Colon-nontumor
Last revised 8 June 2009
Copyright (c) 2003-2009, PathologyOutlines.com, Inc.
See also Colon-tumor, Anus and perianal area
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Table of contents
Primary references, embryology, normal anatomy, normal histology, normal physiology, bowel preparation changes
Congenital anomalies: atresia, chronic intestinal pseudo-obstruction, cyst of retrorectal space, duplication, epidermolysis bullosa dystrophica, gastroschisis, heterotopia, Hirschsprung’s disease, intestinal neuronal dysplasia, malrotation, omphalocele
Diverticular disease: diverticulosis, diverticulitis
Inflammatory bowel disease: general, Crohn’s, Crohn’s-carcinoma, indeterminate colitis, ulcerative colitis, dysplasia, UC-carcinoma, ulcerative proctitis, diffuse giant inflammatory polyposis
Colitis (non-infectious): general, diarrhea/dysentery-general, active, allergic, antibiotic-associated, Behcet’s, Brainerd diarrhea, collagenous, diversion, diverticular disease related, eosinophilic, graft vs. host disease, granulomatous, hemorrhagic, ischemic, Kayexalate associated, lymphocytic, lymphoid follicular proctitis, malakoplakia, mastocytic, necrotizing enterocolitis, NSAID, pouch related, radiation, talc, typhlitis
Infectious colitis (specific microorganisms): actinomycosis, adenovirus, amebic, balantidiasis, basidiobolomycosis, Campylobacter, Candida, Chagas disease, Clostridium botulinum, CMV, Cryptosporidium, E coli, Fasciola, histoplasmosis, HIV, HSV, infectious (acute self limited), mycobacteria, rotavirus, Salmonella, Schistosomiasis, Shigella, spirochetosis, Strongyloides, syphilis, trichuriasis, tuberculosis, typhoid fever, Vibrio cholera, Yersinia
Non-neoplastic, non-congenital lesions: adhesions, amyloidosis, angiolymphoid hyperplasia with eosinophilia, barium granuloma, blue/green colon, brown bowel, colchicine toxicity, colitis cystica profunda, endometriosis, fibrosing colonopathy, florid vascular proliferation, gastric heterotopia, gout, hemorrhoids, hyperplastic pacinian corpuscle, idiopathic constipation/cathartic colon, infarct, infarcted epiploic appendages, melanosis coli, pneumatosis cystoides intestinalis, reactive angioendotheliomatosis, solitary rectal ulcer, vascular ectasia, vasculitis, volvulus, xanthelasma
Go to Colon-tumor chapter - polyps, polyposis syndromes, tumors, grossing, staging, features to report
Primary references
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP), Jan 1975 to July 2006
American Journal of Surgical Pathology (AJSP), March 1977 to July 2006
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to July 2006
Human Pathology (Hum Path), March 1970 to July 2006
Journal of Clinical Pathology, January 1966 to May 2006
Modern Pathology (Mod Path), January 1988 to June 2006
Biomed Center, to 12 July 2006
Mills: Sternberg's Diagnostic Surgical Pathology (4th ed), 2004
Rosai: Rosai and Ackerman's Surgical Pathology (9th ed), 2004
Websites with images: PathoPic, PEIR digital library
Please refer to these primary references for more detailed discussions and photographs
Primitive gut is divided into foregut, midgut and hindgut
Midgut gives rise to cecum, ascending colon and right 75% of transverse colon (also distal duodenum to ileum)
Hindgut develops into remainder of transverse colon to ano-rectal line
Micro images: fetal colon-various images
References: more information, Early Hum Dev 2004;78:1
Normal anatomy of colon
1.0 to 1.5 meters long, from terminal ileum to anal canal
Compared to small intestine, has greater diameter, fixed position, epiploic appendages, taeniae coli (discontinuous muscular fibers)
Regions: cecum, ascending (right sided) colon, transverse colon, descending (left sided) colon, sigmoid colon, rectum
Diagram: regions of colon
Cecum: in peritoneum, 6 x 9 cm; large blind pouch arising from proximal right colon; blind end directed downward, open end directed upward
Drawing: cecum and appendix; cecum and ileocecal valve #1; #2
Ascending colon: 15-20 cm long; posterior surface is in retroperitoneum, but anterior and lateral surfaces have serosa and are intraperitoneal
Hepatic flexure: junction of ascending and transverse colon
Splenic flexure: junction of transverse and descending colon
Descending colon: 10-15 cm long; posterior surface is in retroperitoneum, but anterior and lateral surfaces have serosa and are intraperitoneal
Sigmoid: descending colon at origin of mesosigmoid; from pelvic rim to S3 vertebra
Drawing: sigmoid and anal valves
Rectum: 12 cm; sigmoid colon from termination of mesosigmoid; also from opposite sacral promontory to upper border of anal canal; becomes extraperitoneal (within the pelvis) as it passes between the crura of the peritoneal muscles; has no serosa / peritoneal covering
Drawing: rectum and anal canal
Micro images: rectum; rectal folds of Morgagni
Pouch of Douglas: cul-de-sac in women made up of reflection of peritoneum from the rectum over the pelvic wall
Drawings: rectovaginal (RV) pouch
Taenia coli: discontinuous muscular fibers
Micro images: Taenia coli and lymphoid tissue; transverse section; relationship to muscularis propria
Epiploic appendages: pedunculated fat on lateral colon; lined by mesothelium
Gross images: see tip of pointer
Vasculature
Superior mesenteric artery supplies cecum to splenic flexure
Inferior mesenteric artery supplies remainder of colon to rectum
Numerous collaterals connect mesenteric circulation with celiac arterial axis proximally and pudental circulation distally
Superior hemorrhoidal branch of inferior mesenteric artery supplies upper rectum; hemorrhoidal branches of internal iliac or internal pudental artery supplies lower rectum
Venous drainage is similar; there is an anastomotic capillary bed between the superior and inferior hemorrhoidal veins, providing a connection between the portal and venous systems
Drawings: vessels of rectum
Normal histology of colon
Composed of mucosa, submucosa, muscularis propria (externa) and serosa (perimuscular tissue in rectum)
Micro images: low power; various images
Virtual slides: normal colon
Mucosa: epithelium, lamina propria and muscularis mucosa
Epithelium: low columnar to cuboidal cells
Tubules are tightly packed, have straight test tube shape (minimal branching), parallel to each other, straight luminal surface, rest on thin basement membrane, extend to muscularis mucosa; absorptive cells and goblet cells
Crypts open into surface epithelium or into innominate grooves
Crypts are surrounded by pericryptal fibroblast sheath (fibroblasts or myofibroblasts)
Crypts also contain precursor cells, endocrine cells and Paneth cells in right sided colon
Positive stains: CDX2 (sensitive and specific for colon), CK8, CK18, CK19
Micro images: mucosa #1; #2; #3; #4; #5; #6; crypts
pericryptal fibroblast sheath - #1 (figures C/D); #2-A: sheath is positive for high molecular weight caldesmon; #3-A: sheath is positive for alpha smooth muscle actin;
References: J Clin Pathol 1999;52:785 (pericryptal fibroblasts)
Innominate grooves: mucosal area where several crypts open into one central crypt
Lamina propria: capillaries (uniform), lymphatics just above muscularis mucosa; inflammatory cells present (see below)
Muscularis mucosa: thin and regular
Micro images: mucosa and muscularis mucosa #1; #2
Submucosa: loose connective tissue with submucosal plexus of Meissner; minimal inflammatory infiltrate; younger patients may have intramucosal lymphoid aggregates that disrupt muscularis mucosa
Micro images: mucosa and submucosa #1; #2; submucosal plexus of Meissner
Muscularis propria: inner circular layer, myenteric plexus of Auerbach, outer longitudinal layer
Micro images: muscularis propria #1; #2; myenteric plexus of Auerbach #1; #2; #3
Serosa: single layer of flat to low cuboidal mesothelial cells and adjacent fibroelastic tissue
Types of cells
Absorptive cells: basal nuclei, eosinophilic cytoplasm, no mucin, shorter microvilli than small intestinal cells
Endocrine cells: usually at base of crypts; similar to cells in pancreas, lung, thyroid, urethra; contain fine eosinophilic granules with secretory proteins; nuclei are not basal but on luminal side of granules
Secretory granules are released at BASAL surface of endocrine cell or along lateral surface; NOT apical; products modulate digestive functions
Ganglion cells: nerve cell body (perikarya) common in normal and abnormal mucosa; may resemble microgranulomas or CMV (AJCP 2005;124:269)
Goblet cells: contain ovoid mucoid vacuole
Inflammatory cells: lymphocytes (B & T), intraepithelial lymphocytes only rarely, plasma cells, histiocytes (may contain hemosiderin, mucin or “pseudomelanin” from laxatives), mast cells, occasional eosinophils (vary by geography, Mod Path 1997;10:363); lymphoglandular complexes when lymphoid follicles surround deep crypt epithelium extending into submucosa; neutrophils not normally present
Interstitial cells of Cajal: associated with myenteric (Auerbach/intramuscular) plexus between circular and longitudinal muscle layers; have pacemaker function which facilitates active propagation of electrical events and mediates neurotransmission; have unique ultrastructure on EM with gap junctions between each other and smooth muscle cells; have surface tyrosine kinase receptor c-Kit (CD117) which is essential for their development; kit ligand provided by neuronal cells or smooth muscle cells
Reference: AJSP 2003;27:228
M cells: flattened surface cells overlying lymphoid aggregates; associated with mononuclear inflammation and epithelial cells with reduced cells; deliver intact foreign macromolecules and commensal bacteria from lumen to mucosal lymphoid tissue to trigger immune responses; also site of adhesion and invasion for enteric pathogens (Histopathology 1987;11:941), including HIV (Pathobiology 1998;66:141) and Shigella (Ann NY Acad Sci 1994;730:197)
M cells have cytoplasmic microvilli, enfold lymphocytes and plasma cells (Dig Dis Sci 1992;37:1089)
Drawings: M cells
Micro images: small intestine
Paneth cells: secretory epithelial cells at base of crypts in cecum and ascending colon; considered metaplastic if present elsewhere in colon; granules contain antimicrobial peptides (Trends Microbiol 2004;12:394)
Micro: basophilic cytoplasm (due to rough ER) and numerous eosinophilic granules, larger than those in endocrine cells
Micro images: Paneth cells #1; #2; #3; #4; #5
Undifferentiated crypt cells: at base of crypts; precursor to other noninflammatory cells; migration from crypts to surface takes 3-8 days; process allows for rapid repair, but also makes cells sensitive to radiation and cancer chemotherapy
Normal physiology of colon
Reclaims water and electrolytes
Intestinal immune system
Composed of Peyer’s patches in ileum, M cells (membranous) in small intestine and colon which transfer antigen macromolecules from lumen to lymphocytes, T cells and B cells, and mucosal associated lymphoid tissue - lymphoid nodules, mucosal lymphocytes, appendix lymphoid follicles and mesenteric nodes
Neuromuscular function
Anterograde and retrograde peristalsis mixes food, promotes maximal contact of nutrients with mucosa
Colonic peristalsis prolongs contact with mucosa
Peristalsis mediated via enteric nervous system, smooth muscle layers and interstitial cells of Cajal
Gut innervation has complex 3D structure
Bowel preparation associated changes
Micro: reduced intracellular mucin, epithelial apoptosis and sloughing, increase in mitotic figures; may have erosion of superficial epithelium, consistent with clinical impression of aphthoid ulcer; also increased lymphocytes and neutrophils (Dis Colon Rectum 2006;49:109); rarely lamina propria edema or extravasated red blood cells
DD: Crohn’s disease
References: Hum Path 1998;29:972
Congenital anomalies
Atresia of colon
Imperforate mucosal diaphragm or stringlike segment of bowel
Very rare (1 per 20,000 live births)
Associated with other congenital anomalies, including Hirschsprung’s disease
May have genetic (J Pediatr Surg 2005;40:390) or vascular cause
Type 1: bowel and mesentery are intact, but bowel lumen is interrupted by a complete membrane
Type 2: bowel is discontinuous, connected by a fibrous cord
Type 3: bowel ends are completely separated and mesentery has a gap
Case reports: #1
Treatment: segmental resection and anastomosis; good prognosis with prompt treatment (J Pediatr Surg 2005;40:1258)
Gross images: atretic and dilated segments
References: eMedicine
Chronic intestinal pseudo-obstruction
Syndrome of intestinal obstruction without mechanical obstruction
Usually a small bowel disorder but can occur anywhere in GI tract
Gut motility depends on sympathetic (thoracolumbar) and parasympathetic (vagal) innervation to the ganglionated plexi; also enteric nervous system, smooth muscle cells and interstitial cells of Cajal
Usually congenital in children; in adults due to systemic disease (diabetes, myxedema, dermato/polymyositis, amyloid, Chagas disease, myotonic dystrophy, muscular dystrophy, scleroderma), drugs (antiParkinson, clonidine, ganglionic blockers, tricyclic antidepressants, phenothiazines) or idiopathic (ceroidosis, cathartic colon, Hirschsprung’s disease, visceral myopathies, visceral neuropathies)
