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Gross, EM and immunohistochemistry images are needed for most disorders

Micro images are particularly needed for these lesions:

Congenital - intestinal neuronal dysplasia

Colitis (non-infectious) - allergic colitis, Brainerd diarrhea, diversion colitis, hemorrhagic colitis, pouchitis, radiation enterocolitis, typhlitis

Colitis (infectious) - Candida, Chagas disease, Clostridium botulinum, HIV/AIDS, HSV, Shigella, typhoid fever, Vibrio cholera, Yersinia

Non-neoplastic, non-congenital - adhesions, brown bowel, colchicine toxicity, colitis cystica profunda, gout, hyperplastic Pacinian corpuscle, idiopathic constipation, infracted epiploic appendages, reactive angioendotheliomatosis, xanthelasma

Embryology of colon

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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

References: more information, Early Hum Dev 2004;78:1

Normal anatomy of colon

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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

Cecum: in peritoneum, 6 x 9 cm; large blind pouch arising from proximal right colon; blind end directed downward, open end directed upward

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

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

Pouch of Douglas: cul-de-sac in women made up of reflection of peritoneum from the rectum over the pelvic wall

Taenia coli: discontinuous muscular fibers

Epiploic appendages: pedunculated fat on lateral colon; lined by mesothelium

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

Normal histology of colon

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Composed of mucosa, submucosa, muscularis propria (externa) and serosa (perimuscular tissue in rectum)

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

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

Submucosa: loose connective tissue with submucosal plexus of Meissner; minimal inflammatory infiltrate; younger patients may have intramucosal lymphoid aggregates that disrupt muscularis mucosa

Muscularis propria: inner circular layer, myenteric plexus of Auerbach, outer longitudinal layer

Serosa: single layer of flat to low cuboidal mesothelial cells and adjacent fibroelastic tissue

Types of cells

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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)

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

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

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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

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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

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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; #2

Treatment: segmental resection and anastomosis; good prognosis with prompt treatment (J Pediatr Surg 2005;40:1258)

References: eMedicine

Chronic intestinal pseudo-obstruction

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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)

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

Cyst of retrorectal space

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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

References: Radiographics 2001;21:575-adults, Archives 2000;124:725-cystic hamartoma, retrorectal tumors

Duplication of colon

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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)

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

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Commonly causes constipation

Case reports: fecal impaction causing toxic megacolon and death from perforation (BMC Dermatol 2006;6:2)

Gastroschisis

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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

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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)

Hirschsprung’s disease of colon

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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

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)

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

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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)

Malrotation of colon

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From improper embryologic rotation of gut

Symptoms may first occur in women during pregnancy (Obstet Gynecol 1993;81:817)

References: eMedicine

Omphalocele

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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)

DD: gastroschisis (not through umbilical cord, no membranous sac covering intestines)

References: eMedicine #1; #2

Diverticular disease of colon

Diverticulosis

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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

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

DD: Crohn’s disease if fistulas present (has mucosal ulceration, lymphoid aggregates distant from inflamed diverticula)

References: AJCP 1997;107:438

Diverticulitis

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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)

Micro: acute or chronic inflammatory infiltrate near base of diverticula; occasionally granulomatous inflammation

DD: Crohn’s disease (although both may coexist)

References: eMedicine #1; #2

Inflammatory bowel disease (IBD)

Inflammatory bowel disease-general

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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

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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)

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

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

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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

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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 featuresof ulcerative colitis or Crohn’s disease were obscuredby 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

References: J Clin Pathol 2004;57:1233

Dysplasia in inflammatory bowel disease

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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

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

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

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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 presentationin 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

Ulcerative colitis of colon - continued

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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

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

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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

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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

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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

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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

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

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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

DD: polypoid colonic carcinoma

Colitis (non-infectious)

General

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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

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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

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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

Allergic colitis

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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

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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

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

References: Clin Microbiol Rev 2005;18:247 (mechanism of action of toxins), Merck manual, eMedicine #1, #2

Behcet’s syndrome of colon

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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

DD: Crohn’s colitis

References: eMedicine #1, #2

Brainerd diarrhea

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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

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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);

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

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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

