risk of malignancy (breast and thyroid cancer), but not in polyps
Polyps have same histology as mucosal prolapse syndromes (colitis cystica profunda)
Micro: hamartomatous features with disorganization and proliferation of muscularis mucosa
DD: Peutz-Jeghers
Non-hereditary disorder of multiple juvenile type polyps, usually colonic, associated with ectodermal changes (alopecia, nail atrophy, hyperpigmentation)
80% present at age 50 or older
Symptoms: diarrhea, weight loss, abdominal pain, weakness, anorexia; 50% die of cachexia
Polyps present in stomach or colorectum; less pedunculated than other juvenile polyps
May develop adenomas, adenocarcinoma
Micro: juvenile-type polyps, with cystically dilated glands in polyp and nonpolypoid mucosa; no dysplasia
Mean age 44 years, range 28 to 56 years
May cause obstruction or mimic other diseases
Presents with pain, mass or incidental findings
Rarely complicated by neoplasms or precancerous changes, AJSP 2000;24:513
Endometriosis associated tumors include endometrioid carcinoma, MMT, Hum Path 2000;31:456
Gross: serosal and subserosal nodules < 5 cm; smooth muscle hypertrophy; gray cut surface with minute areas of hemorrhage
Micro: endometrial glands, stroma, hemosiderin in deeper layers; epithelium may have inflammation and ulcers, simulating inflammatory bowel disease or solitary rectal ulcer syndrome; fibrosis of bowel wall, neuronal hypertrophy; mucosa usually normal
Micro images: image1
Positive stains: CD10 (endometrial stroma)
References: AJSP 2001;25:445
Mucosal glands and mucinous cysts in submucosa or deeper
Also called intraabdominal desmoid tumor
Uncommon, usually in mesentery or retroperitoneum; rarely adheres to or penetrates bowel wall
Mean age 34 years old (younger than GIST patients)
May be associated with trauma, familial polyposis coli, Gardner’s syndrome, hormonal stimulation
Benign, but may recur
Treatment: surgical excision, radiation therapy, possibly chemotherapy
Gross: firm, tan, homogenous; usually large (6 to 25 cm) and infiltrative margins
Micro: broad, sweeping fascicles of bland spindle cells with minimal overall mitotic activity (mean 4 mitoses/50 HPF), bland nuclear features, finely collagenous stroma; infiltrative borders, evenly spaced blood vessels; may involve muscularis propria but no necrosis, no hemorrhage, no myxoid degeneration, no epithelioid cells, no pleomorphism, no foam cells, no inflammatory cells
Positive stains: vimentin, smooth muscle actin, desmin (50%)
Negative stains: CD34, S100, CD117 (some antibodies give CD117+ results)
EM: myofibroblastic/fibroblastic differentiation
DD: GIST (CD117+ with all antibodies, often CD34+, often malignant histologic features)
References: AJSP 2000;24:947, Mod Path 2003;16:366
Rare tumor of periampullary region and second portion (middle) of duodenum; rarely in jejunum or ileum
May be multiple or associated with neurofibromatosis 1 or carcinoid syndrome
Usually benign, rarely has metastases of endocrine component
Case report of metastatic tumor in regional lymph nodes containing spindle cell, epithelial and ganglion components, Archives 2003;127:e139
May derive from endodermal-neuroectodermal complexes in the embryonic ventral pancreas, due to totipotential nature of adult stem cells that differentiate along different lineages
Gross: usually 1-3 cm, sessile or polypoid
Gross images: malignant tumor
Micro: submucosal lesion(s) with overlying ulcerations; organoid pattern; triphasic with endocrine (carcinoid like cells in compact nests and trabeculae), spindle cell (Schwann cell like), and ganglion type cells of varying proportions resembling carcinoid, paraganglioma and ganglioneuroma; variable stromal amyloid
Micro images: malignant tumor
Positive stains: pancreatic polypeptide (in endocrine cells, not specific to this tumor), keratin (epithelial cells), S100 (spindle cells), neuron specific enolase (ganglion cells)
DD: ganglioneuroma, paraganglioma, carcinoid, carcinoma
Multiple tumors associated with neurofibromatosis type 1, MEN 2b/3 or sporadic (rare, usually solitary)
Usually arise from nerves within bowel wall, may be mucosal
Gross: polypoid
Micro: proliferation of ganglion cells and Schwann cells in mucosa and deeper layers; may see accentuation of submucosal and myenteric plexus in MEN 2b/3
Positive stains: S100, NSE
Single or multiple, often in mid-jejunum
Rare, may cause obstruction, intussusception, melena or anemia
Diffuse lesions, circumscribed tumors or papillary growths
May be associated with hemangiomas elsewhere
Capillary: usually asymptomatic, small, solitary, composed of closed packed capillaries
Cavernous: localized or diffuse; blood filled sinuses with minimal connective tissue; symptoms of a mass or bleeding
Arteriovenous: abnormal veins and arteries; otherwise resembles cavernous hemangioma
Complications: perforation, hemorrhage
Hemorrhagic necrosis of GI tract
Also called typhlitis, neutropenic or necrotizing enterocolitis, ileocecal syndrome
Affects terminal ileum, cecum, right colon
Associated with immunosuppression, leukemia, lymphoma
Prominent overgrowth of bacteria and fungi and minimal active inflammation
Hereditary hemorrhagic telangiectasia
Autosomal dominant syndrome of multiple vascular lesions of mucous membrane, skin and internal organs
Associated with severe GI hemorrhage
Difficult to identify at time of surgical resection
Hyperplastic Pacinian corpuscle
Intraabdominal Pacinian corpuscles up to 1 cm
Micro: resembles cutaneous counterpart; central blood vessel and nerve ending surrounded by 14-45 tortuous, concentric lamellae
DD: nematode (has cuticle, internal structures)
Idiopathic retractile mesenteritis
Also called mesenteric panniculitis
Rare, idiopathic, nonneoplastic condition usually affecting small bowel, which can cause thickening and shortening of mesentery
Usually men age 40+, associated with signs/symptoms of intestinal obstruction but no other systemic symptoms
Micro: fibrosis, fat necrosis, chronic inflammation, variable focal calcification; minimal atypia or mitotic figures
Idiopathic retroperitoneal fibrosis
Fibrosis develops in retroperitoneum, often at aortic bifurcation
Associated with drug methylsergine, other fibrotic lesions (sclerosis of major bile ducts, Riedel’s thyroiditis, inflammatory pseudotumor of orbit)
Associated with lymphoma, which developed in 15% of patients
Gross: not well circumscribed
Micro: widely scattered germinal centers and plasma cells in background of dense fibrosis
Benign, usually in distal stomach or terminal ileum
Presents as obstructive mass or causing intussusception (Radiographics 1999;19:539).