May be due to loss of interstitial cells of Cajal in small and large bowel (AJSP 2003;27:228)
Often poor long-term outcome (Clin Gastroenterol Hepatol 2005;3:449); high mortality if perforation or ischemia
Ogilvie's syndrome (acute colonic pseudo-obstruction): abrupt onset of abdominal distension (Radiol Med (Torino) 2005;109:370)
Treatment: diet, octreotide, surgery, transplant
Micro: visceral myopathy - vacuolar degeneration with swelling and loss of muscle cells, fibrosis of outer longitudinal muscle layer; other cases show cytoplasmic vacuoles, marked nuclear enlargement and irregularity and interstitial fibrosis (AJSP 1987;11:846)
Micro images: familial autonomic visceral myopathy - muscularis propria degeneration #1-especially inner layer; #2-with muscle fiber loss and degenerative changes and collagen replacement; muscularis mucosa shows degenerative changes of fibers (vacuolation and pyknotic nuclei)
DD: ischemic colitis (hemosiderin deposits, fibrous stricture), tuberculosis (stricture, necrotizing granulomas), scleroderma (patchy bowel involvement, dense fibrosis affecting inner or all muscle layers, no vacuolar change)
References: J Clin Pathol 1988;41:424-inherited, Eur J Pediatr Surg 2003;13:201-mitochondrial myopathies
Also called tailgut cyst
Retrorectal space is loose areolar tissue plane between fascia propria of rectum and presacral space
Rare; often misdiagnosed clinically (J Am Coll Surg 2003;196:880)
Dermoid cyst: unilocular, lined by squamous epithelium and skin adnexae, no smooth muscle
Epidermoid cyst: unilocular, lined by squamous epithelium without adnexa
Rectal duplication cyst: unilocular, lined by colonic, gastric or respiratory epithelium with organized smooth muscle similar to muscularis propria
Cystic hamartoma: multilocular with squamous, transitional or glandular lining, disorganized smooth muscle, occasionally foreign body granulomatous inflammation; case report diagnosed as ovarian tumor (Arch Gynecol Obstet 2005;272:301)
Treatment: complete excision recommended to prevent malignant transformation (AJCP 1988;89:139)
Gross: multilocular, variable solid areas
Micro images: cystic hamartomas; dermoid cyst; epidermoid cyst; tailcut cyst
References: Radiographics 2001;21:575-adults, Archives 2000;124:725-cystic hamartoma
Duplication of colon
Rare; partial or complete doubling of a variable length of bowel
Saccular to long, cystic structures
Often present in mesentery of normal bowel without communication with lumen
Associated with complex GU abnormalities
May rarely present in adults with rectal bleeding (World J Gastroenterol 2005;11:5072)
May not require treatment (Yonsei Med J 2005;46:189)
Gross images: double colonic lumen; various images
Courtesy of Dr. Celso Rubens Vieira e Silva, Brazil: cystic congenital duplication - gross; micro
DD: enteric cysts (less organized smooth muscle, no nerve plexus)
References: eMedicine (GI duplications)
Epidermolysis bullosa dystrophica in colon
Commonly causes constipation
Case reports: fecal impaction causing toxic megacolon and death from perforation (BMC Dermatol 2006;6:2)
Gastroschisis
Portion of abdominal wall fails to form together, with extrusion of intestines, but NOT through the umbilical cord
Intestines are exposed, not covered by a membranous sac, as in omphalocele
Associated with intestinal atresia, Hirschsprung’s disease
References: eMedicine
Heterotopia of colon
Pancreatic or gastric mucosa appear as nodules (usually small) in aberrant gut location
Case reports: gastric heterotopia associated with adenoma in elderly patient (NJ Med 1995;92:512), gastric heteropia #1 with hemorrhage (Gut 1988;29:848), #2 in rectum (Archives 1999;123:222), child with heterotopic renal tissue in colonic wall associated with congenital anomalies (Pediatr Dev Pathol 2002;5:587), skin heterotopia in polyps, associated with trauma (Dis Colon Rectum 1995;38:219)
Micro images: gastric and colonic mucosa; prominent parietal cells
Hirschsprung’s disease of colon
top
Also called congenital aganglionic megacolon
No parasympathetic ganglion cells in submucosal and myenteric plexus of affected colon, causing functional obstruction and colonic dilation proximal to affected segment
80% male; usually sporadic (1 per 5,000 live births); in 3.6% of affected siblings
10% have Down’s syndrome; another 5% have other serious neurologic impairment
Normally, neural crest cells migrate into bowel, forming intestinal neural plexus; in Hirschsprung’s, usually are heterogeneous defects in genes regulating migration and survival of neuroblasts (endothelin 3 and its receptor), glial cell-derived growth factor (neurogenesis) and receptor tyrosine kinase activity (RET, Ann Med 2006;38:11)
Always affects rectum, usually also sigmoid, not other segments; anus and rectum usually small and devoid of stool
Symptoms: failure to pass meconium, obstructive constipation; may have occasional passage of stool or diarrhea if only a short segment of rectum is affected
Complications: proximal innervated colon may become massively distended (15 cm in diameter) with muscular wall hypertrophy and rupture/perforation, usually near cecum or appendix; also acute intestinal obstruction, enterocolitis with fluid and electrolyte imbalance
Mortality: currently 5-10%
Classic: aganglionic portion begins in distal colorectum and extends a considerable distance proximally
Ultrashort segment: less than 2 cm affected in rectum and sigmoid; more common in boys; difficult to document because this portion of rectum typically lacks ganglion cells even in normals
Short segment: aganglionic portion involves rectum and rectosigmoid for only a few cm
Long segment: 10% of cases; involves 40 cm or more of colon, and may extend into small bowel; patients have obstruction without megacolon; more common in girls; may lack hypertrophied nerve trunks, but do have increase in acetylcholinesterase+ nerve abnormalities
Zonal colonic aganglionosis: involvement of short segment of bowel; ganglion cells are present above and below this segment
Diagnosis: mucosal rectal biopsy with serial sections to detect ganglion cells (more irregular in submucosal plexus but process is less invasive than full thickness rectal biopsy [classic method below]); further identify in frozen section stained with acetylcholinesterase (see below); other diagnostic tests are contrast enema and anorectal manometry (J Pediatr Gastroenterol Nutr 2006;42:496)
Classic method: biopsy muscular wall of rectum and examine for ganglion cells in myenteric plexus; should biopsy 2+ cm above anal valve in infants, 3+ cm in older children; if squamous epithelium present, must biopsy higher
Frozen sections: to document absence of ganglion cells and determine level of bowel transaction at surgery; also for acetylcholinesterase staining
Treatment: proctectomy with pull-through of ganglionic bowel to anus; some patients have persistent bowel dysfunction (enterocolitis, constipation, incontinence)
Gross: normal anus but small rectum and anal canal without stool, dilated proximal bowel
Gross images: dilated bowel #1; #2; #3
Micro: no ganglion cells in submucosal or myenteric plexus; thickening and hypertrophy of nonmyelinated nerve fibers and muscularis mucosa; stercoral ulcers (sharply demarcated shallow ulcers with mucosal inflammation due to pressure of feces on obstructed colon); fibromuscular dysplasia of arteries between normal and diseased colon; no/reduced myenteric and muscular interstitial cells of Cajal in rectosigmoid colon
Hypoganglionosis - arises between normal and aganglionic bowel; reduced number of ganglion cells (such as 10% of normal)
Micro images: lack of ganglion cells #1; #2; hyperplastic nerves but no ganglion cells #1; #2; increased acetylcholine positive nerve fibers #1; #2; reduced interstitial cells of Cajal
normal ganglion cells - sympathetic ganglion cells; dorsal root of spinal cord #1; #2
Virtual slides: Hirschsprung’s disease
Positive stains: acetylcholinesterase (increase in staining in lamina propria and muscularis mucosa reflects increase in nerve fibers (Pediatr Surg Int 2005;21:255)
Negative stains: neuron specific enolase (stains ganglion cells), RET (detects ganglion cells, AJCP 2006;126:49)
EM: altered cytoskeletal proteins in affected colon
References: Archives 2002;126:928, Archives 2002;126:692, eMedicine, OMIM 142623 and 600155
Intestinal neuronal dysplasia
Also known as neuronal colonic dysplasia, hyperganglionosis, pseudo- or variant Hirschsprung’s disease
Type A: hypoplastic or aplastic sympathetic innervation
Type B: hypoplastic or plastic parasympathetic innervation (Virchows Arch A Pathol Anat Histopathol 1992;420:171)
Associated with neurofibromatosis 1 and MEN2b syndromes
Associated with hypoganglionosis of myenteric plexus or aganglionosis of rectum
A controversial entity; should diagnose only if no other diagnosis, no obstruction, and multiple adequate biopsies (30 sections) of submucosa and muscularis propria available; may be due to delayed maturity of enteric nervous system as 95% have normal gut motility within 1 year
Diagnostic criteria in two studies: (1) biopsies 8-10 cm above dentate line, sufficient submucosa, 15-20% of ganglia are giant ganglia with more than 8 nerve cells in submucosa of 30 serial sections (Eur J Pediatr Surg 2004;14:384); (2) hyperganglionosis of submucous plexus, giant ganglia and rectal biopsies show either ectopic ganglia, increased acetylcholinesterase activity in lamina propria or increased acetylcholinesterase in nerve fibers around submucosal blood vessels (J Pediatr Surg 2001;36:777)
Case reports: coexisting congenital interstitial cell of Cajal hyperplasia (AJSP 2000;24:1568)
Micro: resembles Hirschsprung’s disease with hyperplasia of myenteric nerves and increased acetylcholinesterase staining, but with occasional (15-20%) submucosal giant ganglia (containing 7-10 neurons vs. 3-5 normally) and isolated ganglion cells in submucosa
Note: giant ganglia by themselves are not specific (Virchows Arch 1998;432:103)
Micro images: various images
Malrotation of colon
From improper embryologic rotation of gut
Symptoms may first occur in women during pregnancy (Obstet Gynecol 1993;81:817)
Drawings: Netter drawings; various drawings and text
References: eMedicine
Omphalocele
Abdominal musculature fails to form
Infant is born with herniated abdominal contents into ventral membranous sac through the umbilical cord
Case reports: with colonic atresia and Hirschsprung’s disease (Pediatr Surg Int 2001;17:218)
Gross images: omphalocele #1; #2; various images
DD: gastroschisis (not through umbilical cord, no membranous sac covering intestines)
References: eMedicine #1; #2
Diverticular disease of colon
Diverticulosis
Diverticulum: blind pouch leading off alimentary tract, lined by mucosa that communicates with gut lumen
Congenital: have all 3 layers of bowel wall (includes Meckel’s diverticulum)
Acquired: lack or have attenuated muscularis propria due to focal weakness in wall and increased intraluminal pressure
Note: colonic longitudinal layer is gathered into taeniae coli; focal defects occur where nerves and arterial vasa recta penetrate inner circular muscle wall
Associated with Western diets (low fiber causes prolonged transit time and increased intraluminal pressure associated with low volume stools); rare in Asia, Africa, South America where high residue diet is common, and may diminish colonic segmentation and associated mucosal herniation
Rare before age 30, 50% of cases are in patients age 60+; only 20% develop symptoms
May regress early in development or become more numerous/prominent over time
May coexist with inflammatory bowel disease in some patients
Left sided disease: common in West, affects sigmoid but not rectum, older individuals
Right sided disease: more common in Far East, may mimic appendicitis; in Japan, has similar features to left-sided disease (Int J Colorectal Dis 2002;17:365); other reports indicate patients may be younger with fewer clinical problems (Dis Colon Rectum 1995;38:755)
Symptoms: cramping, discomfort, constipation, distention, sensation of inability to completely empty rectum; alternating constipation and diarrhea; motor abnormalities may be due to loss of interstitial cells of Cajal and glial cells (J Clin Pathol 2005;58:973)
Complications: hemorrhage (may be massive), perforation with abscess resembling a mass or forming a sinus tract, diverticulitis / peritonitis, fistula into bowel or bladder, obstruction, adhesions
Treatment: high fiber diet and poorly absorbed antibiotics (Digestion 2006;73 Suppl 1:58), resection for perforation and peritonitis and for repeated attacks of diverticulitis
Grossing: fix intact specimen with formalin for 24 hours before dissection
Gross: multiple, small, flasklike invaginations present along prominent taeniae coli, filled with mucin or stool but easily emptied, may bulge into serosa; thick and corrugated circular muscle with prominent accordion-like mucosal folds; in severe cases, bowel is segmented and shortened
Gross images: multiple diverticula #1; #2; #3; #4; #5; #6; #7; with bowel wall stenosis; blue-gray diverticula #1; #2
