SMALL INTESTINE PATHOLOGY

MALABSORPTION AND SMALL BOWEL DISORDERS

• Autoimmune Enteropathy
• Celiac Disease
• Collagenous Sprue
• Common Variable Immunodeficiency
• Enteroendocrine Cell Dysgenesis
• Food Enteropathy
• Microvillus Inclusion Disease
• Tufting Enteropathy

COLITIS AND ENTERITIS

• Acute Self-limited Colitis
• Celiac Disease
• Chemical / Iatrogenic Colitis
• Collagenous Colitis
• Collagenous Sprue
• Crohn Disease
• Enterohemorrhagic O157:H7 E coli Colitis
• Eosinophilic Gastroenteritis
• Eosinophilic Proctocolitis
• Food Enteropathy
• Ischemic Colitis
• Incidental Chronic Colitis
• Lymphocytic Colitis
• Pseudomembranous Colitis
• Ulcerative Colitis
• Ulcerative Jejunoileitis

Autoimmune Enteropathy

• AKA generalized autoimmune gut disorder
• Gastrointestinal disease caused by autoimmune attack
• A disease of infants
  • First six months of life
• Rare in adults(with other autoimmune disorder)
  • Present as CD not responsive to gluten free diet
  • May be associated with thymoma
• Intractable diarrhea
• Non-responsive to TPN
• 30% mortality
• Extra-intestinal associations
  • IDMM
  • Hypothyroidism
  • Membranous glomerulonephritis
  • Sclerosing cholangitis
  • Autoimmune hepatitis
  • Coombs and hemolytic anemia
  • Other autoantibodies
    • Anti-mitochondrial antibody
    • Anti-nuclear antibody
    • Anti-parietal cell antibody
• Diagnostic Criteria
  • Principal involvement: duodenum, jejunum, stomach, +/- large intestine
  • No fissures or deep ulcers
  • Diffuse involvement of mucosa (no skip lesions)
  • Partial or complete villous atrophy
  • Crypts may be hyperplastic or destroyed
  • Inconspicuous to prominent apoptosis in crypts
  • Diffuse inflammation, but restricted to mucosa
  • Intraepithelial lymphocytes (IELs) mild to marked increase
  • Diffuse LP lymphocyte infiltrate
    • ↑CD3+ CD4+ alpha beta T cells
    • Prominent plasma cells
    • No granulomatous inflammation
    • Anti-enterocyte antibodies (anti-MCC2)
      • Indirect IF
      • Linear along brush border
      • Anti-goblet cell antibodies less specific
• DDx
  • Common variable immunodeficiency
    • Histologically indistinguishable from autoimmune enteropathy
    • Plasma cells markedly decreased
    • Prominent nodular lymphoid hyperplasia
    • Villous atrophy mild to severe
    • Crypt destruction not prominent
    • All antibodies depressed
    • Humoral testing not reliable
    • Food allergy
      • ↑Eosinophilic infiltrate
      • Associated allergy or atopy
      • Resolved by elimination of offending food from diet
      • Celiac disease
        • Usually occurs in childhood or older
        • Responds to gluten withdrawal
        • Anti-endomysial and – tissue transglutaminase antibodies
        • CD4 negative T cells predominate
        • Gamma delta T cell receptors predominate
      • Crohn disease
        • Skip lesions
        • Involves large intestine
        • Transmural inflammation
        • Granulomatous inflammation
        • Deep fissures frequent
      • Prolonged post-enteritis syndrome
      • Tropical sprue