DD: Clostridium difficile infection (Dis Colon Rectum 2006;49:1074)

References: AJSP 1990;14:548, Hum Pathol 1990;21:429

Diverticular colitis

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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

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

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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

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)

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)

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

Granulomatous colitis

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Causes: Crohn’s disease, tuberculosis, Yersinia

Case reports: due to Propionibacterium acnes, a low virulence skin bacteria (Archives 2001;125:1491)

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)

Hemorrhagic colitis

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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

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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

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

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 associated colitis

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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

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

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“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)

DD: bowel preparation changes, drug reaction, Hashimoto’s thyroiditis, Brainerd diarrhea, inflammatory bowel disease

References: eMedicine

Paucicellular variant

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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

Lymphoid follicular proctitis

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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

References: Dig Dis Sci 1988;33:314

Malakoplakia of colon

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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

Mastocytic enterocolitis

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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

Positive stains: tryptase

DD: ulcerative colitis with mast cells

Necrotizing enterocolitis

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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

Micro: early - mucosal edema, hemorrhage, necrosis, pneumatosis cystoides intestinalis; late - hemorrhagic and gangrenous bowel wall with strictures if patient survives

References: J Clin Pathol 1979;32:1090, Northwestern University (Illinois, USA), eMedicine #1, #2

NSAID associated colitis

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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

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

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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

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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)

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

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

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Acute or chronic

May be side effect of radiation therapy for cervical, prostate or rectal carcinoma

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)

Micro: atrophic mucosa, ectatic vessels in lamina propria, vascular injury (intimal fibroplasia, foamy macrophages and hyaline within vessel walls), ischemic fibrosis, stricture

Talc in colon

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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

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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

Micro: adherent fibrinopurulent exudate over necrotic and edematous mucosa

References: eMedicine

Infectious colitis (specific microorganisms)

Actinomycosis of colon

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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)

References: eMedicine #1; #2

Adenovirus colitis

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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

Positive stains: adenovirus immunostain

Amebic colitis

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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)

Gross: discrete areas of ulceration covered by exudate with normal intervening mucosa

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

Positive stains: PAS

References: Clin Microbiol Rev 2000;13:318 (pathogenesis), eMedicine #1, #2

Balantidiasis of colon

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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)

Micro: flask shaped ulcers containing green-yellow trophozoites (60 x 35 microns)

EM: flattened oval organism covered with cilia with gullet at anterior end

References: eMedicine

Basidiobolomycosis

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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)

References: University of Adelaide

Campylobacter jejuni of colon

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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

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

Candida

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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)

Chagas disease (trypanosomiasis) of colon

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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)

Micro: mast cells and fibrosis (Rev Soc Bras Med Trop 2003;36:461)

References: Mem Inst Oswaldo Cruz 2003;98:577, Emedicine #1, #2, World Health Organization, University of South Carolina

Clostridium botulinum of colon

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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

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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 #1, #2 in AIDS patient

Gross: ulceration, discrete mass

Micro: smudgy intranuclear and cytoplasmic inclusions in endothelial cells, fibroblasts and smooth muscle cells; rarely in epithelial cells

Positive stains: CMV immunostain

DD: graft versus host disease (no viral inclusions)

References: Mod Path 1998;11:29, eMedicine

Cryptosporidium parvum colitis

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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)

Positive stains: Giemsa for biopsies, acid-fast oocyst in stool

References: US Food and Drug Administration, Centers for Disease Control, eMedicine

Escherichia coli of colon

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Causes various forms of colitis

Enteroaggregative E. coli

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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

References: Centers for Disease Control

Enterohemorrhagic E. coli

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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

DD: ischemic colitis

References: US Food and Drug Administration, Wikipedia

Enteroinvasive E. coli

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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

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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

References: US Food and Drug Administration

Enterotoxigenic E. coli

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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

Fasciola associated colitis

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Case reports: Korean woman with migrating fluke into cecum and associated inflammatory reaction (AJSP 1984;8:73)

Histoplasmosis of colon

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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)

Micro: yeast within macrophages

Positive stains: GMS

HIV/AIDS associated colitis

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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

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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

Infectious (acute self limited) colitis

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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