Micro: no muscle layer around diverticula except for residual bundles of muscularis mucosa; inflammation due to obstruction or perforation, may dissect into adjacent pericolic fat, causing fibrotic thickening resembling colon carcinoma; may have Paneth cells
Micro images: mucosal herniation through thinned muscularis propria; central lumen with surrounding mucosa #1; #2; Paneth cells #1; #2
Virtual slides: diverticulum
DD: Crohn’s disease if fistulas present (has mucosal ulceration, lymphoid aggregates distant from inflamed diverticula)
References: AJCP 1997;107:438
Diverticulitis
Radiologically may resemble carcinoma
Clinically may resemble appendicitis
May be more aggressive in younger patients (World J Gastroenterol 2006;12:2932)
Treatment: liquid diet (bowel rest) and oral antibiotics; surgical resection if perforation, fistula, obstruction, persistent pain, hemorrhage, repeated attacks or immunocompromise (J Clin Gastroenterol 2006;40:S145)
Gross images: hyperemia #1; #2; acute diverticulitis; acute and chronic disease; diverticulitis with perforation #1; #2
Micro: acute or chronic inflammatory infiltrate near base of diverticula; occasionally granulomatous inflammation
Micro images: low power; medium power #1; #2; vegetable fiber in granulation tissue #1; #2 (with polarization); fecal granuloma associated with perforation #1; #2; #3
Virtual slides: diverticulitis due to Actinomyces
DD: Crohn’s disease (although both may coexist)
References: eMedicine #1; #2
Inflammatory bowel disease (IBD)
Inflammatory bowel disease-general
Chronic, relapsing, inflammatory disorders of unknown origin
Incidence increasing in children (World J Gastroenterol 2006;12:3204)
Frequently have extra-intestinal manifestations (World J Gastroenterol 2005;11:7227)
Incidence increasing in Asian Pacific countries (Curr Opin Gastroenterol 2005;21:408)
15% have affected first degree relatives; 9% lifetime risk if parent or sibling is affected
Associated with HLA-B27
Often coexists with diverticular disease; the presence of Crohn’s in diverticular disease is suggested by fissuring ulcers, ulcers outside areas of active diverticulitis and fistulas other than colovesicle or colovaginal; most patients don’t develop other IBD lesions
AMACR expression is increased in dysplastic epithelium in IBD (AJSP 2006;30:871)
Possible causes: alteration in usual steady state between immune system (activated by microbes, antigens and endogenous inflammatory stimuli) and host defenses that maintain integrity of mucosa and down-regulate inflammation (Inflamm Bowel Dis 2006;12:S3, Nat Clin Pract Gastroenterol Hepatol 2006;3:390)
Diagnosis: requires clinicopathologic correlation; pathologist should convey histologic findings to clinician, who correlates with clinical history, endoscopy, radiology; disease may be difficult to classify (Histopathology 2006;48:116)
Treatment: immunosuppressive therapy
Crohn’s disease of colon
Transmural granulomatous disease affecting GI tract from esophagus to anus but discontinuous
Also called regional enteritis because it affects sharply delineated segments, or granulomatous colitis due to granulomas
Primarily affects Western populations with prevalence of 3 per 100,000, peaks in teens/twenties and at ages 50-69
More common in whites (HLA-DR1/DQw5), Jews, smokers; monozygotic twins have 30-50% concordance
Usually involves small intestine; 40% of patients have colon involvement
Symptoms: episodic mild diarrhea, fever, pain; may be precipitated by stress; if colon affected, may have anemia
20% have abrupt onset of symptoms resembling acute appendicitis or bowel perforation
Extra-intestinal symptoms: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, clubbing of fingertips, primary sclerosing cholangitis (not as common as with ulcerative colitis); occasionally uveitis, pericholangitis and renal disorders secondary to periureteral fibrosis
Complications: fibrosing strictures (common in terminal ileum); fistulas to loops of bowel, bladder, vagina and perianal skin; also protein losing enteropathy, generalized malabsorption, Vitamin B12 deficiency, bile salt malabsorption with steatorrhea, toxic megacolon (4%), carcinoma (see below)
Treatment: medical therapy (steroids, antibiotics); may need surgery eventually, although Crohn’s often recurs in pouch; involvement of resection margins doesn’t correlate with recurrence
Gross: dull and granular serosa, creeping fat (mesenteric fat wraps around bowel surface), thick/rubbery intestinal wall (due to edema, inflammation, fibrosis, hypertrophy of muscularis propria), strictures (string sign on barium enema), sharp demarcation of affected segments from uninvolved bowel (skip areas)
Aphthous mucosal ulcers coalesce into long, serpentine linear ulcers along bowel axis to acquire cobblestone appearance; fissures in mucosal folds lead to fistulas or sinus tracts
Usually rectal sparing; disease overall is less severe in distal vs. proximal colon (i.e. preferential right-sided involvement)
Gross images: long linear ulcers #1; #2; cobblestone pattern #1; #2; stenotic lumen #1; #2 with creeping fat; various images
Micro: superficial or deep ulceration with adjacent granulation tissue extending into deep submucosa or below; transmural inflammation with lymphoid aggregates throughout bowel wall; sarcoid-like, non-caseating, poorly formed granulomas in all tissue layers (50-70% of cases, may need serial sections to detect), usually adjacent to blood vessels or lymphatics, disease is focal with intervening normal mucosa in bowel and throughout GI tract (mouth to anus); goblet cells present; initially focal neutrophils in epithelium and overlying lymphoid aggregates and plasmacytosis, then cryptitis, crypt abscesses, but usually no neutrophils in lamina propria
Mucosa and submucosa are also edematous
Often reduplication of muscularis mucosa in diseased segments, fibrosis, and thickened bowel wall; may have neuronal hyperplasia; variable Paneth cells and pyloric gland metaplasia
Aphthous ulcer: lymphoid follicle with surface erosion
Note: Crohn’s disease of colon resembles ulcerative colitis, but Crohn’s also has fistulas / sinus tracts, skip lesions, deep ulcerations, marked lymphocytic infiltration, serositis, granulomas, fewer plasma cells
Definitive diagnosis (per Sternberg): transmural lymphoid aggregates in areas not deeply ulcerated, nonnecrotizing granulomas; suggestive features are skip lesions, linear ulcers, cobblestoning, fat wrapping or terminal ileum inflammation
Often requires multiple biopsies; difficult to diagnosis without terminal ileum involvement
Other diagnostic criteria: transmural lymphoid aggregates in areas that are not deeply ulcerated or nonnecrotizing granulomas
Micro images: transmural inflammation #1; #2; #3; #4; granulomas #1; #2; #3; #4; #5; #6; #7; #8; crypt abscess #1; #2; crypt abscesses and granuloma; inflammation of vessel wall; transmural inflammation
Virtual slides: Crohn’s colitis
DD: ulcerative colitis (abnormal rectal biopsy, not transmural, no fissures / fistulas, no granulomas but occasionally may have granulomas around ruptured cysts; may have patchy disease, ileal inflammation, aphthous ulcers or transmural inflammation), ischemic bowel disease, tuberculosis
References: Mod Path 2003;16:347, Wikipedia, eMedicine #1, #2
Crohn’s disease associated carcinoma in colon
Preceded by same dysplastic changes as in ulcerative colitis
May occur in out of circuit or bypassed segments
Reported risk of colon carcinoma varies from minimal (Aliment Pharmacol Ther 2004;19:287) to less than 1% (Hepatogastroenterology 2000;47:57) to 3% (Cancer 2001;91:854); carcinoma present in 3% of colons resected for severe Crohn’s colitis (Dis Colon Rectum 2006;49:950)
Risk factors are long duration and severe disease; screening colonoscopy is recommended (Gastroenterology 2001;120:820)
Diagnosis is usually made endoscopically as a gross intraluminal lesion, usually solitary; tumor has better prognosis than ileal carcinomas, similar to other colonic carcinomas with same stage
Case reports: mixed adenocarcinoma-carcinoid tumor (J Clin Pathol 1993;46:183)
Indeterminate colitis
Diagnosis when cannot distinguish between Crohn’s and ulcerative colitis (J Clin Pathol 1978;31:567-original designation)
Not a specific disease entity as it has no diagnostic criteria
5-15% of cases of inflammatory bowel disease; up to 30% of pediatric cases (Inflamm Bowel Dis 2006;12:258)
Originally related to fulminant colitis requiring emergent colectomy, in which classic features of ulcerative colitis or Crohn’s disease were obscured by severe ulceration with early superficial fissuring, transmural lymphoid aggregates and relative rectal sparing
Currently often used when definitive diagnosis cannot be made at colonoscopy, biopsy or colectomy
Most patients evolve to a definite diagnosis at follow up
Pouch complication (43%) and removal (10%) rates are less than Crohn’s disease, more than ulcerative colitis (Dis Colon Rectum 2005;48:1542)
Pediatric cases rapidly progress to pancolitis
Gross images: relative distal sparing in fulminant disease; longitudinal ulcers in refractory disease
Micro images: associated with fulminant disease - mild architectural changes and inflammation; deep ulcers; undermining ulcers; aphthoid-like ulcers at the bases of innominate grooves
other - crypt associated granulomas may be a reaction to mucin extravasation
References: J Clin Pathol 2004;57:1233
Dysplasia in inflammatory bowel disease
Usually detected by surveillance colonoscopy with biopsy
Multiple biopsies recommended for diagnosis of flat lesions
Precedes carcinoma in almost all cases
Incidence of dysplasia is 5% after 10 years of UC, 25% after 20 years of UC
Dysplasia is rare (less than 3%) in retained rectal segment after anastomosis
Risk may be reduced by 5-aminosalicylate use (Am J Gastroenterol 2005;100:1345)
Recommendations for biopsy interpretation: either negative for dysplasia, positive for dysplasia or indefinite for dysplasia
Treatment: colectomy if flat high grade dysplasia (confirmed by another pathologist or another biopsy) or possibly multifocal low grade dysplasia
Adenoma: assume adenomatous changes represent inflammatory bowel disease associated dysplasia; treat with local excision and follow up only if (a) age 40+, (b) pedunculated polyp, (c) complete excision, (d) negative mucosal margin, and (e) no inflammatory polyposis in remainder of colon
Followup: negative for dysplasia - regular surveillance (annual colonoscopy after 7-10 years of disease)
indefinite for dysplasia - more frequent follow up and treatment of active colitis
low grade dysplasia - short term follow up, more frequent if suspicious lesions
high grade dysplasia - follow up needed even after colectomy
Gross: mucosa may be flat, villous or nodular
Gross images: dysplasia in ulcerative colitis
Micro:
Low grade dysplasia: basally oriented nuclei; mild nuclear enlargement, nuclear crowding and hyperchromasia; decreased intracellular mucin
High grade dysplasia: prominent nuclear stratification (compared to low grade) with many nuclei in luminal half of cell; more significant hyperchromasia and pleomorphism; may have marked architectural distortion with a villous or nodular growth pattern resembling adenoma or with cribriforming
Indefinite for dysplasia: epithelial changes in a background of active inflammation with regeneration
Micro images: low grade dysplasia #1; #2; #3; high grade dysplasia #1; #2; #3; #4; #5; #6; #7; #8-high grade dysplasia on right side compared to reparative change on left side; #9-cytology; dysplasia (unspecified) and normal glands; low grade dysplasia or indefinite for dysplasia
regenerative change (for comparison): dispersed chromatin, prominent nucleoli and intraepithelial neutrophils-#1; #2; low grade dysplastic crypts
DD: adenoma (occurs in background of normal mucosa, no inflamed mucosa; has typical features of adenoma), reactive epithelial changes (regular nuclear contours, prominent nucleoli, adjacent cryptitis and crypt abscesses, no hyperchromasia, no pleomorphism, no nuclear stratification, no loss of nuclear polarity, no marked architectural distortions)
References: Hum Path 2000;31:288 (comparison with adenoma), J Clin Pathol 1985;38:30 (in ulcerative colitis), USCAP 2002
Ulcerative colitis
Affects 4-12 per 100,000 in US, usually whites, peak onset ages 20-25 and 70-80 years; no gender preference
Symptoms: relapsing, bloody mucoid diarrhea (stringy mucus) with pain/cramps relieved by defecation; lasts days/months, then remission for months/years; initial attack may cause medical emergency for fluid and electrolyte imbalance
60% have mild disease; 97% have one relapse per 10 year period
30% require colectomy during first 3 years due to uncontrollable disease
Almost always rectal involvement at disease onset, but may develop rectal sparing and patchiness after treatment or chronic disease, resembling Crohn’s colitis (AJCP 2004;122:94)
Moderate to markedly active chronic cecal involvement is associated with backwash ileitis (AJCP 2006;126:1, AJSP 2005;29:1472)
Associated with increased fatty acid synthase expression in both normal and diseased bowel, suggesting that disease extension is greater than normally thought (AJCP 2006;126:113)