CELIAC DISEASE

• Chronic enteritis secondary to gluten sensitivity
• AKA
  • Celiac sprue
  • Celiac disease
  • Gluten sensitive enteropathy
  • Non-tropical sprue
• Any age but mostly in childhood to 30s
• HLA linked, first degree relatives at 10x risk
• Childhood
  • Abdominal pain
  • Diarrhea
  • Steatorrhea
  • Weight loss
  • Growth retardation
• Adulthood (>45 yo)
  • Diarrhea not prominent
    • Abnormal malabsorption tests
    • Short stature
    • Infertility
    • Amenorrhea
    • Iron or folate deficiency
    • Osteoporosis
• Increased risk
  • Esophageal squamous carcinoma
  • Small intestinal carcinoma
  • Enteropathy type T cell lymphoma
    • Gamma-delta type
    • Aggressive
    • Gluten free diet can resolve or decrease risk
• Refractory sprue
  • Lack of clinical response to gluten free diet
  • Causes include
    • Failure to follow diet, intentionally or unintentionally
    • Development of collagenous sprue
    • Development of ulcerative jejunoileitis and enteropathy type T cell lymphoma
    • Wrong initial diagnosis
• Associated diseases
  • Dermatitis herpetiformis (DH)
    • 70-90% of DH patients have celiac disease
    • 10% of celiac disease patients have DH
    • Lymphocytic colitis
    • Collagenous colitis
    • Collagenous gastritis
    • Hyposplenism
    • Various autoimmune diseases
      • IDDM
      • Sjögren syndrome
      • Autoimmune liver disease
      • Autoimmune thyroiditis
      • Autoimmune myocarditis
      • SLE
• Clinicopathological diagnosis
• Biopsy required for diagnosis
  • Distal duodenum best
  • Avoids other inflammatory processes
• Microscopy
  • Villous atrophy in small intestine
    • Symptomatic patients total villous atrophy
      • Completely flattened villi
      • Variable, patchy, or partial atrophy common in pre-symptomatic or post-treatment patients
      • Increased IELs in small intestine
        • May be seen with or without atrophy
        • Cutoff varies by location
          • Duodenum >30 / 100 enterocytes

 

-   6-12 / 20 enterocytes at tips of villi

• Jejunum >40 / 100 enterocytes
• Occasionally in stomach and large intestine
• T cell phenotype
  • CD2+, CD3+, CD8 70-90%
  • Gamma delta T cell receptor
  • CD3 stain is useful for identification and counting
  • IEL evenly distributed from bottom to top of crypts or increased at tops
  • Normal IEL distribution decreases from bottom to top
  • Increased IELs without villus atrophy suggestive of latent/partially treated CD but not specific:
    • Infections

-  Helicobacter

-   Giardia

-   Cryptosporidium

-   Viruses

• Food allergy
• Drug reactions (NSAIDS)
• Immune system abnormalities
• Mixed chronic inflammatory infiltrate in LP
  • Plasma cells
  • Lymphocytes
  • Eosinophils
  • Neutrophils rare
    • Cryptitis/crypt abscesses suggest other diagnoses
    • Crypt hyperplasia
    • Mitotic figures may be numerous
    • Changes may be seen in stomach and large intestine
• Biopsy required to assess response to gluten restriction
  • Villous atrophy may be only partial or absent
  • IEL and LP infiltrate decreased or absent
  • Complete return to normal takes years
• Refractory sprue histology
  • Mucosal atrophy, thinning
  • Collagenous sprue
    • Increased subepithelial collagen layer
    • Ulcerative jejunoileitis
    • Decreased CD8 expression by T cells
    • Enteropathy type T cell lymphoma
• Modified Marsh Classification to grade CD
  • Grade A/Type 1: ↑IEL, no villous atrophy
  • Grade B1/Type 2: ↑IEL, villi present but shortened
  • Grade B2/Type 3: ↑IEL, complete villous atrophy
• IHC
  • CD3 or pan-T cell markers useful for counting T cells
• Serology Test Sensitivity Specificity
  • 3% of CD patients IgA deficient
  • IgG, IgA anti-gliadin antibody 70%, 97%
  • IgA anti-endomysial antibody 85-98%, 97-100%
  • IgA anti-tissue transglutaminase antibody 95-98%, 94-95%
• DDx
  • ↑IELs not specific
  • Tropical sprue
  • Prolonged post-enteritis syndrome
  • Autoimmune enteropathy
  • Common variable immunodeficiency
  • Food allergy
  • Crohn disease
  • Infections
    • Giardia
    • Helicobacter
    • Cryptosporidium
    • Viruses
    • Food allergy
    • Drug reactions (NSAIDS, chemotherapy)
    • Immune system abnormalities (GVHD, autoimmune enteropathy, other autoimmune diseases)