DD: ulcerative colitis (crypt distortion, plasma cells at base of crypts, AJSP 1982;6:523)

Mycobacteria infections of colon other than tuberculosis

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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

Positive stains: acid-fast, PAS (faintly positive bacillary forms)

Rotavirus of colon

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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

Salmonella of colon

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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

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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)

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

References: eMedicine #1, #2, Centers for Disease Control, Wikipedia, World Health Organization, Archives 2005;129:544 (S. mansoni)

Shigella of colon

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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

Micro: marked acute and chronic inflammatory mucosal infiltrate, with ulceration, epithelial cell necrosis, mucus depletion and hemorrhage; occasional crypt abscesses

References: Centers for Disease Control, University of Texas Medical Branch, eMedicine #1, #2

Spirochetosis of colon

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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

Positive stains: silver stains (Warthin-Starry, Dieterle, Churukian-Schenk), PAS, Giemsa, Alcian-blue (pH 2.5)

References: Archives 2001;125:699, AJCP 2003;120:828

Strongyloides stercoralis

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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)

Micro: rarely see eosinophilic granulomatous inflammation of colon wall clinically resembling inflammatory bowel disease (AJSP 1996;20:693)

Syphilis of colon

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Case report: primary syphilis in rectum (J Korean Med Sci 2005;20:886)

Micro: obliterative endarteritis with plasma cells; variable granulomas

Trichuriasis of colon

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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)

Micro: focal ulcers; adult worms present

References: eMedicine, Centers for Disease Control

Tuberculosis of colon

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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

Micro: caseating or noncaseating granulomas, ulceration and desmoplasia; variable vasculitis, mural fibrosis, granulomas in mesenteric lymph nodes

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

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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)

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);

References: eMedicine #1, #2

Vibrio cholera of colon

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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

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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

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

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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)

Rarely are congenital

Rarely cause colonic obstruction (Am Surg 1984;50:479)

Amyloidosis of colon

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Diagnose with rectal biopsy that includes submucosa

Amyloid tumor may clinically resemble carcinoma (AJR Am J Roentgenol 2002;179:536)

Associated with hemodialysis (Gastroenterology 1989;96:230, Clin Nephrol 2000;53:394, Mod Pathol 1995;8:577)

Rarely AL amyloid is localized to colon, and does not require systemic treatment (Amyloid 2003;10:36)

Case reports: amyloid tumor with synchronous adenocarcinoma (J Clin Pathol 1995;48:592)

Micro: amyloid present in blood vessel walls and muscularis propria; may be subepithelial; may cause ischemic changes in colon

DD: collagenous colitis (surface epithelial damage, epithelial lymphocytes)

Angiolymphoid hyperplasia with eosinophilia in colon

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Also called epithelioid hemangioma

Usually skin; rare in colon with only one case report

Case reports: 63 year old man with severe GI hemorrhage requiring hemicolectomy (J Clin Pathol 1997;50:611)

Micro: sheet of lymphocytes and eosinophils associated with vessels containing plump and pleomorphic endothelial cells

Barium granuloma of colon

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Rare; may occur after barium enema if barium penetrates mucosal tear and stimulates a granulomatous reaction

Crystals are visible under polarized light

Usually an incidental finding; rarely produces polypoid or ulcerated lesion resembling a neoplasm

Case reports: rectum (Ann Surg 1975;181:418), rectum (reprint of 1954 article)

Micro: barium is green, crystalline and refractile; crystals occur in clusters in macrophages or connective tissue

References: Histol Histopathol 1992;7:625

Blue/green colon

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Autopsy finding associated with enteral feeding containing food coloring (Archives 2000;124:1397, Archives 2001;125:599)

Food coloring is used to identify either aspirated gastric contents in suctioned airway fluids or the source of fistulous drainage

Brown bowel

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Also called ceroidosis

Rare; affects small or large intestine with lipofuscin deposits in smooth muscle cells of muscularis propria, occasionally muscularis mucosa and vessel walls (Cesk Patol 1994;30:23)