Extraintestinal manifestations: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, pyoderma gangrenosum, clubbing of fingertips, primary sclerosing cholangitis, pericholangitis, uveitis, cholangiocarcinoma (rare)
Complications: perforation, toxic megacolon (due to toxic damage to muscularis propria and neural plexus with shutdown of neuromuscular function), iliac vein thrombosis, carcinoma, lymphoma
Skip areas: typically associated with Crohn’s disease, but occur in UC with long term oral or topical therapy; also associated with focal, appendiceal or only left sided disease; initial presentation in pediatric patients may show skip areas
Definitive diagnosis (per Sternberg): diffuse disease limited to colon, rectal involvement with continuous proximal involvement; no skip lesions; no deep fissural ulcers; no transmural sinus tracts, no transmural lymphoid aggregates or granulomas
Case reports: giant inflammatory polyposis causing obstruction (J Gastroenterol 2005;40:536)
Treatment: local or systemic steroids, infliximab (monoclonal antibody to tumor necrosis factor, N Engl J Med 2005;353:2462), total colectomy; note - steroid refractory disease is CMV+ in 25%, often detectable only by immunohistochemistry (AJSP 2004;28:365)
Gross: ulceroinflammatory disease, usually limited to colon, diffuse continuous disease from rectum proximally (pancolitis in some cases), see exceptions above; ileitis and involvement of appendix also occurs in continuity with severe colitis; anal lesions also (fissures, fistulas, skin excoriation, abscess); disease worse distally than proximally; usually no deep fissuring ulceration, no strictures or fistulas, no sinus tract formation, no small intestinal involvement, no serositis, no bowel wall thickening, no fat wrapping
Early - mucosa is hemorrhagic, granular, friable; changes usually diffuse (similar intensity throughout)
Late - extensive ulceration along bowel axis but usually not serpentine as in Crohn’s; have pseudopolyps (isolated islands of regenerating mucosa) and flat mucosa; usually normal wall thickness and normal serosa; severe cases may have megacolon or fibrotic, narrow or shortened colon
Gross images: inflammatory pseudopolyps #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; pyoderma gangrenosum (foot); continuous hemorrhage #1; #2; toxic megacolon #1; #2; active disease #1; #2
Ulcerative colitis of colon - continued
Micro: affects primarily mucosa and submucosa, except in most severe cases
Active changes include diffuse mononuclear inflammatory infiltrate in lamina propria, crypt abscesses (neutrophils in glandular lumen) and cryptitis but usually no neutrophils in lamina propria and reduced intraepithelial mucin; plasma cells are common at base of crypts (basal plasmacytosis), muscularis mucosa may be exposed by ulceration or be covered by granulation tissue and reepithelialization; submucosal fibrosis present
Chronic changes include architectural glandular disarray (branching and irregular glands, not parallel and not evenly spaced, irregular luminal border; also present in recently diagnosed ulcerative colitis) with reactive epithelial changes (nuclear enlargement, mitotic activity, reduced mucin), glandular atrophy (glands don’t reach muscularis mucosa), hypertrophic muscularis mucosa, mast cells at border with normal mucosa, Paneth cells, hyperplastic endocrine cells, mucosal capillary thrombi; pseudopolyps are composed of granulation tissue, inflamed and hyperemic mucosa, may have multinucleated stromal giant cells (J Clin Pathol 1993;46:874)
Endarteritis obliterans in submucosal arteries (10%)
No granulomas, no fissures, no transmural inflammation (except in fulminant cases), no submucosal edema or inflammation, no neuronal hyperplasia
Definitive diagnostic criteria: diffuse disease limited to colon, involvement of rectum, no transmural lymphoid aggregates or granulomas
Chronic ulcerative colitis in remission: architectural glandular disarray (branching and irregular glands, not parallel, not evenly spaced, irregular luminal border) with reactive epithelial changes (nuclear enlargement, mitotic activity, reduced mucin), glandular atrophy (glands don’t reach muscularis mucosa, reduced number of crypts), hypertrophic muscularis mucosa, Paneth cells; these findings are not specific, must be interpreted with clinical and endoscopic findings
Children: initial rectal biopsies show diffuse architectural abnormalities in fewer (32%) cases, have shorter duration of symptoms (mean 17 weeks) than adults (mean 55 weeks, AJSP 2002;26:1441)
Stomas/pouches: may develop colonic metaplasia and ulcerative colitis-like lesions, including inflammatory polyps
Micro images: inflammation limited to mucosa and submucosa; ulcer; intense inflammation with loss of goblet cells; crypt abscesses #1; #2; #3; #4 and glandular branching; #5; #6; #7; pseudopolyps #1; #2; #3; multinucleated stromal giant cells (arrows); fulminant disease; before and after treatment; backwash ileitis
Virtual slides: ulcerative colitis #1; #2 with carcinoma
DD: Crohn’s disease of colorectum (often strictures, fistulas and fissures; longitudinal and transverse ulcers, colitis more focal than diffuse, epithelium has straight colonic crypts with cytoplasmic mucin and lymphoid aggregates but no crypt abscesses and minimal mucosal atrophy; inflammation primarily involves submucosa with marked edema, submucosal nonnecrotizing granulomas in 60%, often adjacent to vessels; usually poor response to steroids), indeterminate colitis, normal rectal mucosa (normally some crypt shortening and loss of parallelism but no active colitis), acute self-limited colitis (neutrophils are present in lamina propria but no crypt distortion and no basal plasmacytosis), diverticular disease (rectal sparing, colitis only present in areas of diverticula), eosinophilic colitis (Turk J Gastroenterol 2006;17:53)
References: Mod Path 2003;16:347, Wikipedia, eMedicine #1, #2
Pediatric ulcerative colitis
More likely than adults to have patchiness of microscopic chronicity (21%), relative or absolute (23%/3%) rectal sparing, relatively normal rectal biopsies; more likely to have initial pancolitis (42%, AJSP 2004;28:190)
Ulcerative colitis associated carcinoma
Regular colonoscopy with biopsy recommended in patients with long-standing extensive colitis to detect precancerous dysplastic changes
Overall risk of carcinoma is 3-5% at 20 years, 8% at 30 years and 11% at 40 years (Gastroenterology 2006;130:1030, Inflamm Bowel Dis 2006;12:205)
10-20% have multiple tumors (more common in younger individuals)
Usually arises from flat mucosa
Tumors more often are poorly differentiated or mucinous carcinomas, also neuroendocrine neoplasms
Tumors more often are inoperable or high stage
Adverse prognostic factors for development of carcinoma in ulcerative colitis: onset in children (43% risk after 35 years), duration greater than 10 years, involvement of entire length of colon, high grade dysplastic changes, dysplasia-associated lesions and masses (DALM), pericholangitis, primary sclerosing cholangitis (Gastrointest Endosc 2002;56:48), history of pseudopolyps, family history (Br J Surg 2005;92:928)
Favorable prognostic factors: 1 or 2 surveillance colonoscopies, smoking, use of corticosteroids, aspirin or NSAIDs (Gastroenterology 2006;130:1941)
Gross (carcinomas): early - thickened mucosa with finely nodular or velvety surface
Positive stains: CK7 (usually, Virchows Arch 2006;448:756)
Carcinoma in pouches
Rare (Colorectal Dis 2004;6:494)
Primary sclerosing cholangitis may be a risk factor (Dis Colon Rectum 2003;46:770)
Case reports: developing in ileal pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (Int J Colorectal Dis 2006;21:478)
Ulcerative proctitis
Proctitis: inflammation of rectum, diagnosed by endoscopy
Ulcerative proctitis: localized form of ulcerative colitis that usually presents as fresh rectal bleeding
Good prognosis
Treatment: topical or oral aminosalicylates, steroids; most respond dramatically, 10% progress to pancolitis (Am J Gastroenterol 2000;95:469)
Gross: resembles extensive ulcerative colitis
Gross images: ulcerative proctitis #1; #2; #3
Micro: resembles ulcerative colitis, but may have mucosal lymphoid follicles
DD: lymphoid follicular proctitis (no ulceration, no acute inflammation)
Diffuse giant inflammatory polyposis of colon
Associated with inflammatory bowel disease, but rare
Clinically resembles malignancy
Benign; may be due to exuberant postinflammatory regeneration
Case reports: patient with no prior history of inflammatory bowel disease (Archives 2004;128:1286), 18 year old with chronic ulcerative proctocolitis (Cesk Patol 1998;34:63), causing colonic obstruction in ulcerative colitis (J Gastroenterol 2005;40:536), associated with Crohn’s disease (Pathol Int 2002;52:318), associated with cystic fibrosis (Pediatr Dev Pathol 2006;9:25)
Micro: villous-like polyps with irregular projections lined by hyperplastic mucosa containing numerous giant cells; marked acute inflammation; also cystically dilated glands, mucosal erosion, smooth muscle thickening; smaller polyps contain mucosa only
Gross/micro images: various images
DD: polypoid colonic carcinoma
Colitis (non-infectious)
Pathologists' role is to document presence, severity, location and extent of colitis; identify type of colitis; identify premalignant and malignant conditions and identify mimics and other colorectal disorders
Two or three levels of biopsied material is recommended
Diarrhea/dysentery-general
Normal intestines receive 9 liters of fluid per day (oral intake: 2 L, saliva: 1L, gastric juices: 2L, pancreatic juices: 2L, intestinal juices: 1L); most is reabsorbed in small intestine and colon
Diarrhea: increase in stool mass or fluidity or frequency of defecation
Secretory diarrhea: >500 ml of fluid stool per day, isotonic with plasma, persists during fasting
Dysentery: low volume, painful, bloody diarrhea
Causes of diarrhea in general:
Infectious (viral damage to epithelium): rotavirus, Norwalk virus, enteric adenoviruses
Infectious (enterotoxin): Vibrio cholera, E. coli, Bacillus cereus, Clostridium perfringens
Neoplasm: tumor production of peptides, villous adenoma in distal colon
Excessive laxatives
Causes of specific types of diarrhea:
Osmotic diarrhea: (due to luminal solutes, abates with fasting, stool osmolality > electrolyte concentration by 50 mOsm): lactase deficiency, lactulose therapy, gut lavage, antacids, primary bile acid malabsorption
Exudative disease: (purulent bloody stools, persist with fasting): bacteria (Salmonella, Shigella, Campylobacter), Entamoeba histolytica, idiopathic inflammatory bowel disease, typhlitis (neutropenic colitis in immunosuppressed)
Malabsorption: (bulky stools, abates with fasting): defective intraluminal digestion, primary mucosal cell abnormalities, reduced small intestinal surface area, lymphatic obstruction, Giardia lamblia
Deranged motility: (improper gut neuromuscular function): surgical resection of gut (decreased transit time), irritable bowel syndrome (neural dysfunction), hyperthyroidism, diabetic neuropathy, carcinoid syndrome; small intestine diverticula (decreased motility), blind loop, bacterial overgrowth
References: Wikipedia (diarrhea), Wikipedia (dysentery), eMedicine
Active colitis
A non specific diagnosis that encompasses identifiable bacterial infections, infectious (acute self-limited) colitis, and non-infectious active colitis (focal or diffuse)
Focal active colitis: patchy architectural changes and inflammation; suggestive of Crohn’s colitis or acute self limited/infectious colitis; may also include some cases of treated ulcerative colitis, ischemia, NSAID related colitis and bowel preparation changes; does NOT encompass chronic colitis with only focal acute inflammation
Diffuse active colitis: somewhat specific for active phase of ulcerative colitis, although also present in some cases of Crohn's colitis, infectious colitis and diverticular disease
Micro: neutrophils present in lamina propria, within epithelial cells (cryptitis) or within crypt lumina (crypt abscess); inflammation, edema and hemorrhage of lamina propria; variable necrosis and microthrombi; often acute inflammation is more marked than associated chronic inflammation
Micro images: acute self-limited colitis; cryptitis
Allergic colitis
Occurs in infants/children related to food, particularly cow’s milk in infants and soy or eggs in older children
Some clinical cases of food allergy in young children are eventually diagnosed as inflammatory bowel disease (Med Wieku Rozwoj 2006;10:475)
Symptoms: rectal bleeding (although nonspecific, J Pediatr Gastroenterol Nutr 2005;41:16), variable diarrhea; may have peripheral eosinophilia
Case reports: premature infant with rectal bleeding after first formula feeding (Acta Paediatr 2005;94:1514)
Treatment: removal of cow’s milk from infant or (if breast fed) mother’s diet
Micro: rectal biopsy shows mucosal edema, prominent eosinophils (>60 per 10 HPF) aggregating around lymphoid nodules, in crypt abscesses and around muscularis mucosa; may have mild focal active colitis
DD: Dientamoeba fragilis infestation (J Pediatr Gastroenterol Nutr 1998;26:16)
References: J Pediatr Gastroenterol Nutr 1994;19:22.