COLLAGENOUS SPRUE

• 22 to 84 yo
• Enteropathy demonstrating subepithelial collagen deposition combined with villous changes typical of celiac disease
• AKA refractory CD or sprue
• Diarrhea, malabsorption, weight loss
• Debate as to whether collagenous sprue a distinct entity
• Suggested that it represents a pattern of refractory CD
• Anti-endomysial antibody may be present
• Associations
  • Collagenous colitis 33%
  • Collagenous gastritis 15%
  • Lymphocytic gastritis 10%
  • Ulcerative jejunitis (1 of 12 cases)
• Variable response to steroids or gluten free diet
• Variable reports of prognosis and response to therapy
• Micro criteria
  • Irregular, thickened collagen layer below luminal BM
    • Normal BM 1-2 microns
    • > 10 microns thickness diagnostic
    • Envelops capillaries and inflammatory cells
    • Ragged interface with lamina propria
    • Trichrome useful for demonstration
    • Villous atrophy ranging from partial to total
    • Increased IELs in small intestine
      • >5 / 100 enterocytes
      • T cell phenotype
        • CD3+, CD8 variable
        • CD3 stain is useful for identification and counting
        • T cell clonality may be present
      • Chronic inflammatory infiltrate in lamina propria
        • Lymphocytes, plasma cells, eosinophils
      • Surface mucosa may detach
• DDx
  • Radiation
    • Diffuse fibrosis not just below BM
    • Scleroderma
      • Fibrosis also around crypts, may be diffuse
      • Artifact of sectioning

FOOD ENTEROPATHY

• Enteropathy caused by sensitivity to foods such as cow milk protein
• AKA
  • Allergic gastroenteropathy
  • Cow milk protein enteropathy
• < 12 months of age or on exposure to food in question
• Esophagus may show marked eosinophilic infiltrate
• Small intestine changes non-specific
  • Acute and chronic inflammation
  • Variable eosinophils
  • Variable villous atrophy
  • IELs increased but fewer than CD
• Diagnosis based on resolution following dietary restriction
• Foods
  • Cow milk most common
  • Breast milk
  • Soy protein
  • Egg
  • Wheat
• DDx
  • Eosinophilic gastroenteritis histologically indistinguishable, but excluded by age of onset and response to dietary restriction
  • Eosinophilic esophagitis and eosinophilic proctocolitis
    • Also frequently reactions to food allergy

MICROVILLUS INCLUSION DISEASE

• Hereditary neonatal diarrhea characterized by microvillus abnormalities
• AKA
  • Davidson syndrome
  • Familial enteropathy
  • Familial microvillous atrophy
• Rare, AR
• Severe intractable diarrhea in first week of life
  • Rarely as late as 60 days
• Microscopy
  • Severe villous atrophy
  • No crypt hyperplasia
  • No inflammation
  • PAS-D, polyclonal anti-CEA, CD10 stains highlight microvillus abnormalities in small intestine
    • Loss of brush border
    • Apical cytoplasmic positivity
    • May be recognizable as microlumina
• EM: loss of brush border and presence of apical cytoplasmic microlumina lined by microvilli
• DDx
  • Presentation at birth, lack of inflammation and presence of intracytoplasmic microlumina exclude other causes of villous atrophy and diarrhea

ACUTE SELF-LIMITED COLITIS

• Inflammation of colon due to infectious organisms, generally short term
• Diagnostic Criteria
  • Patchy or diffuse
  • Marked PMNs in superficial LP and crypts
    • PMNs in crypt epithelium (cryptitis)
    • PMNs in crypt lumens (crypt abscess)
    • Lacks chronic changes/architectural distortion of IBD
    • Mild crypt distortion with persistent, severe infections
    • Mild to no chronic inflammatory infiltrate in LP
    • Hemorrhage and thrombosis not typically seen
    • Ulceration, hemorrhage, Microscopythrombi in severe cases
• Common organisms
  • Campylobacter jejunalis
    • May have prominent macrophage infiltrate
    • Salmonella
      • Lacks mucus depletion except in severe cases
      • Prominent macrophage infiltrate with erythrophagocytosis
      • Shigella
        • Mucus depletion
        • Aphthous ulcers over prominent lymphoid follicles
        • Severe cases may ulcerate with a pseudomembrane
      • Yersinia
        • Aphthous ulcers
        • Necrotic granulomas/purulent granulomatous inflammation
        • Prominent follicular hyperplasia
• About half of cases have no identifiable bacterial cause
• Many such cases are viral
• Stool ova and parasite to rule out parasites
• SE(X)CSY
  • Salmonella
  • E. coli
    • Superficial mucosal necrosis
    • Frequent hemorrhage and capillary thrombosis
    • Campylobacter
    • Shigella
    • Yersinia