Vitamin E deficiency, secondary to malnutrition (Am J Gastroenterol 1996;91:1450, J Formos Med Assoc 1993;92:1090), or celiac sprue (Rev Esp Enferm Dig 1993;83:281, Med Wieku Rozwoj 2003;7:593) causes mitochondrial myopathy affecting smooth muscle of GI tract, leading to atonic and dilated bowel and pseudoobstruction (Archives 1990;114:76); lipofuscin deposits reflect mitochondrial injury

Case reports: anorectal functional deficit (Ir J Med Sci 1994;163:404), associated with GI adenocarcinoma (J Clin Gastroenterol 1993;16:48)

Treatment: vitamin E, resection of affected bowel

Gross: dark brown or orange-brown discoloration of bowel wall, which is often dilated

Micro: lipofuscin deposits in muscularis propria and muscularis mucosa

Positive stains: PAS, golden-yellow autofluorescence under ultraviolet light

EM: degradation of smooth muscle mitochondria (Scand J Gastroenterol 1990;25:66)

DD: melanosis coli, blue/green colon

References: Am Surg 1989;55:566, J Clin Pathol 1987;40:798

Colchicine toxicity of colon

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Colchicine is used to treat gout, constipation (Am J Gastroenterol 2003;98:1112) and other disorders

Case reports: accidental ingestion of meadow saffron / autumn crocus / naked lady, which contains colchicine (J Forensic Sci 2002;47:1391), colchicine effect in hyperplastic polyp (Archives 2002;126:615)

Micro: abundant epithelial mitotic figures with metaphase arrest; often enlarged epithelial cells with condensed chromatin in a ring formation within center of cell; associated with epithelial loss of polarity and pseudostratification; nuclei small, hyperchromatic and compressed to periphery of cell

References: AJSP 2001;25:1067

Colitis cystica profunda

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Uncommon

Cysts containing mucus in colonic submucosa; either localized or diffuse

Similar histology to colorectal polyps in Cowden’s syndrome

Localized: called hamartomatous inverted polyp, localized 5-12 cm from anal margin, presents as nodule or plaque, associated with chronic proctitis

Diffuse: secondary to ulcerative colitis, Crohn’s disease, radiation or other inflammation / ulceration of bowel; mucus follows granulation tracts to involve large areas of bowel

Case reports: after radiation for bladder carcinoma (Archives 1995;119:1170), recurrence after 20 years (Chir Ital 2005;57:789), nodular lesion at colostomy stoma for uterine cancer

Treatment: patient education to avoid straining, high fiber diet with bulk laxatives, surgery for rectal prolapse (Current Treatment Options in Gastroenterology 2002;5:231)

DD: mucinous adenocarcinoma or colloid carcinoma (infiltrating, epithelium floats in mucin, glandular atypia, tumor desmoplasia, no hemorrhage or hemosiderin, no lamina propria), ulcerative colitis (no fibromuscular obliteration of lamina propria)

Endometriosis of colon

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Usually incidental

Commonly involves colonic wall (15% of cases), usually rectosigmoid or rectovaginal septum (Med Sci Monit 2000;6:787)

Rarely associated with neoplasms or precancerous changes (AJSP 2000;24:513)

Case reports: with schistosomiasis (Fertil Steril 2006;85:1060.e1), causing obstruction of sigmoid colon (Ugeskr Laeger 2005;167:3604), with endometrioid adenocarcinoma (Am Surg 2005;71:694), with endometrial stroma sarcoma (J Korean Med Sci 2002;17:412), with clear cell carcinoma (J Clin Pathol 2001;54:76), with mixed germ cell tumor (AJCP 1982;78:555)

Gross: serosa and subserosa nodules < 5 cm; smooth muscle hypertrophy may cause obstruction; gray cut surface with minute areas of hemorrhage

Micro: endometrial glands, stroma, hemosiderin in deeper layers; usually surrounded by smooth muscle; epithelium may have inflammation and ulcers simulating inflammatory bowel disease or solitary rectal ulcer syndrome; often infiltrates along nerves of bowel wall (Hum Reprod 2004;19:996), mucosa usually normal; bowel wall may be fibrotic

Negative stains: CEA

DD: adenocarcinoma (BMC Gastroenterol 2003;3:18)

Fibrosing colonopathy

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Fusiform strictures of colon associated with childhood cystic fibrosis

May be due to ingestion of high strength pancreatic supplements

Affects right colon or entire colon

Case reports: in adult long after discontinuance of pancreatic enzymes (South Med J 2004;97:901), in newborn with cystic fibrosis before receiving enzymes (J Pediatr Gastroenterol Nutr 2002;35:356)

Gross: cobblestone appearance

Micro: severe submucosal fibrosis with thickening of muscularis propria and chronic mucosal inflammation, including eosinophils and mast cells; variable active cryptitis

References: Hum Path 1997;28:395

Florid vascular proliferation of colon

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Associated with lipomas causing intussusception (Pathol Int 2005;55:160, J Clin Pathol 1993;46:91) or obstruction (Am Surg 2001;67:491); also HIV, arteriovenous malformation

Benign, appears reactive

Gross: colonic mass

Micro: florid lobular proliferation of small vascular channels lined by plump endothelial cells in submucosa or muscular wall; minimal/no atypia, no/rare mitotic figures present; mucosal ulceration and muscular fibroplasia in adjacent lamina propria suggest mucosal prolapse; often ischemic type changes

DD: angiosarcoma

References: Mod Path 2001;14:1114

Gastric heterotopia of colon

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Often in rectum, <50 cases reported

Associated with other heterotopia, vertebral and digital anomalies

Mean age 18 years but wide range

In rectum, usually presents with rectal bleeding and tenesmus (J Clin Gastroenterol 1994;19:41)

Case reports: rectum (Archives 1999;123:222), associated with tubulovillous adenoma (N J Med 1995;92:512)

Treatment: excision, H2 blockers

Gout in colon

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Very rare

Case report: 37 year old black woman with SLE, diabetes, hypertension and tophus in colon (Hum Path 2004;35:897)

Hemorrhoids

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See Anus and perianal area Chapter

Hyperplastic Pacinian corpuscle of colon

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Rare; intraabdominal Pacinian corpuscles may enlarge up to 1 cm

Micro: resembles cutaneous counterpart with central blood vessel and nerve ending surrounded by 14-45 tortuous, concentric lamellae

DD: nematode (has cuticle, internal structures)

Idiopathic constipation

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Severe and persistent constipation without a known cause

Cathartic colon is historic term for anatomic changes due to chronic laxative use

Usually women

Affects 5-30% in UK (Nurs Times 2005;101:59)

Treatment: may require colectomy

Gross: loss of haustral folds (J Clin Gastroenterol 1998;26:283)

Micro: melanosis coli due to laxative use; may have loss of neurons in myenteric plexus with silver stains; may have reduced CD117+ interstitial cells of Cajal

Cathartic colon: mucosa resembles snake skin, atrophic muscularis propria with decreased neurons in Auerbach plexus

References: National Institutes of Health

Infarct of colon

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Case reports: due to giant cell arteritis (Medicina (B Aires) 1999;59:86), abdominal aortic aneurysm (Minerva Chir 1996;51:597)

Infarcted epiploic appendages

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Due to twisting of normally think pedicles of fat on lateral colon

May be associated with obstruction and abscess (J Am Assoc Gynecol Laparosc 1996;3:325)

Gross: firm, gray-white nodules resembling metastatic tumor

Micro: central infarcted adipose tissue with peripheral fat necrosis and calcification, outer fibrotic and inflamed tissue

Melanosis coli

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Common endoscopic finding

Grossly visible brown-black areas of colon after ingestion of anthracene-type laxatives

Typically involves all parts of colon and rectum, but spares mucosal regions with lymphoid nodules, polyps or carcinomas; thus, should biopsy nonpigmented regions in these patients

No associated with adenomas, although small polyps are more easily identified (Z Gastroenterol 1997;35:313)

Case reports: patient with Rett syndrome (autonomic neuropathy, constipation, severe CNS disease, Archives 2001;125:1110), in pericolonic nodes of patient taking laxative (Archives 2004;128:565)

Micro: macrophages containing lipofuscin (melanin-like pigment) in lamina propria; silver stains may show abnormalities of myenteric plexus

Pneumatosis cystoides intestinalis

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Submucosal gas-filled cysts in GI tract; called mucosal pseudolipomatosis if it resembles lipomatosis (AJCP 1985;84:575)

Either benign or fulminant form

In infants, fulminant form is associated with necrotizing enterocolitis and may be fatal; also associated with cystic fibrosis or congenital heart defects

In adults, either idiopathic or associated with obstruction, chronic lung disease, scleroderma (Am J Med Sci 2006;332:100), chemotherapy, drugs, ischemic colitis

Often indolent clinical course, although radiographically resembles carcinoma

Considered a finding, not a diagnosis

Treatment: surgery if bowel necrosis, perforation or peritonitis

Gross: polypoid grapelike masses protrude through mucosa

Micro: submucosal cysts lined by multinucleated giant cells; mucosa contains cryptitis, crypt abscesses, granulomas; may also resemble lipomatosis

DD: Crohn’s disease

References: Archives 1999;123:354, eMedicine

Reactive angioendotheliomatosis of colon

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Case report: 19 year old Japanese male with Crohn’s disease and no cutaneous intravascular proliferations (AJSP 2004;28:257)

Micro: intravascular proliferation of endothelial cells resembling glomeruloid hemangioma

Solitary rectal ulcer syndrome

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Also called mucosal prolapse syndrome (may be a better term since not necessarily solitary, ulcerated or rectal)

Rare; incidence of 1 per 100K per year

Similar to inflammatory cloacogenic polyp (lower rectum and anal transition zone)

Solitary or multiple ulcerated or polypoid lesions 4-18 cm from anal margin; may occur in anal canal or sigmoid

Usually age 20’s to 30’s, rarely in children (Pediatrics 2002;110:e79)

Often abnormal function of anal and pelvic floor musculature during defecation, causing rectal mucosal prolapse or intussusception

Associated with histologic changes of sessile serrated polyps (38%), which often have focal loss of hMLH1 gene expression (Archives 2005;129:1037)

Symptoms: constipation, blood and mucus from rectum, change in bowel habits, pain

Case reports: 41 year old man with rectal nodule

Treatment: reassurance, high fiber diet, laxatives, topic steroids

Gross: well demarcated irregular ulcer(s) on rectal wall; also polypoid, rough, erythematous lesions; mucosal thickening

Micro: superficial mucosal ulceration and villiform change, crypt hyperplasia and elongation with focal dilation (some diamond shaped), proliferation of fibroblasts and smooth muscle cells in edematous lamina propria, thickened muscularis mucosa with splayed fibers, ectatic capillaries, minimal inflammation; may have inflammatory pseudomembranes; late changes resemble colitis cystica profunda

DD: ulcers due to ergotamine suppositories, rectal endometriosis (Mod Path 1995;8:599), Cowden’s disease (same histology, different clinical features), mucinous adenocarcinoma (irregular mucin pools, epithelium floating in mucin, complex glandular proliferation, variable atypia, desmoplasia, usually no hemorrhage), ulcerative proctitis, Crohn’s disease

Vascular ectasia of colon

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Also called angiodysplasia, arteriovenous malformation

Prevalence < 1%, but accounts for 20% of patients with lower GI bleeding

Often in elderly

Usually right colon, usually acquired

May be associated with aortic stenosis or von Willebrand disease

Bleeding is due to minimal number of cells between lumen and vessels

Case reports: associated with myelofibrosis (J Clin Pathol 2004;57:999), 22 year old woman (Indian J Pathol Microbiol 2006;49:34)

Treatment: electrocoagulation (Gastrointest Endosc 2006;64:424) or surgery

Gross: tortuous dilation of submucosal and mucosal blood vessels containing small amounts of smooth muscle; small, multiple, easier to identify by arteriography than in surgical specimen unless inject with silicone rubber and clear with methyl salicylate

Micro: dilated and thin walled vessels, often with cholesterol emboli, particularly in submucosa

DD: colonic varices due to portal hypertension

References: J Clin Pathol 1982;35:824, eMedicine

Vasculitis of colon

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Common causes are polyarteritis, phlebitis, Churg-Strauss syndrome (Hepatogastroenterology 1997;44:1090), small vessel vasculitis (AJSP 1995;19:338), leukocytoclastic vasculitis (Wien Klin Wochenschr 2005;117:565, Dis Colon Rectum 2005;48:167)