Antibiotic associated colitis
Also called pseudomembranous colitis
Acute colitis with adherent inflammatory exudate (pseudomembrane) overlying sites of mucosal injury, usually after broad spectrum antibiotics (clindamycin, lincomycin, others), which favor the overgrowth of Clostridium difficile over other gut bacteria
Also after surgery or chronic debilitating illness without antibiotics
Increasing rates in elderly (Emerg Infect Dis 2006;12:409, Nippon Ronen Igakkai Zasshi 2002;39:271)
Recently, severe cases have been reported in low risk populations (MMWR Morb Mortal Wkly Rep 2005;54:1201, Lancet 2005;366:1079); may be associated with fluoroquinolone use (Infect Control Hosp Epidemiol 2005;26:273)
Clostridium difficile, a normal gut commensal, may produce toxin A, which causes intestinal secretion and acute inflammation
Symptoms: acute or chronic diarrhea; may cause toxic megacolon and perforation
Diagnosis: detect Clostridium difficile toxin (toxin A-enterotoxin or less commonly toxin B-cytotoxin) in stool (Am J Med 2006;119:356.e7, J Clin Microbiol 2006;44:1145)
Case reports: 74 year old man post-antibiotics for vascular surgery
Treatment: vancomycin or metronidazole; 25% may relapse; toxoid vaccine may be effective in recurrent cases (Gastroenterology 2005;128:764)
Gross: yellow-white mucosal plaques or pseudomembranes; may resemble polyps or aphthoid ulcers of Crohn’s disease
Gross images: hyperemic mucosa and green-yellow exudate #1; #2; #3; #4; #5; #6; #7; #8; #9; #10
Micro: denuded epithelium; mucopurulent exudate erupts out of crypts to form a mushroom-like cloud with a linear configuration of karyorrhectic debris and neutrophils that adheres to surface; superficial crypts show patchy necrosis and dilation; later in disease, entire crypt becomes necrotic and disease resembles ischemic colitis; adjacent mucosa is normal, although it may be covered by pseudomembrane; superficial lamina propria contains dense neutrophils and some capillary fibrin thrombi
Micro images: pseudomembrane with intact mucosa #1; #2; #3; pseudomembrane contains abundant neutrophils #1; #2; #3; #4; #5; superficial ulcer with pseudomembrane; eruption of exudate resembling mushroom cloud #1; #2; various images; mucosal ulceration with neutrophils #1; #2
Virtual slides: antibiotic associated colitis
References: Clin Microbiol Rev 2005;18:247 (mechanism of action of toxins), Merck manual, eMedicine #1, #2
Behcet’s syndrome of colon
Multisystem inflammatory disorder of unknown origin
Aphthous stomatitis, genital ulcers, relapsing iritis; also arthritis, cutaneous and vascular disease
More common in region from Mediterranean to eastern Asia
2/3 in males
GI involvement in 10% (ileum, cecum); causes pain, diarrhea, melena; rarely perforation (Surg Today 2003;33:383)
Case reports: 29 year old woman with severe colitis (AJSP 1986;10:888), with pyoderma gangrenosum which resolved after colectomy (World J Gastroenterol 2006;12:979), in monozygotic twins (J Gastroenterol 2005;40:421), resembling inflammatory bowel disease (Intern Med 2004;43:243), with longitudinal ulcers and granulomas resembling Crohn’s (J Gastroenterol Hepatol 2002;17:105)
Treatment: steroids, including intra-arterial
Gross: numerous punched out ulcers of various sizes, shapes and depths in colon
Micro: ulcers with neutrophils around ulcer bed, lymphocytic vasculitis in submucosal veins
note: diagnosis is clinical, not histologic
Micro images: various images
Micro images (all PDF files): figures 3-4: ulcer and lymphoid hyperplasia; figures 3-4: ulcers and perforations; figure 2: ulcers in ileum and colon
DD: Crohn’s colitis
References: eMedicine #1, #2
Brainerd diarrhea
Chronic watery diarrhea of unknown etiology with acute onset and long duration
First case in 1983 in Brainerd, Minnesota (USA)
Similar to epidemic infectious diarrhea, but symptoms usually last 4+ weeks, often years
Most patients recover within 3 years or less
Case reports (outbreaks): California restaurant (Clin Infect Dis 2006;43:62), Texas restaurant (Clin Infect Dis 2006;43:55), cruise ship (J Infect Dis 1998;177:1041)
Micro: surface epithelial lymphocytosis (similar to lymphocytic colitis) without architectural distortion, degenerative changes or thickened subepithelial collagen
References: AJSP 1996;20:1102, Centers for Disease Control
Collagenous colitis
History of chronic watery diarrhea and crampy abdominal pain with normal colonoscopy and barium enema
Mucosal splitting after endoscopic insufflation is specific but rare (J Clin Gastroenterol 2004;38:341, Scand J Gastroenterol 2006;41:726), may cause colonic perforation (Eur J Gastroenterol Hepatol 2005;17:121)
85% in elderly women, often smokers
Most cases in Western countries, rare in Asia or Africa
Associated with autoimmune disease (celiac sprue, J Clin Pathol 1992;45:784, J Clin Gastroenterol 2004;38:664), myasthenia gravis, thyroiditis, rheumatoid arthritis, autoimmune gastritis
May be associated with lansoprazole (Z Gastroenterol 2005;43:657); ulceration is associated with NSAIDs (Am J Gastroenterol 2003;98:1834)
May represent similar disease entity as lymphocytic colitis
May precede diagnosis of Crohn’s disease (Eur J Gastroenterol Hepatol 2005;17:573)
Case report: 56 year old man with diarrhea (grand rounds)
Treatment: sulfasalazine, budenoside (Aliment Pharmacol Ther 2005;22:1115), high dose bismuth
Micro: patchy thickening of subepithelial basement membrane of 10 microns or more (thickest in transverse colon); often spares the rectosigmoid; lower border of collagen is irregular and extends into lamina propria and encircles capillaries; also increased chronic inflammatory cells (lymphocytes, plasma cells, eosinophils) in lamina propria and within surface epithelium (20+ lymphocytes per 100 epithelial cells); epithelial damage is evident by loss of mucin and irregular orientation of nuclei; usually no neutrophilic infiltration, no atrophy, no mucosal architectural distortion; 6+ intraepithelial lymphocytes per 100 epithelial cells in terminal ileum is 98% specific and 50-60% sensitive for collagenous/lymphocytic colitis (AJSP 2002;26:1484);
Micro images: H&E and trichrome; increased subepithelial collagen #1; #2; #3; #4; #5; #6-increased subepithelial collagen #1; #7 with endoscopic images; #8-patient with lymphocytic colitis (A) and collagenous colitis (B); trichrome #1; #2; #3; #4; #5; various images #1; #2
Positive stains: trichrome (recommended, rules out amyloid deposition)
DD: nonspecific changes, tangential sectioning of
subepithelial basement membrane (lacks inflammation), lymphocytic colitis (no
collagen), scleroderma (affects muscularis propria), chronic ischemic damage
(fibrosis in lamina propria), solitary rectal ulcer syndrome (mucosal
architectural distortion, variable collagen deposits but no intraepithelial
lymphocytes)
References: eMedicine
Diversion colitis
Also called defunctionalized bowel
Due to dietary deprivation of short-chain fatty acids normally produced by colonic bacteria, which are important for caloric supply of colonic enterocytes
Similar histologic features regardless of cause for diversion, although patients with IBD may have superimposed IBD histologic changes
Diagnosis can only be made with confidence if colon was non-inflamed at time of surgical diversion
In children, resembles normal appendix (Histopathology 2000;36:41, Hum Path 1993;24:211)
Causes: ileostomy, colostomy, other surgical diversion
Symptoms: varies from none to severe diarrhea resembling ulcerative colitis
Treatment: enemas, dietary short term fatty acids, restoring continuity of segment (Curr Treat Options Gastroenterol 2001;4:255)
Gross: variable from minimal mucosal friability to ulceration
Micro: marked lymphoid hyperplasia resembling follicular proctitis or aphthous lesions, initially in lamina propria but later transmural, mild colitis with crypt abscesses; late in disease develop muscularis mucosa hypertrophy, fatty and fibrous infiltration of submucosa, thickened muscularis propria and narrow lumen; no architectural distortion
Micro images: lymphoid hyperplasia; diversion proctitis with diffuse chronic inflammation of lamina propria and crypt abscesses but no architectural distortion
DD: Clostridium difficile infection (Dis Colon Rectum 2006;49:1074)
References: AJSP 1990;14:548, Hum Pathol 1990;21:429
Diverticular colitis
Also called segmental colitis associated with diverticula
Colitis related to diverticular disease
Affects sigmoid colon only with rectal sparing
Usually presents with rectal bleeding
Good prognosis (Endoscopy 2006;38:610); does not appear to evolve to inflammatory bowel disease (Int J Colorectal Dis 2005;20:28)
Case report: 54 year old man with hematochezia
Treatment: high fiber diet, antibiotics, aminosalicylates; surgery may be necessary (Colorectal Dis 2001;3:149)
Micro: transmural inflammation with expansion of lamina propria, cryptitis and crypt abscesses, lymphoid aggregates and distorted crypt architecture
Micro images: various images
DD: inflammatory bowel disease and acute self-limited colitis (have different clinical history)
References: AJSP 1996;20:94, Pathology 2002;34:568, Colorectal Dis 2002;4:208, Am J Gastroenterol 1992;87:609
Eosinophilic colitis / proctitis
Causes include eosinophilic gastroenteritis (peripheral eosinophilia, allergic history), allergic proctitis in adults (resembles ulcerative colitis), allergic colitis (see above), Anasakis (AJSP 2003;27:1167), Strongyloides (Ital J Gastroenterol Hepatol 1999;31:607) or other parasites, clozapine (Ann Clin Psychiatry 1995;7:97) and carbamazepine (Epilepsia 1992;33:119)
Case reports: with ascites (Saudi Med J 2005;26:1983), with bone marrow transplantation (Int J Hematol 2003;78:76), with Enterobius vermicularis (Ned Tijdschr Geneeskd 2003;147:813)
Micro: large numbers of eosinophils
Micro images: eosinophilic colitis #1; #2; #3; #4
DD: early ulcerative colitis (Turk J Gastroenterol 2006;17:53)
Graft versus host disease of colon
Acute GVHD is defined as symptoms (abrupt onset of severe, watery diarrhea) and histologic evidence within 100 days of transplant or donor lymphocyte infusion
Chronic GVHD rarely affects colon and causes submucosal fibrosis, mucosal calcification, focal fibrosis of lamina propria; may also have architectural glandular distortion similar to inflammatory bowel disease (Mod Pathol 1998;11:513)
Acute GVHD grading: 1 - apoptosis (collection of eosinophilic globules and nuclear debris); 2 - apoptosis and crypt abscesses; 3 - total necrosis of individual crypts; 4 - total denudation of areas of bowel
Distal colon is optimal biopsy site (Bone Marrow Transplant 2006;38:371)
Case reports: GVHD limited to bowel after transplant for CML (Hematology 2004;9:131), pediatric liver transplant patients with late disease (Pediatr Transplant 1999;3:236)
Gross images: hemorrhagic mucosa #1; #2
Micro: focal crypt cell necrosis/apoptosis (intracryptal apoptosis is specific, BMC Gastroenterol 2003;3:5), minimal inflammation; when severe, see sloughing of mucosa, sepsis, hemorrhage; may form inflammatory polyps; often sparing of endocrine cells (J Clin Pathol;44:86)
Micro images: apoptotic bodies in crypts #1; #2; #3; #4 (grade III); #5a (grade IV); #5b; focal crypt abnormalities; various images
DD: CMV colitis, EBV associated post-transplant lymphoproliferative disorder (Pediatr Transplant 2000;4:151), chemotherapy or radiation related changes (usually resolve after 7-20 days), AIDS related changes
References: Curr Opin Gastroenterol 2005;21:64, eMedicine
Causes: Crohn’s disease, tuberculosis, Yersinia
Case reports: due to Propionibacterium acnes, a low virulence skin bacteria (Archives 2001;125:1491)
Micro images (P. acnes): image1, image2; cause unknown
DD: germinal centers, tangential sections of blood vessels or pericryptal fibroblastic sheath, inflammatory reaction to extravasated mucin, rarely sarcoidosis (Am J Gastroenterol 1998;93:1949)
Abdominal cramping, bloody diarrhea, low grade or no fever
Usually resolves spontaneously, but may be complicated by hemolytic uremic syndrome or thrombotic thrombocytopenic purpura
Endoscopy: right sided colonic edema, erosions, hemorrhage
Causes: E. coli O157:H7 from undercooked hamburger, unpasteurized gouda cheese (Can J Public Health 2005;96:182); also alfalfa spouts, unpasteurized fruit juice, dry-cured salami, lettuce, game meat, raw milk
Micro: hemorrhage and edema in lamina propria; focal superficial mucosal necrosis with preservation of deeper portion of crypts; acute inflammation; may have inflammatory pseudomembranes
References: Adv Intern Med 1992;37:173, US Food and Drug Administration
Ischemic colitis
Usually age 50+ years
Causes: bowel obstruction, diabetes, drugs (Kayexalate [see below], NSAIDs, potassium chloride pills), hypercoagulable states (South Med J 2004;97:120), intestinal Behcet’s disease, pseudomembranous colitis, radiation, stress ulcer, surgery, vascular disease (atherosclerosis, dissecting aneurysms, small vessel vasculitis, thromboemboli), uremia
Intestinal ischemia occurs in 3% of renal transplant patients (Archives 2002;126:1201)
In younger patients, associated with amyloidosis, birth control pills (AJSP 1995;19:454), cocaine (South Med J 2000;93:909), collagen vascular disease, hypovolemia or marathon running (J Emerg Med 2006;30:321), phlebitis, thromboemboli, vasoactive drugs, Wegener’s granulomatosis; often is idiopathic (J Gastrointest Surg 2001;5:388)
Occurs in infants with necrotizing enterocolitis
Note: loss of one major colonic vessel may not cause symptoms due to rich anastomotic interconnections; however lesions of end arteries causes small, focal ischemic lesions
Splenic flexure and rectum are prone to ischemia because they have less blood supply
Ischemic changes may be mucosal, mural (hypoperfusion) or transmural (major vessels involved)
Note: chronic ischemia may produce similar changes as acute ischemia, may be segmental and patchy
Symptoms: sudden onset of abdominal pain and bleeding
Complications: intestinal gangrene in 1-4 days, bacterial superinfection, enterotoxin formation (pseudomembranes), stricture; perforation may be fatal
Case reports: due to phlebitis (Mod Path 2000;13:897)