 

CHEMICAL IATROGENIC COLITIS

• History of recent endoscopy or foreign substance
• Disinfectant inadequately rinsed from colonoscope
  • Glutaraldehyde
• Presents within 48 hours
• Fever, chills, abdominal pain
• Diarrhea, blood per rectum
• Self-limited to 4-5 days
• May be caused by self-administered naturopathic enemas or other foreign substance
• Microscopy
  • Congestion and hemorrhage in mucosa
  • Microscopythrombi
  • Necrosis and sloughing of superficial mucosa
  • Pseudomembrane
• Differential Diagnosis of histology
  • E. coli O157:H7
  • Acute ischemic colitis
  • Nee clinical correlation

COMMON VARIABLE IMMUNODEFICIENCY SYNDROME

• 20-30 yo
• 10-25% familial
• AD, some AR
• 50% risk of carcinoma or lymphoma
• Upper and lower respiratory tract infections
• GI infections
  • Giardia
  • Salmonella
  • Campylobacter
  • Cryptosporidium
  • Cytomegalovirus
  • Esophagus
  • Candida
• AKA
  • Acquired hypogammaglobulinemia
  • Adult-onset hypogammaglobulinemia
  • Dysgammaglobulinemia
• Microscopy
  • Plasma cells markedly decreased 67%
  • Increased INTRAEPITHELIAL LYMPHOCYTES20-60%
    • Most prominent in stomach and small intestine
    • Variable villous blunting in small intestine with increased INTRAEPITHELIAL LYMPHOCYTESs
    • Predominantly T cells
    • Prominent lymphoid hyperplasia 50-80%
      • Most common in large intestine
      • Predominantly B cells aggregates
      • Single cell necrosis, increased apoptosis 10-50%
        • Most prominent in large intestine
      • Colonic changes
        • Variable crypt distortion  47%
        • Non-caseating granulomas 20%
        • Features of collagenous colitis 12%
      • Intraepithelial neutrophils suggest infection
• Differential Diagnosis
  • GVHD
  • Tropical sprue
  • Celiac disease
  • Autoimmune enteropathy
  • Food protein enteropathy
  • Crohn disease

 

SMALL AND LARGE INTESTINES

NORMAL

SB

-Villus/crypt: 3-5/1, normal to be shorter on Brunner or lymphoid aggregates, villus architecture hold together by MM

-4 consecutive normal villi means probably normal villous architecture.

-Intraepithelial lymphocytes: 1/5 enterocytes

-Enterocytes: brush border visible, basal nuclei

-Endocrine cells:

-Ganglion cells:

-Goblet cells:

Inflammatory cells:

Interstitial cells of Cajal:

M cells: flattened surface cells overlying lymphoid aggregates

Paneth cells: cecum and ascending colon

Undifferentiated crypt cells:

Brunner glands (duodenum)

 

LB

-Nonbranching

-LP contains lymph, plasma, eosinophils, histiocytes

-Submucosa usually non-inflammatory

-Scattered lymphoid follicles permitted, especially youngs

-Apoptosis in superficial LP. Abnormal in deep crypts (ischemia, CMV, chemoradiation, GVHD)

 

PROCESSING

-Orientation (less critical for LB)

-4-6 biopsies for each small bowel case

-H&E, PAS (screening for MAI and Whipple)

-and/-trichrome for collagenous sprue, trichrome for Giardia

 