Case reports: Case of the Week #86, in a Crohn’s patient (Ann Ital Chir 2005;76:395)
Treatment: excision (does not recur)
Gross: polypoid, submucosal mass
Micro: submucosal mixture of prominent capillaries, spindle cells and inflammatory cells (particularly eosinophils) in granulation tissue-like stroma; may be transmural; no atypia, no/rare mitotic figures
Micro images: image #1; #2; #3; #4; #5; #6; #7
Positive stains: CD34; variable smooth muscle actin
Negative stains: CD117 (although mast cells are positive)
DD: inflammatory myofibroblastic tumor (usually children, may recur, plasma cells and lymphocytes with few eosinophils, mitotic activity in cellular areas, less prominent blood vessels, smooth muscle actin+, desmin+, ALK+/-, CD34-, Hum Path 2002;33:307), GIST (malignant in 30-50%, plump spindle cells with eosinophilic cytoplasm, variable skenoid fibers and muscular infiltration, CD117+), inflammatory polyp of Crohn’s or ulcerative colitis (similar histology but different clinical history and findings in remainder of bowel)
References: Mod Path 2000;13:1134-free full text, Mod Path 2003;16:366-free full text).
Inflammatory myofibroblastic tumor
Also called inflammatory pseudotumor, inflammatory fibrosarcoma
Often in children but can occur at any age, no clinical associations
Benign, but may recur; rarely behaves malignant
22% of tumors (all sites) are positive for anaplastic lymphoma kinase (ALK) in patients 40 years or younger; these patients have a more favorable prognosis, AJSP 2001;25:761
Complications: obstruction, intussusception
Gross: mean 3-4 cm, submucosal sessile polypoid mass or multiple masses with broad base; tan/gray/yellow; overlying mucosa may be ulcerated
Micro: usually limited to submucosa; spindle cell lesions with inflammatory infiltrate including plasma cells and lymphocytes; may be sparsely cellular with myxoid stroma; cellular areas may have up to 2 mitotic figures/HPF; variable vascular component; may have rarefaction around muscular-walled blood vessels, may be infiltrative
Micro images: image1
Positive stains: vimentin, muscle specific actin, smooth muscle actin, anaplastic
lymphoma kinase (variable)
Negative stains: S100, desmin (Mod
Path 2000;13:1134), CD117
(endothelial cells may be CD117+), CD34
EM: myofibroblasts
DD: fibromatosis (invades bowel secondarily)
Associated with Crohn’s disease or ulcerative colitis; also amebiasis, schistosomiasis, ulcers, anastomotic sites
Micro: solitary small polyps of inflamed regenerating mucosa in a fibroblastic or granulation tissue stroma; no/few mitotic figures, no atypical mitotic figures, often zonation; may have bizarre stromal changes resembling sarcoma
Portion of bowel (intussuscipiens) swallows another length of bowel (intussusceptum)
Usually during first 5 years of life, 50% within first year
May to due to lymphoid hyperplasia in ileocecal region secondary to adenovirus or other viral infections
In older patients, may be associated with HIV or due to pedunculated intraluminal lipoma or leiomyoma that serves as point of traction
Complications: ischemic necrosis due to compression of vessels
Treatment: manual reduction, barium enema, resection
Due to vascular occlusion or reduced blood flow associated with shunting; usually not due to atherosclerosis due to widely anastomosing blood supply
Damage varies from none to hemorrhagic infarction; also ulceration, mucosal plaque, strictures
Grossing bowel specimens with possible ischemia: dissect blood vessels and submit several sections to detect inflammation and thrombosis
Gross images: infarction, early ischemia, hyperemia
Micro - early: lamina propria hemorrhage, superficial epithelial necrosis, preservation of deep crypts
Later: ulceration with minimal inflammation, villous distortion, pyloric gland metaplasia progressing to full thickness infarct
Late: strictures affecting muscularis propria
DD: Crohn’s disease (marked inflammatory infiltrate, no stricture of muscularis propria, no hemosiderin)
Kayexelate (sodium polystyrene sulfonate) in sorbitol is used to treat hyperkalemia, may crystallize in small intestine (also elsewhere in GI tract) and produce endoscopic findings resembling 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
Klippel-Trenaunay-Weber syndrome
Hemangiomas, somatic and bony hypertrophy, port wine stains, urinary bladder hemangiomas
Arise from muscularis propria or muscular mucosa
Leiomyoma of muscular mucosa of duodenum are incidental, 1-2 mm, merge with muscularis mucosa
Gross (not from muscularis mucosa): 2-4 cm, often incidental finding, firm, white, whorled cut surface
Micro: low cellularity, no/rare mitotic figures, resembles esophageal leiomyoma
Positive stains: smooth muscle actin, desmin
Negative stains: CD117, CD34
References: AJSP 2003;27:625
Rare, usually submucosal
May cause ulceration or intussusception
Lipohyperplasia often found near ileocecal valve
Gross: bright yellow, round, encapsulated; bulges into lumen, 5% multiple; may have hemorrhage or necrosis
DD: lipomatosis (bowel infiltrated by mature fat)
Dilation of lymphatics in mucosa, submucosa or subserosa; diffuse or focal; no other abnormalities
Associated with protein-losing enteropathy, hypoalbuminemia, edema, lymphocytopenia
Primary: children, due to congenital obstructive defective in lymphatics
Secondary: due to retroperitoneal fibrosis, pancreatitis, constrictive pericarditis, myocardial disease, intestinal malignancy, Waldenström macroglobulinemia, sarcoidosis