Treatment: excise ischemic regions if perforation, peritonitis or transmural infarction
Grossing specimens: carefully dissect blood vessels and submit many sections to detect vascular lesions
Gross: ulceration (may be discrete or serpiginous) with possible cobblestone pattern resembling Crohn’s disease or pseudopolyps resembling ulcerative colitis; appears hemorrhagic due to blood reflow; frank blood or dark mucus in lumen; segmental thinning in areas of full-thickness infarction or gangrene; late fibrosis and stricture formation
Gross images: splenic flexure and upper rectum; superficial hemorrhage; with ulceration #1; #2; #3; with pseudopolyps
Micro: necrosis, ulceration and granulation tissue extending into submucosa and surrounding smooth muscle fibers of muscularis mucosa; hemosiderin / hemorrhage and edema in lamina propria; hyaline thrombi in small vessels; may see crypt abscesses; deep portion of colonic crypt is often spared; usually are few inflammatory cells; suggestive features are surface exudate of neutrophils and fibrin or mucosal necrosis (early) or transmural fibrosis (late); endoscopically normal mucosa has no microscopic abnormalities
Micro images: superficial ulceration #1; #2; #3; #4; #5 with hyaline thrombi; damaged epithelium #1; #2; #3; #4; regenerating crypts; granulation tissue; renal transplant associated-figures 5-7; atherosclerotic emboli
Virtual slides: hemorrhagic infarct; ischemic colitis
DD: Crohn's disease (younger patients, transmural inflammation, no necrosis), ulcerative colitis (cryptitis and crypt abscesses, basal plasmacytosis, no fibrosis of muscularis propria, no hemosiderin deposition), E. coli O157:H7 infection (occurs in epidemiological clusters, younger patients, right sided)
References: South Med J 2005;98:217 (clinical review), eMedicine
Kayexalate (sodium polystyrene) is an ion-exchange resin administered via nasogastric tube or enema to treat hyperkalemia by binding intraluminal potassium, which is then excreted
Since it also binds calcium and may cause constipation, it is given with sorbitol, which acts as laxative
Kayexalate with sorbitol may cause ischemia and intestinal necrosis
Diagnosis requires identification of Kayexalate crystals, although the hyperosmolar sorbitol may actual cause the disorder (South Med J 2000;93:511, J Perinatol 1995;15:139)
Case reports: two cases; association with uremia (Can J Gastroenterol 1997;11:573)
Micro: basophilic crystals with fish-scale appearance on H&E; refractile but not polarizable
Micro images: Kayexalate associated colitis; incidental luminal polystyrene sulphonate resin particles in jejunal diverticular tissue; particles at site of colonic necrosis (Direct Schiff stain with light counterstain); particles at site of aspiration pneumonia (Ziehl-Neelsen stain with light counterstain)
Positive stains: acid-fast (red)
DD: cholestyramine crystals (rhomboid and opaque on H&E, pink with acid-fast stain)
References: Surgery 1987;101:267, AJSP 1997;21:60
Lymphocytic colitis
“Microscopic colitis” now describes both collagenous colitis and lymphocytic colitis
Chronic, nonbloody, water diarrhea, with normal endoscopy in middle aged patients
Reported gender predilection varies from equal to female predominance
Associated with autoimmune diseases (autoimmune gastritis, celiac sprue [J Clin Gastroenterol 2001;32:225], myasthenia gravis, rheumatoid arthritis, thyroiditis), and a family history of bowel disorders in Sweden (Gut 2004;53:536)
May represent similar disease entity as collagenous colitis
Confirm presence of chronic diarrhea before making diagnosis
Recent study suggests associated with E coli (World J Gastroenterol 2005;11:7266), and is seasonal (J Clin Gastroenterol 2005;39:891)
Case reports: associated with autoimmune hepatitis (J Clin Gastroenterol 2006;40:648)
Treatment: sulfasalazine, corticosteroids
Micro: colonic epithelial lymphocytosis (15-20+ per 100 epithelial cells) with surface epithelial damage but without thickened subepithelial collagen; also crypt distortion and increased chronic inflammatory cells in lamina propria; in terminal ileum, 6+ intraepithelial lymphocytes per 100 epithelial cells is 98% specific and 50-60% sensitive for collagenous/lymphocytic colitis (AJSP 2002;26:1484)
Micro images: intraepithelial lymphocytes #1; #2; #3; #4; #5; comparison with collagenous colitis #1; #2-A: lymphocytic colitis; B: collagenous colitis
DD: bowel preparation changes, drug reaction, Hashimoto’s thyroiditis, Brainerd diarrhea, inflammatory bowel disease
References: eMedicine
Paucicellular variant
Similar to classic variant, but may not have watery diarrhea (AJCP 2004;122:405)
Caution: only one report on this entity through August 2006
Micro: increased intraepithelial lymphocytes separated by normal mucosa; mildly increased lymphoplasmacytic infiltrate in lamina propria
Micro images: various images
Uncommon inflammatory condition confined to rectum
Rectal bleeding and discontinuous endoscopic mucosal changes confined to rectum
Does not progress to ulcerative proctitis or lymphoma
Treatment: mesalazine suppositories (Korean J Gastroenterol 2006;47:420)
Micro: dense lymphoid infiltrate and follicular hyperplasia of mucosa with congestion; no ulceration; no neutrophils
Micro images: dense lymphoid infiltrates before treatment (page 423)
References: Dig Dis Sci 1988;33:314
Malakoplakia of colon
May diffusely involve colon
Usually adults, associated with immunosuppression
Present in rectum in elderly males with colorectal carcinoma (Pathology 2002;34:332)
Due to defective inflammatory response to gram negative bacterial infection
Case reports: with liver transplant (Archives 2004;128:e133), adjacent to adenocarcinoma (J Clin Pathol 1993;46:959), 4 year old boy with celiac disease and chronic granulomatous disease (Indian J Gastroenterol 2006;25:163)
Gross: diffuse mucosal involvement and submucosal thickening; may cause mass
Micro: marked histiocytic infiltrate containing Michaelis-Gutmann bodies (calcospherites) that may resemble signet ring cells at frozen section
Micro images: Michaelis-Gutmann bodies #1 (arrows); #2; #3; figures 1/2: H&E; 3: PAS; 4: calcium; adjacent to adenocarcinoma
Chronic intractable diarrhea (liquid/loose stools for more than 4 weeks)
Symptoms usually controlled by drugs affecting mast cell mediator function and release (Archives 2006;130:362)
A diagnosis of exclusion
Note: only one major study about this disorder
Micro: defined as more than 20 mast cells per high power field and no other significant histologic findings
Micro images: mast cells in normal colon are tryptase+ (figure 4a); increased mast cells (figure 5a)
Positive stains: tryptase
DD: ulcerative colitis with mast cells
Necrotizing enterocolitis
Acute, necrotizing inflammation of small intestine or colon
Common at 2-4 days of life in premature or low birth weight neonates
May be associated with Hirschsprung’s disease, thrombosis of abdominal aorta, H2 blockers (Pediatrics 2006;117:e137) or chemotherapy for hematopoietic malignancies (Int J Hematol 2005;82:319)
Symptoms: abdominal distention, loss of bowel sounds, blood-stained stool
Complications: bowel perforation, short bowel syndrome, malabsorption (due to ileal resection), strictures, recurrence
Causes: oral feeding of neonates with immature gut immune system causes release of proinflammatory cytokines; bacteria in food produce more cytokines which injure mucosa; intestinal blood flow may be disturbed
Affects terminal ileum and ascending colon
Treatment: fluids and surgery if gangrene/perforation
Gross: necrotic mucosa, submucosal gas-filled cysts
Gross images: in situ; thickened wall with areas of necrosis and constriction; non-continuous disease in newborn; focal dusky cyanosis #1; #2; thickened wall, mucosal ulceration and cyst-like spaces; transverse section shows cyst-like spaces in wall
Micro: early - mucosal edema, hemorrhage, necrosis, pneumatosis cystoides intestinalis; late - hemorrhagic and gangrenous bowel wall with strictures if patient survives
Micro images: hemorrhagic necrosis; mucosal necrosis and cyst-like spaces in submucosa; submucosal cyst-like spaces #1; #2 lined by flattened cells; subserosal lymph node with cyst-like spaces; various images
References: J Clin Pathol 1979;32:1090, Northwestern University (Illinois, USA), eMedicine #1, #2
Causes bleeding, diarrhea or abdominal pain
Endoscopy: small erosions in different parts of colon
Treatment: discontinuation of NSAIDs (Z Gastroenterol 2000;38:957)
Micro: usually mixed inflammatory infiltrate, may also be predominantly neutrophilic or lymphocytic; often erosions, crypt architectural disarray; no granulomas
Micro images: ulcer post-NSAID therapy; erosion and neutrophils
DD: Crohn’s colitis, focal active colitis, ischemic colitis
References: AJCP 1998;110:622, Pathologe 2006;27:65, Adv Anat Pathol 1999;6:213
Pouch related complications in colon
Ileal pouches are formed from loops of terminal ileum, may be anastomosed to rectum to preserve anal sphincter function and restore continuity of bowel
Contraindicated in Crohn’s disease due to high risk of fistula and abscess
Complications: fistula, obstruction, incontinence, anastomotic leaks; 2-7% of cases are due to initially undiagnosed Crohn’s disease
Micro (normal pouch): resembles terminal ileum, occasional superficial neutrophils, mild villous shortening, increased chronic inflammation
Pouchitis
Inflammation of ileal reservoir mucosa
Late complication that occurs in 8-46%, no strict case definition exists
Nausea, vomiting, malaise, fever, abdominal pain; increased watery, foul smelling or bloody stool; often incontinence
Associated with appendiceal ulceration (41% of pouchitis patients vs. 0% of controls, AJSP 2004;28:999)
May be due to altered flora of microorganisms
May represent 6 different conditions according to Sternberg:
Classic pouchitis - pouch appears to be source of clinical symptoms; responds to antibiotics
Proximal jejunal bacterial overgrowth - secondary to pouch distention that decreases intestinal motility; also responds to antibiotics
Irritable pouch syndrome - severe clinical symptoms, but normal histology and endoscopy; may respond to fiber supplements and antidepressants
Short-strip pouchitis - may be due to exacerbation of ulcerative colitis in retained rectal segments of surgical anastomoses; responds to corticosteroids
Crohn’s disease - may present as late pouch fistula or pouchitis with granulomas
Primary refractory pouchitis - excision of pouch shows no Crohn’s disease; cause unknown, but may be related to stasis, bacterial overgrowth, IBD related immune alterations or colonic type metaplasia; may develop dysplasia secondary to colonic-type metaplasia
Pouchitis with dysplasia - associated with refractory pouchitis and colonic type metaplasia (type C below)
Endoscopy images: various images
Treatment: initially antibiotics or possibly probiotics (Gut 2006;55:833); later steroids, sulfasalazine or pouch excision if necessary; follow patient to rule out dysplasia
Micro: ulcers with granulation tissue, cryptitis, crypt abscesses, patchy neutrophils in lamina propria, decreased epithelial cell mucin, decreased/no lymphoid follicles
Micro images: pouchitis
Type A pouch mucosa (~60%): normal small bowel histology, no/mild mucosal atrophy, no/minimal inflammation
Type B pouch mucosa (~40%): transient atrophy and moderate/severe inflammation, then normalization of mucosa
Type C pouch mucosa (~10%): permanent persistent atrophy and severe inflammation; well developed but still incomplete colonic-type metaplasia
Radiation enterocolitis
Acute or chronic
May be side effect of radiation therapy for cervical, prostate or rectal carcinoma
Endoscopy images: various images
References: eMedicine
Acute radiation enterocolitis
Anorexia, cramps, malabsorptive diarrhea due to mucosal injury; usually subsides after 1-2 months with no complications
Micro: may have bizarre cellular changes in crypt epithelium, fibroblasts and endothelium; also crypt abscesses, numerous eosinophils, apoptotic bodies; severe cases may include ulceration, necrosis, hemorrhage, perforation; architecture is preserved, low N/C ratio, no/minimal mitotic activity
DD: carcinoma (loss of architecture, no “bizarre” atypia, high N/C ratio, mitotic activity, infiltrative, desmoplastic stroma), infectious colitis, collagenous colitis, ischemic colitis, NSAID colitis, inflammatory bowel disease
References: AJSP 2002;26:498
Chronic radiation enterocolitis
May present as inflammatory colitis
Treatment: possibly female hormonal therapy (Am J Gastroenterol 1998;93:2536)
Gross images: image1
Micro: atrophic mucosa, ectatic vessels in lamina propria, vascular injury (intimal fibroplasia, foamy macrophages and hyaline within vessel walls), ischemic fibrosis, stricture
Case report: history of talc tablets for treating pulmonary tuberculosis 18 years prior (AJSP 1987;11:890)
Micro: prominent fibrosis of intestinal wall with birefringent particles by polarized light
Typhlitis of colon
Also called hemorrhagic necrosis of bowel wall, neutropenic colitis
Often in leukemia or lymphoma patients after immunosuppressive therapy
Typhlitis is a 19th century term for severe acute/chronic inflammation of the cecum/appendix, probably due to untreated acute appendicitis; now it represents a life threatening acute inflammatory destruction of cecal mucosa in neutropenic patients, possibly due to impaired mucosal immunity and compromised blood flow; also associated with secondary bacteria and fungal overgrowth but minimal active inflammation (due to neutropenia)
May cause perforation and require surgery
Severity in childhood cancer is related to duration of neutropenia and presence of fever or abdominal tenderness (Cancer 2005;104:380)
Poor prognosis overall with death in up to 50% (Rev Esp Enferm Dig 2003;95:30)
Usually diagnosed by CT scan due to thickening of cecal wall
Gross: inflamed cecum and proximal right colon with hemorrhage and mucosal edema
Gross images: CML in blast crisis with candida infection and grossly enlarged lymphoid follicles; colonic stenosis in neutropenic patients
Micro: adherent fibrinopurulent exudate over necrotic and edematous mucosa