CONGENITAL ABNORMALITIES

-Atresia

-Stenosis (SB)

-Heterotopia (pancreatic, gastric)

-Diverticulae (Meckel’s):

-Duplication (SB, LB)

-Enterogenous cysts (SB): due to notochord developmental problems, associated with vertebral anomalies

-Malrotation

-Omphalocele: membrane

-Gastroshisis: no membrane, surgical emergency

-Hirshsprung Disease

 

EMBRYOLOGY

heniation

rotation

reduction

descent

fixation

 

1. OMPHALOCELE

Def: abdominal musculature fails to formà herniated abdominal contents into ventral membranous sac through umbilical cord

2. GASTROSCHISIS

Def: abdominal musculature fails to formà herniated abdominal contents

-NO membranous sac

-NOT through umbilical cord

3. HIRSCHSPRUNG’S DISEASE OF COLON

-Male

-Sporadic, 10% have Down’s syndrome

Etio: inactivating RET mutationà no migration of neural crest cells to rectum, sometimes sigmoidà NO parasympathetic ganglion cells in submucosal and myenteric plexus

Ssx: no meconium, obstructive constipation

Gross: rectum small, no stool; functional obstruction and colonic dilation proximal to affected segment

Diagnosis

Full-thickness rectal biopsy (now suction biopsy is appropriate)

-Specimen adequacy (Steinberg p1517)

-No ganglion cells in submucosal or myenteric plexusesà serial sections needed and must exhaust entire block!

-Hypertrophy of MM and increased nonmyelinated nerve number and size

2. Frozen section (high error rate!)

-Identify ganglion cells

-Stain nerve fibres with acetylcholinesterase

3. Contrast enema and anorectal manometry

IHC: NSE and RET for ganglion cells

Types

Classic: aganglionic portion begins in distal colorectum and extends a considerable distance proximally

2. Ultrashort segment: ≤2cm in rectum/sigmoid

Short segment (90% cases): <40cm in rectum/sigmoid

Long segment: >40cm up to SB!

Zonal aganglionosis: “skip lesions”

 

4. MECKEL DIVERTICULUM

-20cm from ICV, antimesenteric

-Due to persistence of omphalomesenteric duct

-Obstruction, hemorrhage, perforation, diverticulitis, ulcer

Microscopy

-SB mucosa> pancreas, stomach tissues

 

5. DUPLICATION

-Partial or complete

-Usually in mesentery of LB or SB, can communicate with bowel lumen, no vertebral anomalies

Microscopy

-Organized SM, nerve plexus

 

MALABSORPTION (SMALL INTESTINE)

Biopsy site – proximal jejunum (distal to ligament of Treitz)

Defective intraluminal digestion

- digestion fats/proteins: pancreatic insufficiency due to pancreatitis or CF, ZES

- bile secretion (¯ fat solubilization): ileal dysfunction or resection with decreased bile salt uptake, cessation of bile flow (obstruction, hepatic dysfunction), nutrient preabsorption or modification by bacterial overgrowth

2) Abnormalities in terminal digestion

Transepithelial transport

Disaccharidase deficiency (lactose intolerance), bacterial overgrowth, abetalipoproteinemia, defects in ileal bile acid transporter

 

DIARRHEA

Secretory

Osmotic

Inflammatory

…

 

NODULES IN SMALL INTESTINE

-Pancreatic heterotopia: see stomach

-Brunner gland HP

 

BRUNNER GLAND HYPERPLASIA

-Branched tubuloalveolar, submucosal but can be above MM

Microscopy

-Brunner gland proliferation in proliferating SM.