Treatment: resection, treatment of underlying conditions
Usually children, associated with similar tumors elsewhere
DD: lymphatic cysts (incidental finding in elderly)
Also called lymphoid polyp; formerly called pseudolymphoma
Most common site is ileocecal region
Causes intussusception in children
Nodular lymphoid hyperplasia: nodules throughout bowel, associated with giardiasis or childhood viral infection
Note: bcl2 is expressed in marginal zone cells in hyperplastic areas, but this should not be confused with follicular lymphoma, AJSP 2003;27:888
DD: low grade lymphoma
Rare systemic disorder with mast cells in skin, bones, lymph nodes, other organs; 50% involve GI tract and may cause malabsorption; rarely involves small bowel without skin involvement
Consider if 6 or more mast cells present per high power field
Micro: variable villus abnormality with increased mast cells or eosinophils
Extremely rare
May be part of Carney complex (familial myxoma syndrome), an autosomal dominant syndrome with a mutation at 17q2 of cardiac and cutaneous myxomas, lentigines, myxoid fibromas of the breast, pituitary adenomas, primary adrenocortical micronodular hyperplasia with Cushing syndrome, testicular large cell calcifying Sertoli cell tumor, psammomatous melanotic schwannoma
Case report of simultaneous cardiac and small bowel myxoma in 47 year old woman, Archives 2003;127:481
Gross/micro images: image1
Gross: intraluminal, pedunculated, firm round nodule with smooth and ulcerated mucosal surface, myxoid and gelatinous cut surface
Micro: bland, stellate stromal cells and small, mature capillaries widely separated by myxoid material; scattered lymphocytes and plasma cells; no mitotic activity, no atypia
Positive stains: vimentin
Negative stains: CD117/c-kit, CD31, smooth muscle actin, S100
Associated with multiple endocrine adenomatosis or von Recklinghausen’s disease (neurofibromatosis 1)
With NF1, also associated with hyperplasia of submucosal and myenteric nerve plexuses, mucosal ganglioneuromatosis, GI stromal tumors, gangliocytic paraganglioma
Neuromuscular and vascular hamartoma of small bowel
Also called hamartoma
Similar to diaphragm disease (annular constrictions causing small bowel obstruction, although associated with NSAIDs)
Gross: multiple circumferential indentions of serosa corresponding to discrete ridges on mucosal surface
Micro: ridges composed of submucosa only, contain proliferating blood vessels surrounded by smooth muscle fibers originating from a frayed muscularis mucosa; variable nerve and ganglionic cells present in fibrous collagenous tissue; no/minimal inflammatory infiltrate
References: AJSP 2001;25:539
Also called hamartomatous polyp
Prevalence of 1 per 200,000
Peutz-Jeghers syndrome: autosomal dominant disorder with variable penetrance, usually diagnosed in 20’s; hamartomatous polyps in stomach and colon (25%), small bowel (100%); melanotic pigmentation of lips, oral mucosa, digits, palms, soles, genitalia; adenocarcinoma of stomach, large or small bowel, sex-cord tumor with annular tubules (almost all), adenoma malignum of cervix, ovarian mucinous tumors, carcinomas of breast, uterus, pancreas, lung
Polyps may occur without other features of syndrome, may be associated with enteritis cystica profunda, may cause intussusception and bleeding
Polyps are benign, but adenocarcinoma may arise from associated adenomatous lesions
Large polyps may cause intussusception and GI bleeding
Misplaced dysplastic epithelium may resemble malignancy, AJSP 2000;24:34
Gross: adenomatous-like polyps; pedunculated, large, lobulated
Micro: polyp supported by broad bands of muscularis mucosa smooth muscle, thicker centrally; “Christmas tree” appearance at low power; columnar and goblet cells superficially; Paneth and endocrine cells at base; epithelial misplacement (pseudoinvasion) in 10%
Micro virtual slide: image1
DD: invasive carcinoma, enteritis cystica profunda
Pneumatosis cystoides intestinalis
Submucosal gas-filled cysts in GI tract; if resembles lipomatosis, called mucosal pseudolipomatosis
In infants, associated with necrotizing enterocolitis and may be fatal; also associated with cystic fibrosis or congenital heart defects
In adults, either idiopathic or associated with obstruction, chronic lung disease, scleroderma, chemotherapy, drugs, ischemic colitis
Often indolent clinical course, although radiographically resembles carcinoma
Consider a finding, not a diagnosis
Gross: polypoid grapelike masses protrude through mucosa
Micro: submucosal cysts lined by multinucleated giant cells; mucosa contains cryptitis, crypt abscesses, granulomas; may also resemble lipomatosis
Gross/micro images: image1
DD: Crohn’s disease
References: Archives 1999;123:354
Brown-black pigment in lamina propria macrophages of proximal duodenum, due to iron and sulfur, not lipofuscin
No known clinical significance
Pigment may originate in atmosphere or diet
Observed years after radiation therapy for cervical carcinoma, Wilm’s tumor, lymphoma or other peritoneal tumors
Treatment: resection if severe
Gross: thickened bowel wall
Micro: early-nuclear atypia of epithelium, fibroblasts and endothelium with submucosal edema but low nuclear to cytoplasmic ratio, preservation of architecture, lack of mitotic figures, no desmoplasia, no infiltrative pattern; late-fibrosis of submucosa and muscular wall, mucosal ulceration and atrophy, possible fistula formation, atherosclerosis-like changes of vasculature (subintimal lipid-laden macrophages, calcification, thrombosis), hyalinization of lamina propria