Micro images: colonic stenosis in neutropenic patient
References: eMedicine
Infectious colitis (specific microorganisms)
Very rare
Caused by anaerobic bacterium, Actinomyces israelii, which is normal GI flora
Abdominal pain, fever, leukocytosis, intestinal wall thickness or abdominal mass (Acta Chir Belg 2006;106:351, Cir Cir 2005;73:47)
Case reports: clinical tumor and resection (BMC Gastroenterol 2005;5:1, West Afr J Med 2005;24:343), obstruction (Scand J Infect Dis 2006;38:231, Braz J Infect Dis [online] 2004;8:186), containing a fish bone (Surg Today 2006;36:187), combined intra- and extraabdominal actinomycosis (Rom J Gastroenterol 2004;13:337)
Gross images: actinomycotic abscess
Micro images: large spherical clusters of bacteria and sulfur granules; sulfur granules and neutrophils
References: eMedicine #1; #2
Associated with HIV infection (Gastroenterology 1991;100:976) but often overlooked (J Clin Pathol 1992;45:684, AJSP 1998;22:1101)
One third of cases also have CMV infection
Micro: necrotic epithelial cells, cellular debris, amphophilic or eosinophilic intranuclear inclusion in surface epithelial cells, particularly goblet cells; inclusion completely fills nucleus, is often irregular; no cytoplasmic inclusions; also chronic inflammation and moderate architectural changes
Micro images: HIV+ patient whose infected cells have irregular amphophilic nuclei; #2-six infected cells exhibit eccentric nuclei and vacuolated cytoplasm; #3-immunostain; figures C-E
Positive stains: adenovirus immunostain
EM images: intranuclear inclusions with (inset) regular pattern of arrangement; hexagonal arrangement (site unknown)
Amebic colitis
Also called amebiasis
Clinically resembles ulcerative colitis, Crohn’s disease or appendicitis, but caused by Entamoeba histolytica protozoa
Fecal-oral spread
Causes dysentery, perforation (5%) or is nonpathogenic
Increased incidence in homosexuals, AIDS patients and patients from tropics
Usually affects cecum or ascending colon, but may involve entire colon or even terminal ileum
40% invade portal vessels, embolize to liver and cause abscesses up to 10 cm; rare abscesses in lung, heart, kidneys or brain
Case reports: causing colonic stricture (Turk J Gastroenterol 2005;16:236), causing fulminant necrotizing colitis (Surg Today 2002;32:738)
Drawings: life-cycle
Gross: discrete areas of ulceration covered by exudate with normal intervening mucosa
Gross images: ulcers #1; #2; #3
Micro: flask shaped ulcer with broad base in lamina propria; minimal inflammatory cells; trophozoites of Entamoeba histolytica (resemble macrophages) are round/oval, surrounded by a halo, 6-40 nm, contain abundant cytoplasm with distinctive vacuoles; have small, round nuclei with prominent nuclear borders and central karyosome (chromocenter, chromatin mass); may contain ingested red blood cells
Micro images: flask shaped ulcer; trophozoite #1; #2; #3; #4; #5; #6; #7; #8; PAS; low power #1; #2; medium power #1; #2; #3; amoeba in stool #1; #2; #3; immunostain
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Virtual slides: amebiasis
Positive stains: PAS
References: Clin Microbiol Rev 2000;13:318 (pathogenesis), eMedicine #1, #2
Balantidiasis of colon
Infection by the parasite Balantidium coli causing bloody diarrhea
The only ciliated parasite in man
Affects cecum and rectosigmoid
Prevalence of 1-5% in asymptomatic Aymara children in northern Bolivia (Am J Trop Med Hyg 1998;59:922)
Present in pigs in tropics and food/water contaminated by pig feces, but low prevalence in industrialized countries
Case reports: severe peritonitis in France (Eur J Clin Microbiol Infect Dis 2004;23:393), patient from Turkey with non-Hodgkin’s lymphoma (World J Gastroenterol 2004;10:458)
Diagrams: life cycle
Micro: flask shaped ulcers containing green-yellow trophozoites (60 x 35 microns)
Micro images: various images #1; #2; #3; trophozoite #1; #2 (Lugol preparation); #3; #4
EM: flattened oval organism covered with cilia with gullet at anterior end
References: eMedicine
Infection by fungus Basidiobolus ranarum
More common in skin and subcutis, rare in GI tract
Most cases are from Africa, South America and tropical Asia
May be associated with colonic perforation (AJCP 1999;112:610)
Case reports: infection in 41 year old Indian man from region where subcutaneous disease is endemic (J Clin Microbiol 2001;39:2360), cases in Arizona (USA) in 1999-99
Micro: marked mural thickening with fibrosis, prominent eosinophils, palisading granulomas around pale thin-walled but broad and often aseptate hyphae; also spore-like spherules with occasional septal hyphae surrounded by a thick eosinophilic cuff (Splendore-Hoeppli phenomenon)
Micro images: various images; arm lesion; spore forms #1; #2; #3
References: University of Adelaide
Campylobacter jejuni of colon
Most common cause of bacterial enteritis in humans
Invades colonic mucosa and causes dysentery or diarrhea with purulent exudate; also fever and abdominal pain
Due to contaminated milk, poultry, animal contact
Molecular diagnosis possible on formalin fixed tissue (AJSP 2006;30:782)
Micro: focal cryptitis with preservation of crypt architecture
Micro images: crypt abscess #1; #2; cryptitis #1; #2; acute colitis without necrosis; loss of crypts; cystic crypts and cryptitis; edema, cryptitis and crypt abscess #1; #2; marked edema causes separation of base of crypts from muscularis mucosa; neutrophilic aggregates (arrows) in lamina propria without plasma cells or lymphocytes
DD: acute inflammatory bowel disease (J R Soc Med 1985;78:217)
References: eMedicine #1, #2, J Clin Pathol 1979;32:990, University of Texas Medical Branch
May cause diarrhea although fungi are usually not invasive (Clin Infect Dis 1995;21:881)
Common cause of chronic infective diarrhea in Indonesia (Acta Med Indones 2004;36:211)
Case reports: invasive disease in AIDS patient (J Comput Assist Tomogr 1994;18:298), with acute cerebral hemorrhage due to invasive disease (J Clin Gastroenterol 2005;39:795), with hemodialysis (Eur J Gastroenterol Hepatol 2001;13:735)
Virtual slides: Candidiasis
Chagas disease (trypanosomiasis) of colon
Exists only in North, South and Central America
Caused by Trypanosoma cruzi, transmitted to humans by blood-sucking triatomine bugs, blood transfusion or organ transplant
Invades bowel wall and destroys enteric plexuses; may cause toxic megacolon (life-threatening complication of markedly dilated colon, abdominal distention and variable fever, pain or shock); may destroy interstitial cells of Cajal (Pathophysiology 2006;13:71)
Not associated with colon carcinoma (Rev Inst Med Trop Sao Paulo 2003;45:91)
Typing is possible for epidemiologic studies (Int J Parasitol 2005;35:411)
Gross images: megacolon #1; #2; #3
Micro: mast cells and fibrosis (Rev Soc Bras Med Trop 2003;36:461)
Micro images: mast cells (figure 2); not colon - blood #1; #2; heart #1; #2; #3
References: Mem Inst Oswaldo Cruz 2003;98:577, Emedicine #1, #2, University of South Carolina
Clostridium botulinum of colon
In infants, caused by honey ingestion or unknown (MMWR)
In infants, colonizes the GI tract and forms toxins; may present with constipation, later hypotonia, drooling and weak cry; 50% have upper airway obstruction and cranial palsies; may also have muscular weakness (Pediatr Neurol 2005;32:193)
May produce rapid, fatal respiratory failure
May cause some cases of sudden infant death syndrome (Lancet 1985;1(8423):237, Lancet 1978;1(8077):1273)
Diagnosis: toxin identification or culture in stool samples, electromyography (Ned Tijdschr Geneeskd 2005;149:826)
References: American Family Physician, eMedicine
CMV colitis
Associated with AIDS or transplant patients
Usually affects ileocecal area; may cause vasculitis, luminal thrombosis and associated severe necrotizing disease
CMV burden is low so difficult to detect these cells; stool examinations usually normal
Early and rapid colonoscopy is beneficial in transplant patients (Transplant Proc 2005;37:3059)
Frequently associated with inflammatory bowel disease, but not always pathogenic (Dig Liver Dis 2004;36:818)
Case reports: immunocompetent patient with abdominal aortic aneurysm and CMV colitis (J Clin Pathol 1998;51:475), immunocompetent elderly patient with severe proctitis (Gastroenterol Clin Biol 2004;28:73), young woman with ulcerative colitis (Scand J Gastroenterol 2003;38:119), clinical colon cancer
Gross: ulceration, discrete mass
Gross images: ulceration and erythema #1; #2; #3
Micro: smudgy intranuclear and cytoplasmic inclusions in endothelial cells, fibroblasts and smooth muscle cells; rarely in epithelial cells
Micro images: CMV inclusions #1; #2; #3; #4; #5 (immunocompetent patient); superficial ulceration; cells with enlarged nuclei containing basophilic inclusions #1; #2; figures A, B
Positive stains: CMV immunostain
DD: graft versus host disease (no viral inclusions)
References: Mod Path 1998;11:29, eMedicine
Cryptosporidium parvum colitis
Self limited disease in immunocompetent, severe explosive watery diarrhea in AIDS/immunocompromised patients
Colonic involvement less frequent than small bowel
Often overlooked in AIDS patients (Archives 2001;125:1042)
Treatment: no reliable antibiotics in immunosuppressed; in transplant patients, use antibiotics and reduction in immunosuppression (Clin Nephrol 2005;63:305)
Diagnosis: acid-fast oocyst in stool specimens
Micro: intracellular but extracytoplasmic basophilic dots three microns in diameter on luminal border of epithelial cells; also cryptitis and epithelial apoptosis (AIDS 1998;12:2459)
Micro images: various images #1; #2; small blue organisms at luminal border #1; #2; #3; oocyst in fecal smear
Positive stains: Giemsa for biopsies, acid-fast oocyst in stool
EM images: located just below plasma membrane of host
References: US Food and Drug Administration, Centers for Disease Control, eMedicine
Escherichia coli of colon
Causes various forms of colitis
Enteroaggregative E. coli
Pattern of adherence is characterized by self-agglutination, which is called aggregative adherence
Common cause of diarrhea (Clin Infect Dis 2006;43:402)
Affects infants and adults, those in developing countries, HIV+ patients, but also those without foreign travel or immunodeficiency
Fever, abdominal pain and diarrhea >14 days
EM images: various images
References: Centers for Disease Control
Enterohemorrhagic E. coli
Major foodborne pathogen (ground beef and salami, unpasteurized milk and juice, sprouts, lettuce), contact with cattle, swimming in contaminated waters
Diarrhea and vomiting; also hemorrhagic colitis (abdominal cramping, bloody diarrhea, no/low grade fever) and hemolytic uremic syndrome
Due to Shiga-like toxin in O157:H7 strains
Reportable to state health departments in US
Outbreaks: unpasteurized gouda cheese in Alberta, Canada in 2002 (Can J Public Health 2005;96:182), uncooked hamburger meat in Washington State in 1992-3 (JAMA 1994;272:1349, West J Med 1996;165:15), swallowing contaminated lake water in Oregon in 1991 (N Engl J Med 1994;331:579)
Diagnosis: PCR (Mol Cell Probes 2006;20:31), enzyme immunoassay (J Clin Microbiol 2004;42:1652)
Micro: hemorrhage and edema in lamina propria; focal necrosis of superficial epithelium, acute inflammation; may have inflammatory pseudomembranes
Micro images: various images
DD: ischemic colitis
References: US Food and Drug Administration, Wikipedia
Enteroinvasive E. coli
Causes dysentery
Similar molecular features as Shigella (Infect Immun 2004;72:5080), due to virulence plasmid that encodes determinants for entry into epithelial cells and dissemination from cell to cell
Due to contaminated cheese, water or person to person spread
Micro: bacterial invasion and destruction of colonic mucosa
References: US Food and Drug Administration
Enteropathogenic E. coli
Major cause of infant diarrhea in developing countries
Due to contaminated water or feed
Has pathogenicity island that encodes proteins which modulate the actin microtubule and intermediate filament networks to allow intimate attachment of bacteria to plasma membrane of infected enterocytes, forming attachment and effacing lesions (J Bacteriol 2006;188:3110); also have large plasmid containing cluster of genes encoding bundle-forming pili
“Atypical” cases: lack bundle-forming pili, associated with prolonged diarrhea (Emerg Infect Dis 2006;12:597)
Micro: effacement of brush border microvilli of enterocytes, no bacterial invasion, but surface adherent organisms may be identifiable
EM images: various images; E. coli pili
References: US Food and Drug Administration
Enterotoxigenic E. coli
Causes traveler’s diarrhea in 20-50% who travel from industrialized world to developing countries, and infant diarrhea in less developed countries
Due to contaminated food and water
Also an emerging causing of diarrhea in US
Due to enterotoxin (heat-labile or heat-stable) produced by non-invasive bacteria that adhere to small intestine and produce cholera-like watery diarrhea
Prevention: chemoprophylaxis with rifaximin, careful food/beverage selection (Drugs 2006;66:303)
Micro: usually no histologic changes
References: Clin Microbiol Rev 2006;19:583, Clin Microbiol Rev 2005;18:465, Centers for Disease Control, US Food and Drug Administration, World Health Organization
Case reports: Korean woman with migrating fluke into cecum and associated inflammatory reaction (AJSP 1984;8:73)
Micro images: egg in fecal smear; various images; whole mount
Case reports: 44 year old African American woman with history of AIDS and Hepatitis C and a colonic mass (Archives 2005;129:259), nonimmunocompromised patient with colonic mass (Am Surg 2004;70:959), malignant appearing colonic ulcers, cecal perforation (J Clin Pathol 1988;41:992)
Gross images: polypoid lesion of cecum
Micro: yeast within macrophages
Micro images: submucosal macrophages filled with yeast forms; figure 1-colonoscopy, 2/3-H&E, 4-GMS; liver
Positive stains: GMS
HIV/AIDS associated colitis
Associated with adenovirus, CMV, Cryptosporidium, Giardia, Histoplasma, Mycobacterium avium intracellulare, Pneumocystis, spirochetosis, Kaposi’s sarcoma
Some cases have no diagnosis even after expert review and may be due to HIV virus itself