-HP vs adenoma difficult

 

VILLOUS ATROPHY

-Kwashiorkor (protein deficiency, normal calories)

-Infectious enteritis (Giardia), ischemia

-Dermatitis herpetiformis (celiac disease)

-Celiac disease, CVID

-Allergy to proteins (chicken, soy, milk, egg, fish)

-Crohn disease

-Autoimmune enteropathy, Abetalipoproteinemia

-Sprue (Tropical, Whipple)

-Others: chemoradiation, megaloblastic anemia (can’t regenerate DNA), Microscopyvillous inclusion disease, stasis syndrome, mastocytosis,

 

ABETALIPOPROTEINEMIA

Inheritance: inborn error of met., AR

Symptoms: FTT, diarrhea, steatorrhea

Path: intestinal mucosal cells unable to synthesize apoprotein Bà FFA & monoglycerides cannot be assembled into chyloMicroscopynsà re-esterified to TG locally and stored in enterocytes causing lipid vacuolization

Lab:

-Lipid profile: no chyloMicroscopyns, no VLDL, no LDL

-Peripheral smear shows acantholytic red blood cells (Burr cells) due to lipid membrane abnormalities

Microscopy

-Enterocytes packed with fat vacuoles (“foamy”), especially at tips of villi

Positive stains: fat stains highlight lipid vacuoles

Differential Diagnosis

Megaloblastic anemia	Similar vacuolar change
Celiac
Tropical sprue

 

AGAMMAGLOBULINEMIC SPRUE (CVID)

-No plasma cells in lamina propria

 

CELIAC SPRUE

-Sensitivity to gluten (BROW), malabsorption, weight loss

-Improves following removal of gluten from diet

-Associated with lymphocytic colitis, DM I, Sjogren’s, AI thyroiditis

Path

-HLA haplotypes (DQa/b) upon exposure to BROW and triggered by adenovirusà abnormal cell mediated immunity (CD8 mostly)à Ab against gliadin (alcohol soluble moeity of gluten)à ¯ absorption

Diagnosis

-­ Abandhistologic findingsandimprovement following withdrawal of gluten

-Can only say “consistent with celiac sprue”

Complications

Enteropathy-associated T-cell lymphomaà think of this when patient does not respond to gluten withdrawal

SB adenocarcinoma

Dermatitis herpetiformis

DM I

Microscopy

-Overall thickness in the same

-Villous atrophy & crypt HP

-­ INTRAEPITHELIAL LYMPHOCYTES(>40/100), also plasma cells

-None/minimal acute inflammation

 

Labs: ­IgA, anti-gliadin, anti-reticulin, anti-endomyseal, anti-transgluataminase (best)

 

Differential Diagnosis

CVID
Other protein allergies
Infectious
Tropical sprue
ZES
Ischemia
Crohn
Duodenitis
Stasis

 

AUTOIMMUNE ENTEROPATHY

-crypt injury, anti-enterocyte antibodies, first 6 months of life

 

DISACCHARIDASE (LACTASE) DEFICIENCY

~located in apical cell

Congenital: rare; malabsorption with milkà explosive, watery stools and abdominal distention

Acquired: NA blacksà causes osmotic diarrhea

Diagnosis: ­ hydrogen in breath test(bacterial fermentation of undigested lactose)

Treatment: terminate milk and milk products

 

MICROVILLUS INCLUSION DISEASE

Clin: intractable watery diarrhea in infants, die by 2

Microscopy: atrophic villi with no inflammation, focal loss of BB

IHC: CD10 blush

EM: abnormal Microscopyvillus structures, intracytoplasmic inclusions lined by Microscopyvilli

 

PEPTIC DUODENITIS

Microscopy

-Acute and chronic inflammation, can be intraepithelial

-Villi blunting

-Erosions common

-Foveolar metaplasia (gastric metaplasia)

-Look for H pylori in antrum

Differential Diagnosis

-Gastric heterotopia: specialized glands

 

TROPICAL SPRUE

-Post-infectious sprue, in tropical countries

Symptoms: malabsorption within weeks of acute diarrheal enteric infection

Treatment: broad-spectrum antibiotics

Microscopy: variable villous atrophy (none, partial, total); injury to entire small bowel (not proximal as in celiac sprue), inflammatory infiltrate, crypt HP

 

LYMPHANGIECTASIA

-Focal or diffuse

-Sometimes protein-losing enteropathy (hypoAlb, edema, lymphocytopenia).