Reactive nodular fibrous pseudotumor
First described in 2003 in 5 patients (4 men), mean age 56 years, AJSP 2003;27:532
Benign clinical course
Gross: firm, tan-white, 4-6 cm, solitary/multiple, in small bowel or colon
Micro: low/moderate cellularity; spindled fibroblasts arranged haphazardly or in intersecting fascicles; often infiltrative borders; stroma rich in wire-like, keloidal or hyalinized collagen; peripheral lymphoid aggregates
Positive stains: vimentin, CD117 or muscle specific actin (80%), smooth muscle actin or desmin (60%)
Negative stains: CD34, S100, alk1
DD: fibromatosis
Inflammatory and fibrosing process affecting visceral peritoneum that can encase small bowel
Infiltrates mesentery at attachment site with peritoneum; usually spares retroperitoneum
Associated with dry eyes and itchy scaly skin lesions
Cause: chronic peritoneal dialysis, beta blockers; also idiopathic
Nodular lymphoid hyperplasia, reduced IgA plasma cells, otherwise normal
Transplantation
Acute changes associated with transplantation (not rejection) are epithelial denudation, crypt regeneration, mild acute inflammation
Acute cellular rejection: weeks-months after transplantation; resembles graft vs. host disease with increase in lymphocytes in lymphoid tissues; crypt epithelial damage and apoptosis, chronic inflammation in lamina propria, epithelial lymphocytosis, lymphocytic infiltration of vessels
Chronic rejection: fibrosis of bowel wall, vascular sclerosis
May develop post-transplantation lymphoproliferative disorders associated with EBV infection
Rejection is monitored by mucosal biopsy
Intractable diarrhea syndrome, sometimes familial, beginning in neonates
Treatment: total parental nutrition
Micro: variable villus abnormality, no epithelial lymphocytosis, epithelial crowding, disorganization and focal tufting
EM: basement membrane abnormalities
XO karyotype with short stature, webbed neck, streak gonads, shield chest
Telangiectasias in bowel
May mimic Crohn’s disease due to mucosal ulceration / gangrene, submucosal edema, perforation and stenosis
Usually due to atherosclerosis; also adhesions, radiation therapy, rheumatoid arthritis, periarteritis nodosa, thromboangiitis obliterans, fungal infection
Intramural phlebitis (enterocolic lymphocytic phlebitis)
May cause ischemic intestinal necrosis
Some cases associated with use of drug hydroxyethyl rutozide; others of unknown origin
Diagnostic criteria: predominantly lymphocytic infiltration of intramural tributaries of mesenteric veins
Case report of 66 year old woman with isolated mesocolic vasculitis, AJSP 2001;25:827
Micro: lymphocytic infiltrate of venules
References: AJSP 2000;24:824, Mod Path 2000;13:897
Carcinoma
2% of malignancies of GI tract occur in small bowel; 5,000 cancers and 1,200 deaths per year in US
Most tumors are adenocarcinomas, often associated with adenomas
Metastases to liver, peritoneal surfaces, regional lymph nodes
Much less common than in colon
Men or women, ages 40-70, any site in small bowel
Duodenal tumors often in ampulla (see Ampulla)
Also associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer), Crohn’s disease, Peutz-Jegher’s syndrome, von Recklinghausen’s disease, cholecystectomy, cystic fibrosis
Make cause obstruction
Usually advanced stage at diagnosis with deep wall penetration, nodal metastases
Mucin staining varies based on site of lesion (see below), Mod Path 2003;16:403
Gross: papillary or polypoid, may have napkin ring appearance (encircles lumen), proximal bowel dilation
Micro: often moderately well differentiation, mucin producing; scattered endocrine cells
Positive stains: mucin, CEA, lysozyme
Duodenum - positive for MUC1, negative for CK20
Jejunum/ileum - negative for MUC1, positive for CK20
EM: prominent microvilli
Rare, case report at Archives 1999;123:739
Micro: malignant glandular and squamous elements
Micro images: image1
Aggressive behavior
Micro: bizarre tumor cells, often multinucleated, with abundant cytoplasm
Usually fatal
Micro: marked pleomorphism, large irregular hyperchromatic nuclei, prominent nucleoli, tumor necrosis, frequent mitotic figures
Micro: marked cytologic atypia, mitotic figures, intracytoplasmic lumina, invasion of lamina propria, extracellular mucin pools
DD: artifacts from trauma, particularly if tissue is fragmented or crushed (Archives 2001;125:1473, figure 2)
Rare, in few cases reported, prognosis better than for small cell lung tumors
Micro: sheets and nests of small, round cells with scanty cytoplasm, hyperchromatic nuclei, stippled chromatin, indistinct nucleoli, numerous mitotic figures and apoptotic cells; foci of necrosis and vascular invasion common; resembles pulmonary tumor; pure or mixed with adenocarcinoma
Gross/micro images: image1 (figure 4 is synaptophysin)
Positive stains: neuroendocrine markers
EM: membrane-bound dense core granules
References: Archives 2003;127:e357
Lymphoma
Among the most common malignant tumors of the small bowel
GI tract is most common site of primary extranodal lymphoma, but also a site of secondary disease in 10% with non-Hodgkin’s lymphoma at presentation
Usually solitary, 50% have nodal metastases at diagnosis
2 year actuarial survival is 42%
If biopsy shows atypical lymphoid proliferation, recommend rebiopsy to obtain fresh tissue for flow cytometry, PCR or gene rearrangement studies
2/3 are B cell, 1/3 are T cell lymphomas
Gross: diffusely infiltrating mass with garden hose appearance OR bulky tumor mass with ulceration OR polypoid growth pattern
Usually children with involvement of ileum and ileocecal value
Sporadic cases in Western world and Middle East may present with ileocecal involvement and pain or obstruction
Endemic cases in Africa usually don’t present with GI involvement
Gross images: contributed by Dr. Kaveh Naemi, Irvine, California - ileocecal valve tumor
Micro: small, noncleaved, monomorphic cells with round nuclei, prominent multiple nucleoli, basophilic cytoplasm; vacuoles on touch prep; starry sky appearance on low power
Micro images: contributed by Dr. Kaveh Naemi, Irvine, California - ileocecal valve tumor - micro #1; #2; #3; #4; CD20; CD10; bcl2; Ki-67
Positive stains: CD20, CD10
Negative stains: CD5, CD23
Molecular: c-myc translocations of t(8;14) and others
Diffuse large B cell lymphoma
Includes cases of MALT and non-MALT origin
Tumors with diffusely dense bcl6 expression may indicate germinal center B cell origin, associated with better survival, AJSP 2003;27:790
Often arises in terminal ileum or as small polypoid masses throughout bowel (lymphomatoid polyposis, which may also represent mantle cell lymphoma)
For primary disease, median age is 54 years; most common site in GI tract is small bowel, often with transmural involvement
Indolent with occasional relapses but no/rare deaths, median disease free survival 69 months, AJSP 2002;26:216
Duodenal cases may be more common in women, are usually periampullary, AJSP 2000;24:688
Gross: bowel thickening with multiple elevated nodules or plaques, possible bowel obstruction
Micro: usually follicular growth pattern of small, cleaved, bland appearing lymphocytes; may transform to higher histologic grade
Positive stains: CD20, CD10, bcl2, CD75, CD79
Negative stains: CD3, CD5, CD23, bcl1/cyclin D1
Molecular: t(14;18)
Resembles sinus histiocytosis with massive lymphadenopathy
Positive stains: CD68
Associated with inflammatory bowel disease or longstanding chronic inflammation, combined with chronic immunosuppression
Stringent criteria suggested due to rarity of primary disease and possible confusion with secondary spread
May be due to Epstein-Barr virus driven proliferation
Case reports in terminal ileum in patients with inflammatory bowel disease, AJSP 2000;24:66, Archives 2001;125:424
Treatment: discontinuation of immunosuppressive therapy may be helpful
Gross: transmural involvement of bowel wall, often multifocal, associated with fissuring ulcers, diverticula with abscesses
Micro: Reed-Sternberg cells in background of lymphoid hyperplasia, occasional granulomas
Micro images: image1
Positive stains: CD15, CD30
Negative stains: CD45 (LCA)
Case report of 57 year old woman with obstructive tumor, Archives 2001;125:677
Often associated with serum viscosity syndrome, often IgM type
Lab: monoclonal serum gammopathy
Micro: nodular or diffuse transmural infiltrate of small lymphocytes, mature plasma cells, lymphoplasmacytoid cells associated with extracellular PAS+ material
Micro images: image1
Tumor of Mucosa Associated Lymphoid Tissue; type of marginal cell lymphoma
More common in stomach than small bowel
Often relapse in GI tract only
Adults, anywhere in gut except rarely in appendix and esophagus
Initially a type of hyperplasia, then monoclonal T cell dependent (from H. pylori infection), then T cell independent
Initial stages may be “cured” by antibiotics or surgery
Micro: low grade - small or monocytoid lymphocytes with irregular nuclei that form lymphoepithelial lesions; reactive germinal centers and plasmacytoid cells are common
high grade - resembles diffuse large B cell lymphoma, but may have Reed-Sternberg like cells
Positive stains: CD20
Negative stains: CD3, CD5, CD10, CD23, bcl1
Molecular: t(11;18) involving c-myc is common
Often presents as multiple lymphomatoid polyposis
Uncommon, 88% males, mean age 61 years
Also involves stomach and colon
Mean survival less than 3 years
Early tumors lack multiple polyposis or multifocal GI involvement; may begin as single lesion or with disseminated multiple mucosal involvement, Mod Path 2001;14:811
Case report of coexistent adenocarcinoma, Archives 2003;127:E64
Gross: nodular, sessile or polypoid lesions, widely spaced with confluent studded or cobblestone appearance; each polyp 2 mm to 2 cm; may be dominant tumor mass in ileocecum
Micro: mantle cells (small lymphocytes with cleaved irregular nuclei), invasion of submucosa, sparing of mucosa; epithelial invasion and ulceration occurs late in disease
Micro images: early tumor #1, #2, early tumor-stains, figures 2/3
Positive stains: CD20, CD5, cyclin D1/bcl1
Negative stains: CD3, CD10, CD23
DD: nodular lymphoid hyperplasia (benign, associated with common variable immunodeficiency syndrome), multiple lymphoid polyps (benign germinal centers in children, patients with Gardner’s syndrome)
Also called immunoproliferative small intestinal disease, Middle Eastern lymphoma
More common among non-European Jews, Middle Eastern Arabs, South African blacks
B cell lymphoma that arises in background of chronic diffuse mucosal plasmacytosis, with IgA heavy chain synthesis (no variable chain synthesized)
Many have pre-existing malabsorption
May initially respond to antibiotics
Gross: low grade - non flattened mucosa; high grade - diffusely thickened folds with small nodules in distal duodenum / proximal jejunum
Micro: low grade - heavy lymphoplasmacytic infiltrate by mature cells; high grade - resembles diffuse large cell lymphoma with plasmacytoid features; may have starry sky pattern, follicular hyperplasia
Positive stains: monoclonal kappa or lambda (not both)
Natural killer cell (NK cell) lymphoma
Case report in patient without gluten sensitive enteropathy, Archives 2003;127:e142
Micro images: image1
Positive stains: CD103, CD7, CD56, CD16, CD3 epsilon
Flow cytometry: image1
Post-transplant lymphoproliferative disorders
May primarily involve the small bowel
Either polymorphic or monomorphic (low grade or high grade)
Case report of HIV patient with small bowel mass, AJSP 2002;26:1363
Also called enteropathy associated T cell lymphoma, ulcerative jejunoileitis
Associated with long standing (mean 28 years) malabsorption that ceases to be gluten-sensitive; 14% incidence in celiac sprue patients
Abdominal pain, fever, intestinal obstruction, perforation, hemorrhage, usually with malabsorption
Ulceration may coincide with or precede detectable lymphoma, but it is difficult to rule out lymphoma (unless have multiple biopsies) since it may be focal
75% dead within 2 years
Symptoms: fever, weight loss, abdominal pain, finger clubbing, bowel ulceration, sustained increase in serum IgA
Gross: widespread patchy involvement, often of small bowel, associated with ulceration, stricture, perforation
Micro: atypical binucleated or multinucleated cells resembling Reed-Sternberg cells in a background of eosinophils and macrophages with erythrophagocytosis, often at base of mucosal ulcers and difficult to identify; severe villus abnormality of flat sprue-like mucosa; may require 20 tissue sections to diagnose malignancy since tumor is so focal
Positive stains: CD3, CD7, CD30
Negative stains: CD4, CD8, CD22, CD68
Rare but distinctive involvement of small bowel
Gross: small white nodules, variable distended serosal lymphatics; mucosa is white, nodular or granular
Micro: marked mucosal and submucosal lymphangiectasia and short, broad villi; coarse eosinophilic material (macroglobulin) in lymphatics, macrophages, lamina propria
Other malignancies
Low grade malignancy arising from epithelial stem cells in crypts
Represents 50% of small bowel tumors
Usually adults in 50’s, also children
Most common in ileum (including Meckel’s diverticulum); also jejunum and distal duodenum
Associated with celiac disease, bowel duplication, von Recklinghausen’s disease, inflammatory polyps
15-35% are multiple
Slow growing, but can metastasize to regional lymph nodes, liver, bone, skin, thyroid; usually as small, dispersed nodules
Carcinoid syndrome in 1% (20% with widespread metastases) - see below
Duodenum: 2/3 express gastrin, 1/3 of these are associated with Zollinger-Ellison syndrome and are almost always metastatic; may be associated with MEN1
Duodenal carcinoids are less aggressive, usually don’t cause death vs. ampullary carcinoids, Hum Path 2001;32:1252
Other malignant duodenal carcinomas are usually 2 cm+, with increased mitotic figures and muscularis propria invasion
20% produce somatostatin, almost always in Ampulla, usually malignant, often associated with von Recklinghausen’s disease, have glandular structures and psammoma bodies
Ileum: patients with multiple tumors have higher incidence of carcinoid syndrome (22% vs. 2%) and poorer prognosis, AJSP 2003;27:811
Case report with angiomatous polyps simulating Crohn’s disease, Archives 2000;124:450
Case report of metastases to cardiac conducting system, Archives 2002;126:1538
Treatment: surgical excision of tumor and regional lymph nodes, excise solitary liver metastases
5 year survival: 50-65% (85% if confined to bowel wall vs. 5% if serosal invasion)
Gross: tumor protrudes through mucosa as small, polypoid lesion, intact or ulcerated overlying mucosa, buckling of bowel wall; bright yellow after formalin fixation, mean 2 cm
Gross images: multiple tumors, tumor and angiomatous polyposis #1, #2, #3; solitary tumor #1, #2, #3
Micro: submucosal tumor that infiltrates muscularis propria; solid, insular (nesting), trabecular or glandular masses of monotonous small round cells with peripheral pallisading; moderate finely granular cytoplasm, small nucleoli, salt and pepper chromatin; angiolymphatic invasion common, mitotic figures rare; mucin present if glandular pattern; amphicrine cell pattern rare (endocrine and exocrine cells)
Adjacent mucosa in ileal tumors shows angiomatous polyposis (mucosal edema, capillary ectasia, muscularis mucosa hypertrophy, fibrosis / smooth muscle proliferation in lamina propria, club-shaped villi, intramucosal capillary proliferation, although this is not specific for carcinoid tumors), Mod Path 2001;14:821
Micro images: image1, image2, image3, image4, image5, with adjacent angiomatous polyposis #1, #2
Positive stains: keratin, CEA, chromogranin, synaptophysin, Leu7, PAP (rarely), Fontana-Masson (argentaffin reaction)
Negative stains: mucin, S100, CK7, CK20, TTF-1
EM: well formed, membrane bound, dense core secretory granules with dense (osmophilic) cores
Occurs in 1% with carcinoid tumors, 20% with widespread metastases
Elevated levels of 5 hydroxy-indoleacetic acid (5-HIAA), a metabolite, are found in blood and urine
Normally liver deactivates vasoactive amines (serotonin, histamine, bradykinin, others) released from carcinoid tumors; clinical symptoms occur if liver metastases are present or if tumor venous blood flow bypasses the liver
Symptoms: vasomotor disturbances (cutaneous flushes, cyanosis of face and anterior chest, intermittent hypertension), palpitations, intestinal hypermotility (nausea, vomiting, diarrhea, cramps); also asthmatic attacks with bronchospasm, fibrosclerosis of AV and tricuspid valves, elastotic sclerosis of mesenteric vessels causing ischemia, dermal sclerosis, hepatomegaly
Carcinoid heart disease: right sided focal or diffuse plaques of thickened valvular or mural endocardium, that may extend to the great veins, coronary sinus, pulmonary trunk and main pulmonary arteries; tricuspid and pulmonic valves are usually affected by plaque formation; left heart and left sided valves are less frequently affected; endocardial fibrosis is a reaction to serotonin or kinin peptide exposure; plaques are composed of fibroblasts, myofibroblasts and smooth muscle cells embedded in a collagenous matrix, covered by a layer of endothelium; no elastic tissue is present within the plaque
G cell (gastrin) tumors are associated with Zollinger-Ellison syndrome, MEN1 syndrome
D cell (somatostatin) tumors are associated with neurofibromatosis 1 in blacks
Metastases common at diagnosis (21%)
Gross: 0.5 to 2 cm, smooth, round
Micro: resemble carcinoid tumors; often G-cells or D-cells; usually glandular component, psammoma bodies often in D cell tumors
Follicular dendritic cell sarcoma
Rare; first described in 1986 (Am J Pathol 1986;122:562)
Usually presents as painless, indolent mass
May present with pain, but usually no constitutional symptoms
May be associated with Castleman’s disease-hyaline vascular type
Need immunostains for diagnosis
Sites: usually lymph nodes, predominantly cervical, axillary or mediastinal (Am J Hematol 1998;59:161); extranodal sites include oral cavity, spleen, liver, small intestine, pancreas, peritoneum, soft tissue, skin
Poor prognostic factors: large tumor size (6 cm or more), intraabdominal location and coagulative necrosis (Cancer 1997;79:294)
Case reports: Case of the Week #81
Treatment: excision; often recurs locally, occasional distant metastases to liver or lung
Gross images: duodenal mass-10.5 x 10 cm
Micro: storiform arrangement of oval or spindled cells, lymphocytic infiltrate
Micro images: low power; high power #1; #2; CD35
Positive stains: CD21, CD35; occasional S100
Negative stains: desmin, smooth muscle actin, CD117/c-kit
DD: gastrointestinal stromal tumor (CD117+, CD34+, CD21-, CD35-), fibroblastic reticulum cell sarcoma (vimentin+, smooth muscle actin+, desmin+, CD21-, CD35-), interdigitating dendritic cell tumor (S100+, vimentin+, CD21-, CD35-), melanoma or other sarcomas
Gastrointestinal autonomic tumor (GANT)
Variant of gastrointestinal stromal tumors with ultrastructural neural differentiation
Requires EM for diagnosis
Mean age 55 years, usually men
Usually small bowel, mesentery, retroperitoneum
Usually malignant
Gross: >10 cm, well circumscribed, transmural involvement of bowel wall; tan-pink, lobulated, hemorrhagic with necrosis and cystic degeneration
Micro: interlacing spindle cells with minimal pleomorphism, skenoid fibers and myxoid change, 1-2 mitoses/10 HPF
Positive stains: CD117, CD34 (variable), vimentin, NSE
Negative stains: muscle markers
EM: neuron like cells with axonal cytoplasmic processes; synapse like structures; dense core neurosecretory granules
References: AJSP 2001;25:979, AJSP 2002;26:396
Gastrointestinal stromal tumor (GIST)
Differentiates along line of interstitial cell of Cajal, the gut’s pacemaker cell
Median age 67 years, usually > 50 years
May occur in children, be associated with HIV
Malignant tumors metastasize to liver and peritoneum
30-50% are malignant with 5 year survival of 50%
Don’t call GIST if CD117 negative without expert concurrence
Poor prognosis (malignant): over 5 cm, fresh tumor necrosis, extensive hemorrhage unrelated to surgery, hypercellular, marked atypia, 5+ mitotic figures/HPF, smaller cells
High risk: > 1 cm and > 5 MF/50 HPF; also infiltrative border within muscularis propria
Intermediate risk: 1-5 MF/50 HPF and > 1 cm
Low risk: < 1 cm (often are serosal)
Treatment: Gleevec (STI571), which inhibits tyrosine kinases including CD117/c-kit and Abl protein in CML
Gross: often large, bulky, intramural masses; fish-flesh or tan-brown appearance, hemorrhage, necrosis, cystic softening
Micro: usually histologically malignant, usually transmural, usually plump spindle cells with eosinophilic cytoplasm within variably hyalinized or edematous stroma; skenoid fibers (extracellular collagen globules) common; muscle infiltration is common but not predictive of behavior; may have epithelioid morphology
Micro images: duodenal malignant GIST, skenoid fibers, CD117
Positive stains: CD117, CD34, vimentin; variable alpha smooth muscle actin
Negative stains: S100, desmin
Molecular: 36% had c-kit mutations in codon 11
EM: long interdigitating cytoplasmic processes, intercellular junctions, dense core granules
DD: leiomyosarcoma (atypical histology, smooth muscle actin OR desmin positive, CD117-, CD34-, no c-kit mutations), uterine type leiomyomas (attached to colon without wall involvement, resemble benign leiomyoma, actin+, desmin+, CD117-), fibromatosis (may be CD117+ with some antibodies, AJSP 2000;24:947, AJSP 2001;25:549)
References: AJSP 2000;24:1339, Mod Path 2003;16:366, Mod Path 2000;13:1134
GIST-duodenum
Median age 56 years (range 10-88 years)
Associated with neurofibromatosis type 1 (often with multiple tumors)
Poor prognostic factors: >5 cm, > 5 mitoses/50 HPF, epithelioid pattern with mucosal invasion
Good prognostic factors: <2 cm and <5 mitoses/50 HPF; organoid pattern with low cellularity
Often long period to recurrence or metastases
Gross: small intramural or external nodules or large masses extending into retroperitoneum
Micro: usually spindle cell tumors, often with skenoid fibers
Positive stains: CD117, CD34 (54%), smooth muscle actin (39%), S100 (20%)
Negative
stains: desmin (trapped smooth
muscle fibers are positive)
Molecular: c-kit mutations in exon 11 (30%) and exon 9 (13%) are common
References: AJSP 2003;27:625, Mod Path 2003;16:366
May present initially as small bowel mass
DD: bacterial infections (may have positive Leder stain)
Present in GI tract in 50% with AIDS, although symptoms in only 10% (diarrhea, protein-losing enteropathy, abdominal pain)
Gross: multiple red-brown or purple nodules, 5 -15 mm
Micro: spindle cells that expand lamina propria and obliterate muscularis mucosa; extravasated red blood cells; often submucosal
Positive stains: CD34, CD31
Negative stains: S100, desmin, muscle specific actin
Duodenal tumors - mean 54 years old, AJSP 2003;27:625
Gross: intraluminal, bulging, polypoid (duodenal tumors - mean 14 cm)
Gross images: image1
Micro: resemble smooth muscle cells; high grade
Positive stains: smooth muscle actin, desmin
Negative stains: CD34, CD117
Often appear as multiple polypoid tumors causing obstruction or perforation
Usually melanoma, lung and breast carcinoma, choriocarcinoma
Case report of osteosarcoma metastases presenting as a polyp, Archives 2000;124:1682, gross image, micro image#1, #2
Case report of leiomyosarcoma causing intussusception, Archives 2000;124:169, gross/micro images
Gross images: site unspecified
Micro images: contributed by Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina - gall bladder carcinosarcoma metastases #1; #2
Melanoma metastatic to small bowel
Often long period between primary and metastatic diagnosis
Better prognosis if solitary versus multiple metastases
Micro: undifferentiated tumor with discohesive cells with pink cytoplasm, pleomorphic nuclei, macronucleoli, frequent mitotic figures; spindled or epithelioid cells
Micro images: contributed by Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina - melanoma from thigh of 50 year old Bosnian man, metastatic to jejunum - #1; #2; #3; S100; MelanA;
Positive stains: S100, HMB45, MelanA/Mart1
Negative stains: CD117, CD34, smooth muscle actin
Associated with endometriosis and unopposed estrogen therapy, AJSP 2000;24:513
Micro: proliferation of endometrioid glands and stroma with stromal condensation around glands, mild to moderate cytologic atypia of stroma and stromal mitoses; may have stromal pseudodecidualization, focal epithelial atypia; no definite malignant epithelial features
Due to production of gastrin that enters systemic circulation by gastric, pancreatic or peripancreatic carcinoids
May be very small and difficult to detect
Micro: variable villus abnormality with increased chronic inflammatory cells and neutrophils in lamina propria; may have surface erosions; also gastric foveolar metaplasia of duodenum; may be normal by H & E but abnormal by EM
Miscellaneous
Does not apply to carcinoid tumors, lymphoma or sarcoma OR tumors in ileocecal value, Ampulla of Vater or Meckel’s diverticulum
Primary tumor (T)
TX: primary tumor cannot be assessed
T0: no evidence of primary tumor
Tis: carcinoma in situ (intraepithelial lesions)
T1: tumor invades lamina propria or submucosa
T2: tumor invades muscularis propria
T3: tumor invades through the muscularis propria into the subserosa, or into nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less *
T4: tumor perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas)
* Note: the nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, part of the retroperitoneum
Regional lymph nodes (N)
NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastasis
N1: regional lymph node metastasis
Note: involvement of the celiac nodes is considered M1 disease
Distant Metastasis (M)
MX: distant metastasis cannot be assessed
M0: no distant metastasis
M1: distant metastasis
Stage grouping
Stage 0: Tis N0 M0
Stage 1: T1-T2 N0 M0
Stage 2: T3-T4 N0 M0
Stage 3: Any T N1 M0
Stage 4: Any T, any N, M1
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Tumor location
Histologic type
Histologic grade if relevant (well differentiated: >95% glands, moderately: 50-95% glands, poorly: 5-49% glands, undifferentiated: <5% glands)
Tumor size
Extent / depth of invasion
Margin involvement (proximal, distal, radial [soft tissue closest to deepest tumor penetration]), and distance of tumor to margin
Invasion of other structures
Obstruction, perforation, ulceration, proximal dilation
Nuclear grade, presence of necrosis
Angiolymphatic invasion
Other pathologic findings (polyps, Crohn’s disease, celiac disease)
Nodal involvement (# involved, # identified)
Results of special studies
References: Archives 2000;124:46
End of Small Bowel chapter