Adenovirus and infectious causes are often overlooked on biopsies of patients with negative stool studies or no response to therapy (Archives 2001;125:1042)
Bacterial infections are best identified by stool culture
Primary AIDS related enterocolitis - causes severe diarrhea with no identifiable cause; apoptosis deep in colonic crypts resembling grade 1 graft vs. host disease
Micro: diffuse and nodular lymphoid hyperplasia with germinal centers; multinucleated giant cells and mononuclear cells within lamina propria (Mod Path 1999;12:75)
HSV (herpes simplex virus) colitis
Painful discrete ulcers, vesicles or pustular lesions in distal rectum or perianal skin
Diagnose with viral culture
Case reports: patient with common variable immunodeficiency syndrome (Eur J Gastroenterol Hepatol 2006;18:541), neonate (Pediatr Infect Dis J 2002;21:887), post-transplant (Pediatr Transplant 2001;5:374)
Micro: ulceration with neutrophils in lamina propria, cryptitis, crypt abscess, multinucleated giant cells, inclusions in anal transition zone epithelium and perianal skin
Micro images: esophagus
Infectious (acute self limited) colitis
Acute self-limited colitis may be due to infections, drugs or gluteraldehyde disinfection of endoscope (Endoscopy 1998;30:428)
May not always be self-limited
Due to (a) ingestion of pre-formed toxins (Staphylococcus aureus, Vibrio cholera, Clostridium perfringens, causes symptoms within hours including explosive diarrhea), (b) infection by toxigenic organisms (incubation of hours or days) or (c) infection by enteroinvasive organisms which invade and destroy mucosal epithelium cells
Bacterial virulence factors include (a) adherence to epithelial cells, (b) enterotoxins, (c) invasion factors, (d) cytotoxicity
(a) Adherence: via fimbriae or pili; the process of adherence destroys the microvilli brush border
(b) Enterotoxins: toxin binds to cell membrane, enters cell, activates massive electrolyte secretion (cholera toxin, E. coli heat-labile and heat-stable toxins produce travelers diarrhea); no white blood cells in stool
(c) Invasion factors: enteroinvasive E. coli and Shigella invade via microbe-simulated endocytosis; then intracellular proliferation, cell lysis, cell to cell spread
(d) Cytotoxicity: Shiga toxin, enterohemorrhagic E. coli
Complications: due to massive fluid loss and loss of mucosal barrier; include dehydration, sepsis, perforation
Micro: inflammation of lamina propria (active much greater than chronic), edema, hemorrhage; severe cases have crypt abscesses, extensive necrosis, hemorrhage and thrombi
Micro images: infectious colitis #1; #2; #3; #4; #5; #6; #7; #8; #9; mild superficial increase in chronic inflammation;
DD: ulcerative colitis (crypt distortion, plasma cells at base of crypts, AJSP 1982;6:523)
Mycobacteria infections of colon other than tuberculosis
Associated with HIV infection; recommended to perform acid-fast stain on all mucosal biopsies in HIV+ patients
If present in gut, is usually disseminated, with positive stool and blood cultures
May be due to contaminated endoscope (Kekkaku 1995;70:629)
Case reports: causing severe GI bleeding in immunosuppressed patient (Am J Gastroenterol 1999;94:232), M. xenopi causing colonic stricture (Postgrad Med J 2003;79:705)
Micro: macrophages with cytoplasmic rods filling lamina propria; resembles Whipple’s disease but without fat vacuoles
Micro images: histiocytes with finely granular cytoplasm #1; #2; #3; #4; PAS; Ziehl-Neelsen acid-fast stain; acid-fast stain #1; #2; #3; #4; figure F
Positive stains: acid-fast, PAS (faintly positive bacillary forms)
Rotavirus of colon
Most common cause of gastroenteritis in infants and young children worldwide
Usually self-limited disease in US, although major cause of childhood death (up to 500K annual deaths) in developing countries
Varies from mild watery diarrhea to severe diarrhea leading to dehydration and shock
Vaccine licensed for US infants in 2006 (MMWR Recomm Rep 2006;55:1)
Case reports: fatal cases in young children due to diffuse endotheliatis and associated tissue damage (Hum Path 2001;32:216), outbreak in a transplant unit (Transpl Int 2005;18:470)
Diagnosis: enzyme immunoassay
Micro images: B cells in lamina propria
Salmonella of colon
Usually affects terminal ileum, occasionally colon
Invades via transcytosis with minimal epithelial damage
Due to contaminated milk, eggs, beef, poultry
Causes dysentery, bacteremia (see typhoid fever)
Case reports: causing toxic megacolon (Int J Colorectal Dis 2002;17:275, Acta Paediatr Taiwan 2000;41:43), causing obstruction (Pediatr Surg Int 2000;16:525), Salmonella dublin causing spontaneous bacterial peritonitis in cirrhosis patient (Eur J Gastroenterol Hepatol 2001;13:587)
Micro: mild cases show colonic mucosal edema with acute inflammation but preservation of crypt architecture; occasional crypt abscesses; severe cases show neutrophils invading degenerating crypts with possible microthrombi and mucus depletion
DD: ulcerative colitis (Histopathology 1978;2:117)
References: AJSP 1979;3:483, eMedicine #1, #2, Centers for Disease Control
Schistosomiasis of colon
Fluke that causes colitis or bowel obstruction
Associated with underdeveloped countries, and living near dam reservoirs (Lancet Infect Dis 2006;6:411)
S. haematobium: Africa and Middle East; usually affects bladder; diagnosed with urine examination
S. intercalatum: central West Africa; uncommon
S.
japonicum: Southeast Asia and western Pacific countries;
diagnose with stool examination
S. mansoni: South America, Caribbean, Africa and Middle East; diagnose
with stool examination
S. mekongi: Southeast Asia; uncommon
Case reports: 78 year old man with rectal adenocarcinoma, with endometriosis (Fertil Steril 2006;85:1060.e1)
Gross images: Schistosoma granulomas
Micro: focal ulcers, eggs may be calcified, surrounded by fibrosis or surrounded by granuloma
Micro:
S. haematobium - eggs are 110-170 x 40-70 microns, oval with terminal spine
S. japonicum
- eggs are 70-100 x 55-65 microns,
oval/round (more rounded than other types), minute subterminal or no spine
S. mansoni - eggs are 110-175 by 45-70 microns with thin transparent shell and definite lateral spine
Micro images: S. mansoni and S. japonicum
S. haematobium - fluke; eggs #1; #2; #3; #4
S. japonicum - fluke; eggs #1; #2; #3
S. mansoni - fluke #1; #2; eggs #1; #2; #3
within tissue, type not identifiable - #1; #2; #3; granuloma surrounding egg
Micro images contributed by Dr. Lisa Cerilli: within colonic mucosa #1; #2; #3; #4; #5; #6
Virtual slides: schistosomiasis
References: eMedicine #1, #2, Centers for Disease Control, Wikipedia, World Health Organization, Archives 2005;129:544 (S. mansoni)
Shigella of colon
Invades distal colon
Low inoculum needed to cause disease
Person to person spread; can occur in epidemics
Produces purulent exudates, dysentery
Gross: colonic mucosal damage and ulceration
Gross images: Shigella colitis
Micro: marked acute and chronic inflammatory mucosal infiltrate, with ulceration, epithelial cell necrosis, mucus depletion and hemorrhage; occasional crypt abscesses
Virtual slides: dysentery (organism not identified)
References: Centers for Disease Control, University of Texas Medical Branch, eMedicine #1, #2
Spirochetosis of colon
Colonization of colon by relatively non-pathogenic spirochetes
Seen in 3-10% of normal patients; associated with anal intercourse (present in 30% of male homosexuals), HIV, lower socioeconomic conditions
May cause persistent diarrhea, possibly due to blunting and destruction of microvilli (AJCP 1986;86:679)
Best characterized species are Brachyspira aalborgi and Serpulina pilosicoli
Case reports: 2 year old with failure to thrive, HIV patient with CMV colitis
Treatment: metronidazole if symptomatic
Micro: spirochetes accentuate luminal border (by embedding into enterocytes in parallel alignment), produces blue haematoxyphilic line between the microvilli of the covering epithelium (Pathologe 2003;24:192); minimal inflammation
Micro images: accentuation of luminal border #1; #2; #3; #4; various images #1; #2; Warthin-Starry #1; #2; #3
Positive stains: silver stains (Warthin-Starry, Dieterle, Churukian-Schenk), PAS, Giemsa, Alcian-blue (pH 2.5)
EM images: long coiled bacteria are adherent to microvilli
References: Archives 2001;125:699, AJCP 2003;120:828
Typically associated with immunodeficiency and small intestinal or pulmonary manifestations
Few larvae present in colon, may delay diagnosis due to difficulty in identification (Ann Diagn Pathol 2003;7:87)
Case reports: nonimmunocompromised man with diarrhea, weight loss and microcytic anemia (J Clin Gastroenterol 1999;28:77), mimicking ulcerative colitis (J R Coll Surg Edinb 1997;42:202), causing chronic colitis (Am J Trop Med Hyg 1983;32:1289), pseudopolyposis (Surg Endosc 1987;1:175), presenting with massive bleeding (Arch Intern Med 1980;140:1061), bowel infarction (Trans R Soc Trop Med Hyg 1975;69:473)
Gross images: adult female worm
Micro: rarely see eosinophilic granulomatous inflammation of colon wall clinically resembling inflammatory bowel disease (AJSP 1996;20:693)
Micro images: larvae in stool
Syphilis of colon
Case report: primary syphilis in rectum (J Korean Med Sci 2005;20:886)
Micro: obliterative endarteritis with plasma cells; variable granulomas
Micro images: obliterative endarteritis with plasma cells (figure 1)
Trichuriasis of colon
Due to Trichuris trichiura (whipworm)
Symptoms vary from none to bloody diarrhea
May cause rectal prolapse in children
May mimic acute appendicitis
Case reports: bloody diarrhea due to massive infestation (J Trop Pediatr 2006;52:66), resembling a sessile polyp (Ital J Gastroenterol Hepatol 1997;29:365)
Gross images: infestation with mucosal hemorrhage
Micro: focal ulcers; adult worms present
Micro images: worm #1; #2 (figure 2)
EM images: worm
References: eMedicine, Centers for Disease Control
Tuberculosis of colon
May involve GI tract even with minimal or inactive pulmonary disease (Hong Kong Med J 2006;12:264), usually small intestine and ileocecal area (Gastroenterol Clin Biol 2005;29:419)
Diagnosis may be difficult and require exploratory laparoscopy (Scand J Gastroenterol 2005;40:240)
Pain, diarrhea, weight loss, fever
50% have palpable mass; may cause obstruction and stricture (Endoscopy 2004;36:1099); peritonitis rare
Case reports: colonic perforation (Dis Colon Rectum 2004;47:2211), massive melena (Int J Clin Pract 2004;58:1162), high adenosine deaminase in ascites fluid (Kansenshogaku Zasshi 2004;78:916), coexisting carcinoma (Trop Gastroenterol 2003;24:137), treated initially as Crohn’s disease (World J Gastroenterol 2003;9:2382)
Treatment: surgery for cecal masses or perforation, antibiotics
Gross: ulceration, diffuse fibrosis through colonic wall
Gross images: tuberculosis #1; #2
Micro: caseating or noncaseating granulomas, ulceration and desmoplasia; variable vasculitis, mural fibrosis, granulomas in mesenteric lymph nodes
Micro images: various images; mucosal granulomas #1; #2 (figure 1)
Positive stains: acid fast bacilli
DD: Crohn’s disease (much more common in US and western Europe, no acid fast bacilli, no caseation, no coalescing granulomas)
References: eMedicine
Typhoid fever of colon
Due to Salmonella typhi, which enters epithelial cells via cystic fibrosis transmembrane conductance regulator (CFTR mutations cause cystic fibrosis, Nature 1998;393:79)
Causes bacteremia, fever, chronic infection of joints, biliary tree, bones and meninges
Causes intestinal bleeding due to ulcers in distal ileum or proximal colon (Dig Liver Dis 2004;36:141); bleeding may be massive (Dis Colon Rectum 1986;29:511)
Case reports: colonic perforation (J Coll Physicians Surg Pak 2004;14:634), toxic megacolon (Acta Paediatr Taiwan 2000;41:43), skip ulcers (J Gastroenterol 1999;34:700), splenic abscess and colonic fistula (Gastroenterol Clin Biol 1998;22:1102)
Gross images: perforation at site of Peyer’s patches
Micro: hyperplasia, mucosal necrosis and sloughing, ulceration; macrophages contain bacteria, red blood cells and lymphocytes; macrophage aggregates are called typhoid nodules, present in intestine and nodes (also other sites);
Micro images: typhoid nodules (microgranulomas) in ileal wall
References: eMedicine #1, #2
Vibrio cholera of colon
Produces enterotoxin that causes profuse watery diarrhea; bacteria is not invasive
From contaminated water or shellfish, causes pandemics by person-to-person contact
Treatment: oral rehydration and adequate sanitation; antibiotics or vaccines do not have a major role
References: Centers for Disease Control, Wikipedia, World Health Organization, University of Wisconsin, eMedicine
Yersinia infections of colon
Yersinia enterocolitica
Causes diarrhea (mild self limited to typhoid fever-like disease), may cause peritonitis, pharyngitis, pericarditis
From contaminated milk or pork
Invades ileal mucosa, multiplies in Peyer’s patches and regional lymph nodes; also affects right colon and appendix
May cause arthritis (Clin Infect Dis 1997;25:831); may trigger collagenous colitis in some cases (Dig Dis Sci 1998;43:1341, Scand J Gastroenterol 2002;37:711)
Case reports: infection in patient with hemachromatosis simulating colon cancer with liver metastases (Dis Colon Rectum 2005;48:390), simulating Crohn’s disease (Pediatrics 1999;104:e36), causing colonic abscess (Dis Colon Rectum 1990;33:985)
Micro: ulcers overlying lymphoid nodules, necrotizing microgranulomas
Micro images: various images
Gram stain: gram negative rods; aerobic and motile
References: eMedicine #1, #2, infections in Norway, US Food and Drug Administration
Yersinia pseudotuberculosis
Micro: similar to Y. enterocolitis plus true granulomas with neutrophilic core
References: eMedicine, outbreak in British Columbia, Canada
Non-neoplastic, non-congenital lesions
Adhesions of colon
Cause hospital admissions in up to 1/3 within 10 years of colorectal surgery (Dis Colon Rectum 2001;44:822)
Also due to infections and endometriosis
Commonly occur between bowel segments or abdominal wall and operative site
May create internal herniations (closed loops through which viscera slide)
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