Etio

-Primary: kids

-Secondary: retroperitoneal fibrosis, pancreatitis, constrictive pericarditis, primary myocardial disease, intestinal Behcet, sarcoidosis, Waldenstrom,

Microscopy

-Dilated lymphatics, otherwise normal tissue

INFECTIONS

Granulomas in infections

-Viral:

-Bacterial: syphilis, chlamydia, Yersinia

-Mycobacterial: TB, salmonella, campylobacter

-Fungal:

-Parasitic:

 

1. WHIPPLE DISEASE

-Diarrhea, malabsorption,

Etio: Trepheryma whipplei (rod)

Gross: shaggy, edematous

Microscopy

-Mild blunted villi

-FAT globules (actually distended lacteal) among sheets of foamy histocytes

-DPASand granules in macrophagesà quite large

IHC

-Ab anti-Whipple, PCR, EM,

Treatment: antibiotics

Differential Diagnosis

MAI, malakoplakia, muciphages (macrophages containing mucin), mineral oil ingestion

MAI	Also PASand granules but AFBand/ZNand
Histoplasmosis	Blue dots surrounded by halo, silver or PASand show yeasts
Malakoplakia
Muciphages
Mineral oil ingestion

2. GIARDIA LAMBLIA

Clin: malabsorption, chronic diarrhea

-Stomach, colon possible

Diagnosis: detect cysts, trophozoites or antigens in stool

Microscopy:

-Variable villous blunting, ↑chronic inflammation.

-Giardia: pear shaped with 2 nuclei, 4 flagellae, in lumen

Stains: Giemsa, trichrome

 

3. E. COLI

Types

-Enterohemorrhagic (O157:H7): hamburgerà bloody diarrheaà HUS/TPP. Ischemic type change

-Enteroinvasive:

-Enterotoxigenic: no change

-Enteropathogenic:

-Enteroaggressive:

-Enteroadherent: Gram- adherent organisms

 

4. PSEUDOMEMBRANOUS COLITIS

Etio: acute colitis following broad spectrum antibioticsà favor the overgrowth of Clostridium difficile over other gut bacteria, often in elderly

Path: C. difficileà produces exotoxin A and B binds to receptors on cells and inactivate the RhO family of cytoplasmic proteinsà Microscopyfilament disassociation and cell retraction

-exotoxin Aà intestinal secretion and acute inflammation

Symptoms: acute or chronic diarrhea; toxic megacolon; perforation

Px: most respond to tx. (Flagyl) (25% relapse)

Diagnosis:  C. diff toxin A or B (less common) assay in stool

Gross: yellow-white mucosal plaques®bleed when scraped

Microscopy

-Patchy superficial epithelial necrosis, focal active colitis (crypt abscesses, cryptitis)à “volcano” fibrino-purulent necrotic debris from cryptsà complete crypt necrosis indistinguishable from ischemic colitis

-LPà dense nf, cap. fibrin thrombi

Differential Diagnosis

E. coli O157:H7

2. Shigella

3. Ischemic colitis

C difficile	Ischemic	Infectious
Volcano	Hyaline fibrosis
	Few inflammation

5. SPIROCHETOSIS

Location: colon, appendix

Microscopy: fuzzy luminal border

SS: Warthin Starry, AB, PAS

 

6. ACTINOMYCES

Gross: lg, ulcerated mass

Microscopy: sulfur granules, filamentous bacteria

SS: Gramand

7. ENTAMOEBA

flask shaped ulcer

Microscopy: ulcer and org. foamy cytoplasm, eccentric nucleus(with ingestion of RBC)

 

8. MALAKOPLAKIA

Gross: thick mucosa and submucosa

Microscopy: ­ hf w/ MG bodies

Differential Diagnosis: foamy cells Differential Diagnosis

 

9. CMV

Gross: punched out ulcers

Microscopy: cryptitis, PMN, ulcer,

CMV: lg cells with smudgy nuclear and cytoplasmic inclusionsà stromal and endothelials

W/U: multiple levels and IHC CMV

 

10. HSV

Gross: mult. confluent ulcers

Microscopy: 3M’s at ulcer edge, ground glass nuclei

W/U: multiple levels and IHC HSV

 

11. CRYPTOCOCCUS:

Spherical with halo which is PAS and mucicarmine and

 

12. MUCORMYCOSIS:

Clear hyphae, no septae, wide branches

 