Intramural phlebitis (enterocolic lymphocytic phlebitis)

May cause ischemic intestinal necrosis and resection (AJSP 1989;13:303)

Some cases associated with use of hydroxyethyl rutozide; others of unknown origin

No association with systemic vasculitis

Case reports: associated with flutamide (AJSP 2004;28:542), isolated mesocolic vasculitis (AJSP 2001;25:827), thickened serosal presenting as abdominal mass (J Clin Gastroenterol 2002;34:252)

Diagnostic criteria: predominantly lymphocytic infiltration of intramural tributaries of mesenteric veins

Micro: phlebitis affecting all layers of bowel wall, numerous associated thrombi; may have myointimal hyperplasia of affected mesenteric veins (AJSP 1994;18:779); arterioles and arteries not affected

References: AJSP 2000;24:824, Mod Path 2000;13:897, USCAP Short Course

Volvulus of colon

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Complete twisting of loop of bowel around its mesenteric base of attachment, causing obstruction and infarction

Usually involves cecum or sigmoid (Can J Surg 2006;49:203)

Gangrene may extend beyond constriction (Int J Colorectal Dis 2004;19:134)

Treatment: surgical exploration to untwist and resect gangrenous bowel

References: eMedicine, American Society of Colon & Rectal Surgeons

Xanthelasma of colon

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Also called xanthoma, xanthomatous polyp, xanthogranulomatous inflammation

Very rare in colon; may clinically resemble polyp or carcinoma

Foamy cells without mucin

Foamy histiocytes common (40%) in rectal biopsies, but usually contain mucin (AJSP 2000;24:1009)

May be due to prior injury

Case reports: submucosal mass in sigmoid (Pathol Int 2005;55:440), intestinal xanthomas associated with xanthoma disseminatum (Dermatology 2004;208:164)

Micro: associated with surface hyperplastic change (APMIS 2004;112:3)

Positive stains: CD68

Negative stains: PAS-diastase, Alcian blue (pH 2.5 or 1.0), mucicarmine

DD: muciphages (positive mucin stains)

EM: electron-dense globules

End of Colon-nontumor chapter

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Table of contents

Non-neoplastic, non-congenital - adhesions, brown bowel, colchicine toxicity, colitis cystica profunda, gout, hyperplastic Pacinian corpuscle, idiopathic constipation, infracted epiploic appendages, reactive angioendotheliomatosis, xanthelasma

Normal anatomy of colon

Vasculature

Normal histology of colon

Normal physiology of colon

Atresia of colon

Duplication of colon

Heterotopia of colon

Hirschsprung’s disease of colon

Malrotation of colon

Diverticular disease of colon

Crohn’s disease of colon

Behcet’s syndrome of colon

History of chronic watery diarrhea and crampy abdominal pain with normal colonoscopy and barium enema

85% in elderly women, often smokers

Diverticular colitis

Graft versus host disease of colon

Malakoplakia of colon

Pouch related complications in colon

Typhlitis of colon

Balantidiasis of colon

Campylobacter jejuni of colon

Clostridium botulinum of colon

Escherichia coli of colon

Mycobacteria infections of colon other than tuberculosis

Rotavirus of colon

Salmonella of colon

Schistosomiasis of colon

Shigella of colon

Spirochetosis of colon

Syphilis of colon

Trichuriasis of colon

Tuberculosis of colon

Typhoid fever of colon

Vibrio cholera of colon

Yersinia infections of colon

Adhesions of colon

Amyloidosis of colon

Barium granuloma of colon

Colchicine toxicity of colon

Usually incidental

Commonly involves colonic wall (15% of cases), usually rectosigmoid or rectovaginal septum (Med Sci Monit 2000;6:787)

Florid vascular proliferation of colon

Gastric heterotopia of colon

Hyperplastic Pacinian corpuscle of colon

Solitary rectal ulcer syndrome

Vascular ectasia of colon

Vasculitis of colon

Volvulus of colon

Xanthelasma of colon