13. ASPERGILLUS:

Septae, 45 degree branching

 

14. ENTAMOEBA HISTOLYTICA:

Tropical countries. Colon and cecum. Flask-shaped ulcers, resembles macrophages (foamy cytoplasm with perfect purple round eccentric small nucleus), look for eaten RBCs. Always look for this in acute fibrinoinflammatory exudate at ulcer base

15. ENTEROBIUS VERMICULARIS (pinworms):

Has 2 little side thorns

 

16. STRONGYLOIDES:

Worms with pointy tails

 

17. ACTINOMYCOSIS:

Sulfur granules

 

18. YERSINIA:

Right colon, appendix and ileum over lymphoid follicles. Necrotizing granulomas (also mesenteric LN), G- bacilli.

 

19. SALMONELOSIS:

From food-poisoning to enteric fever (typhoid) in neutropenic. Terminal ileum over lymphoid follicles. Histiocytes with erythrophagocytosis, only minimal PMN

 

20. SCHISTOSOMIASIS:

Colitis to bowel obstruction. Eggs

 

AIDS-RELATED INFLAMMATORY DISEASES

-Adenovirus, CMV, Cryptosporidium, Histo, Giardia, Histoplasma, MAI, KS, E histolytica, Candida, spirochetosis

Microscopy: focal apoptosis deep in colonic crypts

Differential Diagnosis: graft vs. host disease, bowel prep

 

1. CRYPTOSPORIDIOSIS

-Self-limited in immunocompetent but severe explosive watery diarrhea resistant to most therapy in HIVand

-In SB mostly

Diagnosis: acid-fast infective oocyst in stool

Microscopy

-2-5μm basophilic dots attached to surface

-Variable villus changes, eosinophils

Positive stains: Giemsa, silver stains, PAS

DD: mucin, cellular debris

 

 

2. MICROSCOPYSPORIDIA

-Associated with immunosuppression, HIV

Diagnosis: stool examination, PCR

Microscopy: minimal/no changes in mucosa

-Spores: 1.5mm dots inside enterocytes; may be surrounded by halos

-Nucleated sporont: 3-5μm, rounded, basophilic, often surrounded by a halo

Positive stains: Giemsa

EM: helpful in dx

 

3. ISOSPORA

-Proximal SB

Microscopy

-Variable villous blunting

-Ovoid organisms inside and beneath enterocytes

 

4. MYCOBACTERIUM AVIUM INTRACELLULARE MAI

-Associated with HIV

Location: SB normal?

Diagnosis: blood or stool cultures

Microscopy

-Foamy macrophages with cytoplasmic bacillary rods in LP

-Mminimal inflammation

Differential Diagnosis: Whipple’s disease but without fat vacuoles

Positive stains: FAFB, ZN

MAI	Whipple
Patchy	Diffuse
PASand (bacilli), AFBand, ZNand	PASand (large granules)
No	Fat vacuoles

5. TUBERCULOSIS

-associated with HIV

Loc: ileocecal

Microscopy: caseating or noncaseating granulomas, ulceration and desmoplasia

Positive stains: FAFB, ZN

INFLAMMATORY CONDITIONS

DUODENAL PEPTIC ULCER

Clinical: H. pylori, ZES, smoking

Pathophysiology: gastric acid hypersecretion (balance between aggressive factors and defensive factors→see stomach)

Gross:

-punched out lesion (well defined margins)

-multiple lesions -> think ZES

Microscopy:

-abrupt lesions with normal adjacent mucosa

-gastric metaplasia

-chronic duodenitis

-Brunner’s gland hyperplasia

-H. pylori often present

 

References:

1. Robbins & Cotran Pathologic Basis of Disease, 8th edition. Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Nelson Fausto, MD; Jon Aster, MD. Saunders. Published June 2009.

2. Sternberg’s Diagnostic Surgical Pathology, 5th edition. Darryl Carter, Joel K. Greenson, Victor E. Reuter , Mark H. Stoler. Lippincott Williams & Wilkins. Published Aug 26 2009.

3. College of American Pathologists Cancer Protocols and Checklists:

http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr